Cancer Research and Treatment

Original Articles

Breast cancer

Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes: Xin Li, Zehao Li, Lin Li, Tong Liu, Cheng Qian, Yanlv Ren, Zhigao Li, Kejin Chen, Dongchen Ji, Ming Zhang, Jinsong Wang; Cancer Res Treat. 2024;56(1):134-142. Published online August 14, 2023; DOI: https://doi.org/10.4143/crt.2023.652

Purpose
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

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FDA-approved drugs containing dimethylamine pharmacophore: a review of the last 50 years
Sandeep Bindra, Kuntal Bose, Amrutha Chandran Thekkantavida, Della Grace Thomas Parambi, Tariq G. Alsahli, Manu Pant, Leena K. Pappachen, Hoon Kim, Bijo Mathew
RSC Advances.2024; 14(38): 27657. CrossRef

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Gastrointestinal cancer

FGFR4 Gly388Arg Polymorphism Affects the Progression of Gastric Cancer by Activating STAT3 Pathway to Induce Epithelial to Mesenchymal Transition: Yanwei Ye, Jie Li, Dongbao Jiang, Jingjing Li, Chuangfeng Xiao, Yingze Li, Chao Han, Chunlin Zhao; Cancer Res Treat. 2020;52(4):1162-1177. Published online May 25, 2020; DOI: https://doi.org/10.4143/crt.2020.138

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Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays a critical role in cancer progression involving in tumor proliferation, invasion, and metastasis. This study clarified the role of FGFR4-Arg388 variant in gastric cancer (GC), and more importantly highlighted the possibility of this single nucleotide polymorphism (SNP) as potential therapeutic targets.
Materials and Methods
FGFR4 polymorphism was characterized in advanced GC patients to perform statistical analysis. FGFR4-dependent signal pathways involving cell proliferation, invasion, migration, and resistance to oxaliplatin (OXA) in accordance with the SNP were also assessed in transfected GC cell lines.
Results
Among 102 GC patients, the FGFR4-Arg388 patients showed significantly higher tumor stage (p=0.047) and worse overall survival (p=0.033) than the Gly388 patients. Immunohistochemical results showed that FGFR4-Arg388 patients were more likely to have higher vimentin (p=0.025) and p-STAT3 (p=0.009) expression compared with FGFR4-Gly388 patients. In transfected GC cells, the overexpression of FGFR4-Arg388 variant increased proliferation and invasion of GC cells, increasing resistance of GC cells to OXA compared with cells overexpressing the Gly388 allele.
Conclusion
The exploration mechanism may be through FGFR4-Arg388/STAT3/epithelial to mesenchymal transition axis regulating pivotal oncogenic properties of GC cells. The FGFR4-Arg388 variant may be a biomarker and a candidate target for adjuvant treatment of GC.

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Schlafen 11 predicts response to platinum-based chemotherapy in gastric cancers
Tsuyoshi Takashima, Daiki Taniyama, Naoya Sakamoto, Maika Yasumoto, Ryuichi Asai, Takuya Hattori, Ririno Honma, Pham Quoc Thang, Shoichi Ukai, Ryota Maruyama, Kenji Harada, Kazuya Kuraoka, Kazuaki Tanabe, Atsuo T. Sasaki, Hideki Ohdan, Eiichi Morii, Junko
British Journal of Cancer.2021; 125(1): 65. CrossRef
FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
Jung Han Kim, Soo Young Jeong, Hyun Joo Jang, Sung Taek Park, Hyeong Su Kim
Frontiers in Oncology.2021;[Epub] CrossRef
FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
Cancers.2021; 13(22): 5796. CrossRef

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Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy: Jie Yang, Ying Huang, Yanru Feng, Hongmin Li, Ting Feng, Jinna Chen, Luxi Yin, Weihu Wang, Shulian Wang, Yueping Liu, Yongwen Song, Yexiong Li, Jing Jin, Wen Tan, Dongxin Lin; Cancer Res Treat. 2019;51(3):1198-1206. Published online December 26, 2018; DOI: https://doi.org/10.4143/crt.2018.527

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Purpose
Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT).
Materials and Methods
Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model.
Results
The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer.
Conclusion
These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.

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CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells, pulmonary microvascular endothelial cells, and pericytes under hypoxia
Xiaoyi Hu, Shang Wang, Hui Zhao, Yaqin Wei, Ruowang Duan, Rong Jiang, Wenhui Wu, Qinhua Zhao, Sugang Gong, Lan Wang, Jinming Liu, Ping Yuan
Animal Models and Experimental Medicine.2024; 7(3): 310. CrossRef
Systematic Review of Genetic Polymorphisms Associated with Acute Pain Induced by Radiotherapy for Head and Neck Cancers
Vivian Salama, Yimin Geng, Jillian Rigert, Clifton D. Fuller, Sanjay Shete, Amy C. Moreno
Clinical and Translational Radiation Oncology.2023; 43: 100669. CrossRef
Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy
Alexandra Giatromanolaki, Christos Kavazis, Anastasia G. Gkegka, Maria Kouroupi, Alexandra Tsaroucha, Michael Pitiakoudis, Michael I. Koukourakis
Immunobiology.2023; 228(6): 152756. CrossRef
SYVN1‐mediated ubiquitination and degradation of MSH3 promotes the apoptosis of lens epithelial cells
Xiaojuan Chen, Guowei Zhang, Pengfei Li, Jianfeng Yu, Lihua Kang, Bai Qin, Ying Wang, Jian Wu, Yong Wang, Junfang Zhang, Miaomiao Qin, Huaijin Guan
The FEBS Journal.2022; 289(18): 5682. CrossRef
Dietary methyl donor nutrients, DNA mismatch repair polymorphisms, and risk of colorectal cancer based on microsatellite instability status
Jimi Kim, Jeonghee Lee, Jae Hwan Oh, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim, Hee Jin Chang
European Journal of Nutrition.2022; 61(6): 3051. CrossRef
Identification of a novel germline frameshift mutation p.D300fs of PMS1 in a patient with hepatocellular carcinoma
Xiaobin Li, Yuling Wu, Peisu Suo, Guifeng Liu, Lifeng Li, Xiaoni Zhang, Shifu Chen, Mingyan Xu, Lele Song
Medicine.2020; 99(5): e19076. CrossRef
Potential Functional Variants in DNA Repair Genes Are Associated with Efficacy and Toxicity of Radiotherapy in Patients with Non-Small-Cell Lung Cancer
Zhiguang Yang, Zhaoyu Liu
Journal of Oncology.2020; 2020: 1. CrossRef
Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants
Luís S. Santos, Octávia M. Gil, Susana N. Silva, Bruno C. Gomes, Teresa C. Ferreira, Edward Limbert, José Rueff
Genes.2020; 11(9): 1083. CrossRef

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Effects of Soy Product Intake and Interleukin Genetic Polymorphisms on Early Gastric Cancer Risk in Korea: A Case-Control Study: Sarah Yang, Yoon Park, Jeonghee Lee, Il Ju Choi, Young Woo Kim, Keun Won Ryu, Joohon Sung, Jeongseon Kim; Cancer Res Treat. 2017;49(4):1044-1056. Published online January 19, 2017; DOI: https://doi.org/10.4143/crt.2016.515

Abstract PDF Supplementary Material PubReader ePub

Purpose
The current study investigated whether the combined effects of soy intake and genetic polymorphisms of interleukin (IL) genes modify gastric cancer risk.
Materials and Methods
A total of 377 cases and 754 controls of Korean origin were included in the analysis. Soy consumption was assessed using a semi-quantitative food frequency questionnaire. Seven variants of IL10 (rs1800871), IL2 (rs2069763 and rs2069762), IL13 (rs6596090 and rs20541), and IL4R(rs7205663 and rs1805010) were genetically analyzed. To analyze the combined effect of soy intake and genetic polymorphisms, a low-intake group and high-intake group of each type of soy were categorized based on the intake level of the control group. Interactions between soy products and these genetic variants were analyzed by a likelihood ratio test, in which a multiplicative interaction term was added to the logistic regression model.
Results
A higher intake of nonfermented soy products was associated with a reduced cancer risk (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.43 to 0.90), and the reduced risk was only apparent in males (OR, 0.44; 95% CI, 0.27 to 0.71). None of the IL genetic polymorphisms examined were independently associated with gastric cancer risk. Individuals with a minor allele of IL2 rs2069762 and a higher intake of nonfermented soy food had a decreased risk of gastric cancer (OR, 0.46; 95% CI, 0.31 to 0.68) compared to those with a lower intake (p_interaction=0.039).
Conclusion
Based on the genetic characteristics of the studied individuals, the interaction between IL2 rs2069762 and nonfermented soy intake may modify the risk of gastric cancer.

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Polyphenol intake and gastric cancer: A case-control study in the Brazilian Amazon region
Marcela de Araújo Fagundes, Renata Alves Carnauba, Gisele Aparecida Fernandes, Paulo Pimentel de Assumpção, Maria Paula Curado
Cancer Epidemiology.2024; 88: 102518. CrossRef
Oral Microbiota as a Diagnostic Biomarker of Digestive Cancer: A Systematic Review
SK Aziz Ikbal, Surendra Kumar Yadav, Roopanshi Mehrotra, Tasneem Fatima, Anjusha Sharda, Srashti Gupta
The Journal of Contemporary Dental Practice.2024; 24(11): 902. CrossRef
The pertinence of gastric cancer and interleukin 10–819 single nucleotide polymorphisms: a meta-analysis and systematic review
Qianqian Mao, Yanwen Liu, Xi Chen, Cheng Jiang Liu
BMC Gastroenterology.2024;[Epub] CrossRef
Soy Product Consumption and the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies
Chenting Wang, Keqing Ding, Xuanzhen Xie, Jinyue Zhou, Pengju Liu, Shuang Wang, Ting Fang, Guozhang Xu, Chunlan Tang, Hang Hong
Nutrients.2024; 16(7): 986. CrossRef
Interaction between dietary potassium intake and TNF-α rs1800629 genetic polymorphism in gastric cancer risk: a case–control study conducted in Korea
Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
British Journal of Nutrition.2023; 130(5): 887. CrossRef
Association between soy products, fruits, vegetables, and dairy products and gastric cancer risk in Helicobacter pylori-infected subjects: a case-control study in Korea
Jung Hyun Kwak, Chang Soo Eun, Dong Soo Han, Yong Sung Kim, Kyu Sang Song, Bo Youl Choi, Hyun Ja Kim
Nutrition Research and Practice.2023; 17(1): 122. CrossRef
Dietary intake and cancer incidence in Korean adults: a systematic review and meta-analysis of observational studies
Ji Hyun Kim, Shinyoung Jun, Jeongseon Kim
Epidemiology and Health.2023; : e2023102. CrossRef
The association of dietary fibre intake and the IL13 rs20541 polymorphism with the risk of gastric cancer: a case-control study in Korea
Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
European Journal of Clinical Nutrition.2022; 76(7): 1031. CrossRef
Dietary Polyphenol Intake and Gastric Cancer: A Systematic Review and Meta-Analysis
Marcela de Araújo Fagundes, Alex Richard Costa Silva, Gisele Aparecida Fernandes, Maria Paula Curado
Cancers.2022; 14(23): 5878. CrossRef
Sex-dependent associations between MAP3K1 gene polymorphisms and soy products with the gastric cancer risk in Korea: a case-control study
Jung Hyun Kwak, Chang Soo Eun, Dong Soo Han, Yong Sung Kim, Kyu Sang Song, Bo Youl Choi, Hyun Ja Kim
BMC Gastroenterology.2022;[Epub] CrossRef
Dietary patterns and gastric cancer risk in a Korean population: a case–control study
Ji Hyun Kim, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
European Journal of Nutrition.2021; 60(1): 389. CrossRef
Possible Roles of Interleukin-4 and -13 and Their Receptors in Gastric and Colon Cancer
Xujun Song, Benno Traub, Jingwei Shi, Marko Kornmann
International Journal of Molecular Sciences.2021; 22(2): 727. CrossRef
The association between soy‐based food and soy isoflavone intake and the risk of gastric cancer: a systematic review and meta‐analysis
Yameng Wang, Jiaping Guo, Fei Yu, Yongmei Tian, Yongjun Wu, Lingling Cui, Li‐e Liu
Journal of the Science of Food and Agriculture.2021; 101(13): 5314. CrossRef
The Associations of Dietary Iron Intake and the Transferrin Receptor (TFRC) rs9846149 Polymorphism with the Risk of Gastric Cancer: A Case–Control Study Conducted in Korea
Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
Nutrients.2021; 13(8): 2600. CrossRef
Identification of Dietary Pattern Networks Associated with Gastric Cancer Using Gaussian Graphical Models: A Case-Control Study
Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Jeongseon Kim
Cancers.2020; 12(4): 1044. CrossRef
Genome‐wide profiling of normal gastric mucosa identifies Helicobacter pylori‐ and cancer‐associated DNA methylome changes
Hae Dong Woo, Nora Fernandez‐Jimenez, Akram Ghantous, Davide Degli Esposti, Cyrille Cuenin, Vincent Cahais, Il Ju Choi, Young‐Il Kim, Jeongseon Kim, Zdenko Herceg
International Journal of Cancer.2018; 143(3): 597. CrossRef
The association between dietary isoflavones intake and gastric cancer risk: a meta-analysis of epidemiological studies
Jie You, Yafei Sun, Yacong Bo, Yiwei Zhu, Dandan Duan, Han Cui, Quanjun Lu
BMC Public Health.2018;[Epub] CrossRef

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FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition: Sang Hee Cho, Chang Soo Hong, Hee Nam Kim, Min Ho Shin, Ka Rham Kim, Hyun Jeong Shim, Jun Eul Hwang, Woo Kyun Bae, Ik Joo Chung; Cancer Res Treat. 2017;49(3):766-777. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.457

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patientswith resected colon cancer, including the underlying mechanism.
Materials and Methods
FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.
Results
Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.
Conclusion
The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

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Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment
Alessandro Ottaiano, Mariachiara Santorsola, Monica Ianniello, Anna Ceccarelli, Marika Casillo, Francesco Sabbatino, Nadia Petrillo, Marco Cascella, Francesco Caraglia, Carmine Picone, Francesco Perri, Roberto Sirica, Silvia Zappavigna, Guglielmo Nasti, G
Journal of Translational Medicine.2024;[Epub] CrossRef
Comprehensive analysis of the prognostic value and immune infiltration of FGFR family members in gastric cancer
Chengcheng Yang, Dingli Song, Fengyu Zhao, Jie Wu, Boxiang Zhang, Hong Ren, Qi Sun, Sida Qin
Frontiers in Oncology.2022;[Epub] CrossRef
Inhibition of FGF‐FGFR and VEGF‐VEGFR signalling in cancer treatment
Guihong Liu, Tao Chen, Zhenyu Ding, Yang Wang, Yuquan Wei, Xiawei Wei
Cell Proliferation.2021;[Epub] CrossRef
Every breath you take: Impacts of environmental dust exposure on intestinal barrier function–from the gut-lung axis to COVID-19
Meli’sa S. Crawford, Tara M. Nordgren, Declan F. McCole
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(4): G586. CrossRef
FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
Jung Han Kim, Soo Young Jeong, Hyun Joo Jang, Sung Taek Park, Hyeong Su Kim
Frontiers in Oncology.2021;[Epub] CrossRef
FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
Cancers.2021; 13(22): 5796. CrossRef
Fibroblast growth factor receptor 4 increases epidermal growth factor receptor (EGFR) signaling by inducing amphiregulin expression and attenuates response to EGFR inhibitors in colon cancer
Chang‐Soo Hong, Eun‐Gene Sun, Ji‐Na Choi, Dae‐Hwan Kim, Jo‐Heon Kim, Kyung‐Hyun Ryu, Hyun‐Jeong Shim, Jun‐Eul Hwang, Woo‐Kyun Bae, Hyeong‐Rok Kim, Kyung Keun Kim, Chaeyong Jung, Ik‐Joo Chung, Sang‐Hee Cho
Cancer Science.2020; 111(9): 3268. CrossRef
Mahanine induces apoptosis, cell cycle arrest, inhibition of cell migration, invasion and PI3K/AKT/mTOR signalling pathway in glioma cells and inhibits tumor growth in vivo
Maohua Chen, Xiangqian Yin, Chuan Lu, Xiandong Chen, Huajun Ba, Jianyong Cai, Jun Sun
Chemico-Biological Interactions.2019; 299: 1. CrossRef
Fibroblast growth factor receptor 4 (FGFR4) as detected by immunohistochemistry is associated with postoperative residual disease in ovarian cancer
Sabine Heublein, Michael S. Anglesio, Frederik Marmé, Stefan Kommoss
Journal of Cancer Research and Clinical Oncology.2019; 145(9): 2251. CrossRef
TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma
Woo-Kyun Bae, Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Ji-Hee Lee, Keunsoo Kang, Kyung-Hyun Ryu, Hyun-Jeong Shim, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung
Cancer Letters.2018; 415: 106. CrossRef
The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction
Álvaro Quintanal-Villalonga, Laura Ojeda-Márquez, Ángela Marrugal, Patricia Yagüe, Santiago Ponce-Aix, Ana Salinas, Amancio Carnero, Irene Ferrer, Sonia Molina-Pinelo, Luis Paz-Ares
Scientific Reports.2018;[Epub] CrossRef
Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients
Lu Chen, Huijie Qi, Liudi Zhang, Haixia Li, Jie Shao, Haifei Chen, Mingkang Zhong, Xiaojin Shi, Ting Ye, Qunyi Li
BMC Cancer.2018;[Epub] CrossRef

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DNA Methyltransferase Gene Polymorphisms for Prediction of Radiation-Induced Skin Fibrosis after Treatment of Breast Cancer: A Multifactorial Genetic Approach: Salvatore Terrazzino, Letizia Deantonio, Sarah Cargnin, Laura Donis, Carla Pisani, Laura Masini, Giuseppina Gambaro, Pier Luigi Canonico, Armando A. Genazzani, Marco Krengli; Cancer Res Treat. 2017;49(2):464-472. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.256

Abstract PDF PubReader ePub

Purpose
This study was conducted to investigate the role of four polymorphic variants of DNA methyltransferase genes as risk factors for radiation-induced fibrosis in breast cancer patients. We also assessed their ability to improve prediction accuracy when combined with mitochondrial haplogroup H, which we previously found to be independently associated with a lower hazard of radiation-induced fibrosis.
Materials and Methods
DNMT1 rs2228611,DNMT3A rs1550117,DNMT3A rs7581217, and DNMT3B rs2424908 were genotyped by real-time polymerase chain reaction in 286 Italian breast cancer patients who received radiotherapy after breast conserving surgery. Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue–Subjective Objective Management Analytical (LENT-SOMA) scale. The discriminative accuracy of genetic models was assessed by the area under the receiver operating characteristic curves (AUC).
Results
Kaplan-Meier curves showed significant differences among DNMT1 rs2228611 genotypes in the cumulative incidence of grade ≥ 2 subcutaneous fibrosis (log-rank test p-value= 0.018). Multivariate Cox regression analysis revealed DNMT1 rs2228611 as an independent protective factor for moderate to severe radiation-induced fibrosis (GG vs. AA; hazard ratio, 0.26; 95% confidence interval [CI], 0.10 to 0.71; p=0.009). Adding DNMT1 rs2228611 to haplogroup H increased the discrimination accuracy (AUC) of the model from 0.595 (95% CI, 0.536 to 0.653) to 0.655 (95% CI, 0.597 to 0.710).
Conclusion
DNMT1 rs2228611 may represent a determinant of radiation-induced fibrosis in breast cancer patients with promise for clinical usefulness in genetic-based predictive models.

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DNMT3A and DNMT3B in Breast Tumorigenesis and Potential Therapy
Xiaxia Man, Qi Li, Baogang Wang, He Zhang, Songling Zhang, Ziyi Li
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1

Chunlin Zhang, Jiaoping Mi, Yuan Deng, Zeyi Deng, Dan Long, Zhaohui Liu
OncoTargets and Therapy.2020; Volume 13: 4201. CrossRef
Betulinic Acid and Brosimine B Hybrid Derivatives as Potential Agents against Female Cancers
Nádia M. Garcês de Couto, Júlia B. Willig, Thaís C. Ruaro, Diogo Losch de Oliveira, Andréia Buffon, Diogo A. Pilger, Mara S.P. Arruda, Diogo Miron, Aline R. Zimmer, Simone C.B. Gnoatto
Anti-Cancer Agents in Medicinal Chemistry.2020; 20(5): 622. CrossRef
Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis
Shashank Shrishrimal, Elizabeth A. Kosmacek, Rebecca E. Oberley-Deegan
Oxidative Medicine and Cellular Longevity.2019; 2019: 1. CrossRef
Impact of ATM rs1801516 on late skin reactions of radiotherapy for breast cancer: Evidences from a cohort study and a trial sequential meta-analysis
Salvatore Terrazzino, Sarah Cargnin, Letizia Deantonio, Carla Pisani, Laura Masini, Pier Luigi Canonico, Armando A. Genazzani, Marco Krengli, Christophe Badie
PLOS ONE.2019; 14(11): e0225685. CrossRef
Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population
Jennifer J. Hu, James J. Urbanic, L. Doug Case, Cristiane Takita, Jean L. Wright, Doris R. Brown, Carl D. Langefeld, Mark O. Lively, Sandra E. Mitchell, Anu Thakrar, David Bryant, Kathy Baglan, Jon Strasser, Luis Baez-Diaz, Glenn J. Lesser, Edward G. Shaw
Journal of Clinical Oncology.2018; 36(24): 2473. CrossRef

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Genetic Variations of Drug Transporters Can Influence on Drug Response in Patients Treated with Docetaxel Chemotherapy: Jung Ran Choi, Jeong-Oh Kim, Dae Ryong Kang, Jung-Young Shin, Xiang Hua Zhang, Ji Eun Oh, Ji-Young Park, Kyoung-Ah Kim, Jin-Hyoung Kang; Cancer Res Treat. 2015;47(3):509-517. Published online December 16, 2014; DOI: https://doi.org/10.4143/crt.2014.012

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Purpose
Dose-limiting toxicities of docetaxel are widely considered to be neutropenia, anemia, skin toxicity, and nausea. One of the factors that limit the use of docetaxel is its unpredictability of inter-individual variation in toxicity. Materials and Methods In order to identify the genetic factors that affect the risk of docetaxel-induced toxicities, we recruited patients who received docetaxel chemotherapy. We genotyped 92 patients with single-nucleotide polymorphisms (SNPs) in 5 genes: CYP3A4 (CYP3A4*1B, CYP3A4*18, and CYP3A4*3), CYP3A5 (CYP3A5*2 and CYP3A5*3), ABCB1 (C1236T, G2677G/T, and C3435T), SLCO1B3 (rs11045585), and ABCC2 (rs12762549). Results Out of 92 patients, 70 had grade 3 or 4 neutropenia; 4 had grade 1 or 2; and 18 had no toxicity (76.1%, 4.3%, and 19.6%, respectively). The findings of the SNP analysis showed that patients with TT genotype of ABCB1 3435C>T polymorphism showed significantly higher risk of neutropenia and anemia (p=0.029 and p=0.044, respectively). There were significant associations between docetaxel-induced leucopenia and 2677G/T of ABCB1 and rs12762549 of ABCC2 (p=0.025 and p=0.028, respectively). In a multivariate analysis, we observed that patients carrying 2677G>T in ABCB1might be associated with higher risk of chemo-resistance when treated with docetaxel (odds ratio [OR], 6.48; confidence interval, 1.92 to 21.94; p=0.003). In a subgroup analysis of non-small cell lung cancer patients, a significant association of tumor response with G2677T/A (OR, 4.54) in ABCB1 and SLCO1B3 (OR, 9.44) was observed. Conclusion Our data suggest that ABCB1 (2677G/T) and SLCO1B3 (rs11055585) might be major genetic predictors of docetaxel-related toxicities in patients receiving docetaxel chemotherapy

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Polymorphism of Transporter Genes Contributes to Variations in Treatment Outcomes and Adverse Events in Platinum Based- Chemotherapy- Treated Oral Cancer Patients
Pranab Kumar Sahoo, Tanuma Mistry, Sushmita Ghosh, Ranita Pal, Sutapa Mahata, Sinjini Sarkar, Trisha Choudhury, Sriparna Datta, R Suresh Kumar, Anup Kumar Bhowmick, Partha Nath, Kalyan Kusum Mukherjee, Vilas D. Nasare
Precision Oncogenomics.2024;[Epub] CrossRef
The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment
Xinyu Wu, Huihua Xiong
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Parul Sharma, Navneet Singh, Siddharth Sharma
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Effects of Polymorphisms of Innate Immunity Genes and Environmental Factors on the Risk of Noncardia Gastric Cancer: Jeongseon Kim, Young Ae Cho, Il Ju Choi, Yeon-Su Lee, Sook-Young Kim, Jung-Ah Hwang, Soo-Jeong Cho, Myeong-Cherl Kook, Chan Gyoo Kim, Young-Woo Kim; Cancer Res Treat. 2013;45(4):313-324. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.313

Abstract PDF PubReader ePub

PURPOSE
Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population.
MATERIALS AND METHODS
We genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer.
RESULTS
TLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers.
CONCLUSION
The genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.

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Association between Toll-like receptor 2 rs4696483 and rs1898830 polymorphisms and the risk of triple-negative breast cancer
Rabeb M. Ghali, Sonia Zaied, Amira Daldoul, Perizat Kanabekova, Wassim Y. Almawi
Gene.2024; 928: 148773. CrossRef
Pathomorphological Manifestations and the Course of the Cervical Cancer Disease Determined by Variations in the TLR4 Gene
Eglė Žilienė, Arturas Inčiūra, Rasa Ugenskienė, Elona Juozaitytė
Diagnostics.2023; 13(12): 1999. CrossRef
Ranking and Prioritizing Risk Factors for Gastric Cancer
Ali Reza Yusefi, Shima Bordbar, Gholamhossein Mehralian, Kamran Bagheri Lankarani, Mohammad Khammarnia, Zahra Kavosi, Peivand Bastani
The Open Public Health Journal.2023;[Epub] CrossRef
Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis
Ayoub Al Othaim, Sulieman Ibraheem Shelash Al-Hawary, Hashem O. Alsaab, Sami G. Almalki, Mazin A. A. Najm, Ahmed Hjazi, Ali Alsalamy, Abbas Firras Almulla, Hamzeh Alizadeh
Frontiers in Genetics.2023;[Epub] CrossRef
Association between EPHA5 methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer
Xu Han, Tianyu Liu, Jiabao Zhai, Chang Liu, Wanyu Wang, Chuang Nie, Qi Wang, Xiaojie Zhu, Haibo Zhou, Wenjing Tian
PeerJ.2022; 10: e13774. CrossRef
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Debashis Dutta, Moumita Majumder, Ramesh Kumar Paidi, Kalipada Pahan
Neurobiology of Disease.2021; 153: 105318. CrossRef
Demethylation of the RB1 promoter concomitant with reactivation of TET2 and TET3 impairs gastric carcinogenesis in K19-Wnt1/C2mE transgenic mice
Donghui Cao, Zhifang Jia, Yanhua Wu, Tongrong Su, Dan Zhao, Menghui Wu, Tetsuya Tsukamoto, Masanobu Oshima, Jing Jiang, Xueyuan Cao
Life Sciences.2020; 263: 118580. CrossRef
Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR) and Inflammation: Focus on the Gastrointestinal (GI) Tract
Evagelia Spanou, Polyxeni Kalisperati, Ioannis S. Pateras, Alexandros Papalampros, Alexandra Barbouti, Athanasios G. Tzioufas, Athanassios Kotsinas, Stavros Sougioultzis
Frontiers in Genetics.2017;[Epub] CrossRef
Increased deaths from gastric cancer in communities living close to waste landfills
Agostino Di Ciaula
International Journal of Environmental Health Research.2016; 26(3): 281. CrossRef
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Zheng-Hua Wang, Zhi-Tu Zhu, Xu-Yang Xiao, Jin Sun
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Natalia CastaÃ±o-RodrÃguez, Nadeem O. Kaakoush, Hazel M. Mitchell
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Prognostic Impact of Polymorphisms in the CASPASE Genes on Survival of Patients with Colorectal Cancer: Jun Young Choi, Jong Gwang Kim, You Jin Lee, Yee Soo Chae, Sang Kyun Sohn, Joon Ho Moon, Byung Woog Kang, Min Kyu Jung, Seong Woo Jeon, Jun Seok Park, Gyu Seog Choi; Cancer Res Treat. 2012;44(1):32-36. Published online March 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.1.32

Abstract PDF PubReader ePub

PURPOSE
This study analyzed potentially functional polymorphisms in CASPASE (CASP) genes and their impact on the prognosis for Korean colorectal cancer patients.
MATERIALS AND METHODS
A total of 397 consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in this study. Genomic DNA from these patients was extracted from fresh colorectal tissue, and the 10 polymorphisms in the CASP3, CASP6, CASP7, CASP8, CASP9, and CASP10 genes were determined using a reverse transcription polymerase chain reaction genotyping assay.
RESULTS
The median patient age was 63 years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had rectal cancer. Univariate and multivariate survival analysis including pathologic stage, patient age, differentiation, and carcinoembryonic antigen level demonstrated that these polymorphisms were not associated with either disease-free or overall survival.
CONCLUSION
None of the 10 polymorphisms in the CASP genes investigated in this study was found to be an independent prognostic marker for Korean patients with curatively resected colorectal cancer.

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Immune-related gene-based model predicts the survival of colorectal carcinoma and reflected various biological statuses
Zhengchun Kang, Bingchen Chen, Xiuzhu Ma, Feihu Yan, Zhen Wang
Frontiers in Molecular Biosciences.2023;[Epub] CrossRef
TCGA dataset screening for genes implicated in endometrial cancer using RNA-seq profiling
Xiaoli Fu, Shuai Cheng, Wei Wang, Oumin Shi, Fuxiao Gao, Yong Li, Qi Wang
Cancer Genetics.2021; 254-255: 40. CrossRef
Mutational analysis of apoptotic genes in familial aggregation of hematological malignancies
Walid Sabri Hamadou, Rahma Mani, Nouha Bouali, Sawsen Besbes, Violaine Bourdon, Rym El Abed, Yosra Ben Youssef, Véronique Mari, Paul Gesta, Hélène Dreyfus, Valérie Bonadona, Catherine Dugast, Hélène Zattara, Laurence Faivre, Tetsuro Noguchi, Abderrahim Kh
Bulletin du Cancer.2021; 108(9): 798. CrossRef
Construction and Characterization of a Synergistic lncRNA–miRNA Network Reveals a Crucial and Prognostic Role of lncRNAs in Colon Cancer
Bin Zhao, Xiusheng Qu, Xin Lv, Qingdong Wang, Deqiang Bian, Fan Yang, Xingwang Zhao, Zhiwu Ji, Jian Ni, Yan Fu, Guorong Xin, Haitao Yu
Frontiers in Genetics.2020;[Epub] CrossRef
CASP8 (rs3834129) and CASP3 (rs4647601) polymorphisms in oropharynx cancer risk, tumor cell differentiation, and prognosis in a cohort of the Brazilian population
Gabriela Arielo Tortorelli, Caroline Torricelli, Juliana Carron, Ericka Francislaine Dias Costa, Leisa Lopes-Aguiar, Bruna Fernandes Carvalho, José Augusto Rinck-Junior, Fernanda Viviane Mariano, Albina Messias Almeida Milani Altemani, Carmen Silvia Passo
Molecular Biology Reports.2019; 46(6): 6557. CrossRef
Screening for implicated genes in colorectal cancer using whole‑genome gene expression profiling
Long‑Ci Sun, Hai‑Xin Qian
Molecular Medicine Reports.2018;[Epub] CrossRef
Apoptosis-inducing and antiproliferative effect by inhibition of miR-182-5p through the regulation of CASP9 expression in human breast cancer
M Sharifi, A Moridnia
Cancer Gene Therapy.2017; 24(2): 75. CrossRef
Inducing cell proliferative prevention in human acute promyelocytic leukemia by miR-182 inhibition through modulation of CASP9 expression
Mahdi Fasihi-Ramandi, Abbas Moridnia, Ali Najafi, Mohammadreza Sharifi
Biomedicine & Pharmacotherapy.2017; 89: 1152. CrossRef
Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population
Fei Liu, Fuqiang Li, Limei Luo, Hanteng Yang, Yonggang Wei, Wentao Wang, Lvnan Yan, Tianfu Wen, Jiayin Yang, Bo Li
Apoptosis.2017; 22(8): 1035. CrossRef
Associations of genetic variation in CASP3 gene with noise-induced hearing loss in a Chinese population: a case–control study
Yinyin Wu, Juntao Ni, Mingjian Qi, Chengjian Cao, Yuxian Shao, Liangwen Xu, Haiyan Ma, Lei Yang
Environmental Health.2017;[Epub] CrossRef
CASP8-652 6N insertion/deletion polymorphism and overall cancer risk: evidence from 49 studies
Jiarong Cai, Qingjian Ye, Suling Luo, Ze Zhuang, Kui He, Zhen-Jian Zhuo, Xiaochun Wan, Juan Cheng
Oncotarget.2017; 8(34): 56780. CrossRef
Association between main Caspase Gene Polymorphisms and the Susceptibility and Prognosis of Colorectal Cancer
Zhiwei Wu, Ye Li, Shuying Li, Lin Zhu, Guangxiao Li, Zhifu Yu, Xiaojuan Zhao, Jie Ge, Binbin Cui, Xinshu Dong, Suli Tian, Fulan Hu, Yashuang Zhao
Medical Oncology.2013;[Epub] CrossRef

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No Association of Insulin-like Growth Factor Gene Polymorphisms with Survival in Patients with Colorectal Cancer: Yoon Young Cho, Jong Gwang Kim, Yee Soo Chae, Sang Kyun Sohn, Byung Woog Kang, Joon Ho Moon, Seong Woo Jeon, Jun Seok Park, Jin Young Park, Gyu Seog Choi; Cancer Res Treat. 2011;43(3):189-194. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.189

Abstract PDF PubReader ePub

PURPOSE
Insulin-like growth factors (IGF) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with colorectal cancer.
MATERIALS AND METHODS
Four hundred and two consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tissue and 8 polymorphisms of IGF genes determined using a real-time polymerase chain reaction genotyping assay.
RESULTS
Pathologic stages after surgery were as follows: stage 0/I (n=85, 21.1%), stage II (n=147, 36.6%), stage III (n=145, 36.1%), and stage IV (n=25, 6.2%). Multivariate survival analysis including stage, age, site of disease, and carcinoembryonic antigen level showed that the progression-free survival for patients with the IGF2 +1280 GG genotype was slightly better than for the patients with the combined IGF2 +1280 AA and AG genotype (p=0.056), although there was no significant difference in the overall survival. However, the other polymorphisms were not associated with survival.
CONCLUSION
None of the 8 IGF1 or IGF2 gene polymorphisms investigated in this study were found to be independent prognostic markers for Korean patients with surgically resected colorectal cancer.

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A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility
Makan Cheraghpour, Masomeh Askari, Sascha Tierling, Sajad Shojaee, Amir Sadeghi, Pardis Ketabi Moghadam, Maryam Khazdouz, Hamid Asadzadeh Aghdaei, Moein Piroozkhah, Ehsan Nazemalhosseini-Mojarad, Nayeralsadat Fatemi
Frontiers in Oncology.2023;[Epub] CrossRef
Association of metabolic syndromes and risk factors with ampullary tumors development: A case-control study in China
Xiao-Dong He, Qiao Wu, Wei Liu, Tao Hong, Jing-Jing Li, Ruo-Yu Miao, Hai-Tao Zhao
World Journal of Gastroenterology.2014; 20(28): 9541. CrossRef
Clinical significance of insulin-like growth factor gene polymorphisms with survival in patients with gastrointestinal stromal tumors
Ohkyoung Kwon, Ho Young Chung, Wansik Yu, Han Ik Bae, Yee Soo Chae, Jong Gwang Kim, Byung Woog Kang, Won Ki Lee
Journal of the Korean Surgical Society.2012; 82(5): 288. CrossRef

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An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population: Wonbeak Yoo, Hae-Yun Jung, Seungjoon Lim, Jae Sook Sung, Kyong Hwa Park, Jeong Seon Ryu, Sang Won Shin, Jun Suk Kim, Jae Hong Seo, Yeul Hong Kim; Cancer Res Treat. 2011;43(2):108-116. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.108

Abstract PDF PubReader ePub

PURPOSE
The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population.
MATERIALS AND METHODS
A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk.
RESULTS
Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer.
CONCLUSION
JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.

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Association Analysis of Polymorphic Gene Variants in the JAK/STAT Signaling Pathway with Aging and Longevity
V. V. Erdman, T. R. Nasibullin, I. A. Tuktarova, R. Sh. Somova, O. E. Mustafina
Russian Journal of Genetics.2019; 55(6): 728. CrossRef

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Influence of Reduced Folate Carrier and Dihydrofolate Reductase Genes on Methotrexate-Induced Cytotoxicity: Seong-Ae Yoon, Jung Ran Choi, Jeong-Oh Kim, Jung-Young Shin, XiangHua Zhang, Jin-Hyoung Kang; Cancer Res Treat. 2010;42(3):163-171. Published online September 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.3.163

Abstract PDF PubReader ePub

Purpose

The aim of this study is to investigate the effect of genetic variations and the expression of the reduced folate carrier (RFC) and dihydrofolate reductase (DHFR) on the drug sensitivity to methotrexate (MTX) in different cancer cell lines.

Materials and Methods

We examined the six human cancer cell lines (MCF-7, AGS, A549, NCI-H23, HCT-116 and Saos-2). The cytotoxicity of MTX was measured by sulforhodamine B (SRB) assay. The expressions of the DHFR and RFC were evaluated by real-time PCR and western blotting. Four single nucleotide polymorphisms (SNPs) of the DHFR and two SNPs of the RFC were genotyped.

Results

The IC₅₀s of MTX was in an extensively broad range from 6.05±0.81 nM to>1,000 nM in the cell lines. The Saos-2 (>1,000 nM) and MCF-7 (114.31±5.34 nM) cells were most resistant to MTX; in contrast, the AGS and HCT-116 cells were highly sensitive to MTX with an IC₅₀ of 6.05±0.81 nM and 13.56±3.76 nM, respectively. A reciprocal change of the RFC and DHFR mRNA expression was found between the MTX-sensitive AGS and MTX-resistant Saos-2 cells. There was no significant difference in the expression levels of RFC protein in both the AGS and Saos-2 cells, whereas DHFR protein was more increased in the MTX-resistant Saos-2 cells treated with MTX. The genotype of the MTX-sensitive AGS cells were mutant variants of the DHFR; in contrast, the Saos-2 cells had the wild-type of the DHFR.

Conclusion

In conclusion, this study showed that inverse change of the RFC and DHFR mRNA and protein expression was associated with RFC and DHFR polymorphisms and it is postulated that this phenomenon might play an important role in sensitivity of certain cancers to MTX.

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Sunil Pandey, Ganga Raju Gedda, Mukeshchand Thakur, Mukesh Lavkush Bhaisare, Abou Talib, M. Shahnawaz Khan, Shou-Mei Wu, Hui-Fen Wu
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Masataka Nakano, Tatsuki Fukami, Saki Gotoh, Miki Nakajima
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Mustafa Saygin, Onder Ozturk, Ozlem Ozmen, Ilter Ilhan, Taner Gonca, Nurhan Gumral, Hikmet Orhan, Rahime Aslankoc
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Boronate Cross‐linked ATP‐ and pH‐Responsive Nanogels for Intracellular Delivery of Anticancer Drugs
Xuejiao Zhang, Katharina Achazi, Rainer Haag
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Construction of pH-sensitive lysozyme/pectin nanogel for tumor methotrexate delivery
Liufeng Lin, Wei Xu, Hongshan Liang, Lei He, Shilin Liu, Yan Li, Bin Li, Yijie Chen
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Dipti Kakkar, Shweta Dumoga, Rohit Kumar, Krishna Chuttani, Anil Kumar Mishra
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DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines
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Spontaneously-forming spheroids as anin vitrocancer cell model for anticancer drug screening
Maria A. Theodoraki, Celso O. Rezende, Oraphin Chantarasriwong, Adriana D. Corben, Emmanuel A. Theodorakis, Mary L. Alpaugh
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Injectable poly(organophosphazene) hydrogel system for effective paclitaxel and doxorubicin combination therapy
Jung-Kyo Cho, Hyo-Jeong Kuh, Soo-Chang Song
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Adipose-derived stem cells retain their regenerative potential after methotrexate treatment
Olivia S. Beane, Vera C. Fonseca, Eric M. Darling
Experimental Cell Research.2014; 327(2): 222. CrossRef
Methotrexate-Loaded PEGylated Chitosan Nanoparticles: Synthesis, Characterization, and in Vitro and in Vivo Antitumoral Activity
Juan Chen, Liuqing Huang, Huixian Lai, Chenghao Lu, Ming Fang, Qiqing Zhang, Xuetao Luo
Molecular Pharmaceutics.2014; 11(7): 2213. CrossRef
pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate
Cheng Gao, Ting Liu, Yinghua Dang, Zhiyan Yu, Wei Wang, Jingjing Guo, Xueqiong Zhang, Guanghua He, Hua Zheng, Yihua Yin, Xiangqi Kong
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Electrochemically controlled release of anticancer drug methotrexate using nanostructured polypyrrole modified with cetylpyridinium: Release kinetics investigation
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Electrochimica Acta.2014; 130: 488. CrossRef
Mg–Al layered double hydroxide–methotrexate nanohybrid drug delivery system: Evaluation of efficacy
Jui Chakraborty, Susanta Roychowdhury, Somoshree Sengupta, Swapankumar Ghosh
Materials Science and Engineering: C.2013; 33(4): 2168. CrossRef
Reduced Folate Carrier and Folylpolyglutamate Synthetase, but not Thymidylate Synthase Predict Survival in Pemetrexed-Treated Patients Suffering from Malignant Pleural Mesothelioma
Fabian Mairinger, Claudia Vollbrecht, Iris Halbwedl, Martina Hatz, Elvira Stacher, Christian Gülly, Franz Quehenberger, Susann Stephan-Falkenau, Jens Kollmeier, Andreas Roth, Thomas Mairinger, Helmut Popper
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In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
Daniele Rubert Nogueira, Lorena Tavano, Montserrat Mitjans, Lourdes Pérez, M. Rosa Infante, M. Pilar Vinardell
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Jung-Kyo Cho, ChangJu Chun, Hyo-Jeong Kuh, Soo-Chang Song
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Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma
M. Joerger, A. D. R. Huitema, G. Illerhaus, A. J. M. Ferreri
Leukemia & Lymphoma.2012; 53(10): 1867. CrossRef
Selective N-Alkylation of β-Alanine Facilitates the Synthesis of a Poly(amino acid)-Based Theranostic Nanoagent
Santimukul Santra, J. Manuel Perez
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Cell-Specific, Activatable, and Theranostic Prodrug for Dual-Targeted Cancer Imaging and Therapy
Santimukul Santra, Charalambos Kaittanis, Oscar J. Santiesteban, J. Manuel Perez
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The reduced folate carrier-1 (RFC1 696T>C) polymorphism is associated with spontaneously aborted embryos in Koreans
Young Joo Jeon, Yi Seul Choi, HyungChul Rah, Youngsok Choi, Tae Ki Yoon, Dong Hee Choi, Nam Keun Kim
Genes & Genomics.2011; 33(3): 223. CrossRef

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No Association between Promoter Polymorphism of STK11 Gene and Lung Cancer Risk in the Korean Population: Jae Sook Sung, Young Mi Whang, Kyong Hwa Park, Jeong-Seon Ryu, Jong Gwon Choi, Jae Hong Seo, Sang Won Shin, Jun Suk Kim, Yeul Hong Kim; Cancer Res Treat. 2009;41(4):211-217. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.211

Abstract PDF PubReader ePub

Purpose

Serine-threonine kinase11 (STK11) was originally identified in 1997 as the causative mutation that's responsible for Peutz-Jeghers Syndrome (PJS). Several recent studies have reported that the STK11 gene is an important human tumor suppressor gene in lung cancer. We evaluated the associations between the polymorphisms of the STK11 promoter region and the risk of lung cancer in 901 Koreans.

Materials and Methods

By direct sequencing, we first discovered three novel polymorphisms (-1,795 T>C, -981 C>T and -160 G>T) and four known polymorphisms (-1,580 C>T, -1,494 A>C, -881 A>G and -458 G>C) of the STK11 promoter region in 24 blood samples of 24 Korean lung cancer patients. Further genotype analyses were then performed on 443 lung cancer patients and 458 controls.

Results

We discovered three novel polymorphisms and we identified four known polymorphisms of the STK11 promoter region in a Korean population. Statistical analyses revealed that the genotypes and haplotypes in the STK11 gene were not significantly associated with the risk of lung cancer in a Korean population.

Conclusion

This is the first study that's focused on the association of STK11 promoter polymorphisms and the risk of lung cancer in a Korean population. To evaluate the role of the STK11 gene for the risk of lung cancer, the genotypes of the STK11 promoter region (-1,795 T>C, -1,494 A>C and -160 G>T) were determined in 901 Koreans, yet the result revealed no significant difference between the lung cancer patients and the controls. These results suggest that the three promoter polymorphisms we studied are not important risk factors for the susceptibility to lung cancer in Koreans.

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A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility
Se-Lyun Yoon, Yun-Gil Roh, In-Sun Chu, Jeonghoon Heo, Seung Il Kim, Heekyung Chang, Tae-Hong Kang, Jin Woong Chung, Sang Seok Koh, Vladimir Larionov, Sun-Hee Leem
Experimental & Molecular Medicine.2016; 48(7): e246. CrossRef
Integrated Analysis of Transcriptomes of Cancer Cell Lines and Patient Samples Reveals STK11/LKB1–Driven Regulation of cAMP Phosphodiesterase-4D
Ningning He, Nayoung Kim, Mee Song, Choa Park, Somin Kim, Eun Young Park, Hwa Young Yim, Kyunga Kim, Jong Hoon Park, Keun Il Kim, Fan Zhang, Gordon B. Mills, Sukjoon Yoon
Molecular Cancer Therapeutics.2014; 13(10): 2463. CrossRef
Hot embossed polyethylene through-hole chips for bead-based microfluidicdevices
Jie Chou, Nan Du, Tina Ou, Pierre N. Floriano, Nicolaos Christodoulides, John T. McDevitt
Biosensors and Bioelectronics.2013; 42: 653. CrossRef
Discovery and Evaluation of Polymorphisms in theAKT2andAKT3Promoter Regions for Risk of Korean Lung Cancer
Jae Sook Sung, Kyong Hwa Park, Seung Tae Kim, Yeul Hong Kim
Genomics & Informatics.2012; 10(3): 167. CrossRef

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Association of Single Nucleotide Polymorphisms in PIM-1 Gene with the Risk of Korean Lung Cancer: Dae Sik Kim, Jae Sook Sung, Eun Soon Shin, Jeong-Seon Ryu, In Keun Choi, Kyong Hwa Park, Yong Park, Eui Bae Kim, Seh Jong Park, Yeul Hong Kim; Cancer Res Treat. 2008;40(4):190-196. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.190

Abstract PDF PubReader ePub

Purpose

The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population.

Materials and Methods

To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects.

Results

We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007).

Conclusions

The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.

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A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target
Ajaya Kumar Rout, Budheswar Dehury, Satya Narayan Parida, Sushree Swati Rout, Rajkumar Jena, Neha Kaushik, Nagendra Kumar Kaushik, Sukanta Kumar Pradhan, Chita Ranjan Sahoo, Ashok Kumar Singh, Meenakshi Arya, Bijay Kumar Behera
International Journal of Biological Macromolecules.2024; 270: 132030. CrossRef
Impact of Pim1 mutations on the survival outcomes of patients with breast cancer: Insights from a clinical study
Syed Sultan Beevi, Kavitha Anbrasu, Vinod Kumar Verma, Nagesh Kishan Panchal, Krishna Kiran Kannepalli, Raghu Ram Pillarisetti, Sailaja Madigubba, Jyotsana Dwivedi, Neha Damodar, Radhika Chowdary Darapuneni
Human Gene.2024; 40: 201295. CrossRef
HCG11 inhibits salivary adenoid cystic carcinoma by upregulating EphA2 via binding to miR-1297
Shujuan Yan, Meng Wang
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2023; 135(2): 257. CrossRef
Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995. CrossRef
Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC)
Jiajie Xu, Xin Zhu, Qingling Li, Chao Chen, Zhenying Guo, Zhuo Tan, Chuanming Zheng, Minghua Ge
Cancer Cell International.2018;[Epub] CrossRef
PIM Kinase as an Executional Target in Cancer
Xinning Zhang, Mengqiu Song, Joydeb Kumar Kundu, Mee-Hyun Lee, Zhen-Zhen Liu
Journal of Cancer Prevention.2018; 23(3): 109. CrossRef
HistoneH3 demethylase JMJD2A promotes growth of liver cancer cells through up-regulating miR372
Jiahui An, Jie Xu, Jiao Li, Song Jia, Xiaonan Li, Yanan Lu, Yuxin Yang, Zhuojia Lin, Xiaoru Xin, Mengying Wu, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Dongdong Lu
Oncotarget.2017; 8(30): 49093. CrossRef
Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC)
Yi Jin, Da-yue Tong, Lu-ying Tang, Jian-ning Chen, Jing Zhou, Zhi-ying Feng, Chun-kui Shao
Chinese Journal of Cancer Research.2012; 24(2): 103. CrossRef
Overexpression of Osteopontin, αvβ3 and Pim-1 Associated with Prognostically Important Clinicopathologic Variables in Non-Small Cell Lung Cancer
Yi Jin, Da-yue Tong, Jian-ning Chen, Zhi-ying Feng, Jian-yong Yang, Chun-kui Shao, Jia-ping Li, Rossella Rota
PLoS ONE.2012; 7(10): e48575. CrossRef
No Association between PIK3CA Polymorphism and Lung Cancer Risk in the Korean Population
Jae-Sook Sung, Kyong-Hwa Park, Seung-Tae Kim, Jae-Hong Seo, Sang-Won Shin, Jun-Suk Kim, Yeul-Hong Kim
Genomics & Informatics.2010; 8(4): 194. CrossRef

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Genetic Polymorphism of Epoxide Hydrolase and GSTM1 in Lung Cancer Susceptibility of Korean Population: Jun Hwa Hwang, Kyu Sik Kim, Yu Il Kim, Eun Joung Kim, Kyung Hwa Park, Gye Jung Cho, Jin Young Ju, Sung Chul Lim, Young Chul Kim, Kyung Ok Park, Jong Tae Park, Sung Ja Ahn; Cancer Res Treat. 2003;35(6):483-488. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.483

Abstract PDF: PURPOSE
Although 80~90% of patients with lung cancer are smokers, only 11% of smokers develop lung cancer. Genetic susceptibility according to the polymorphism of the epoxide hydrolase (mEPHX) gene and homozygous deletion of GSTM1 (M1 subunit of Glutathione S transferase) was studied in this case control study. MATERIALS AND METHODS: Genomic DNA from 76 subjects with lung cancer (40 squamous cell carcinoma, 13 adenocarcinoma, 10 subtype undetermined non-small cell lung cancer, and 13 small cell lung carcinoma) and 62 age- matched controls were extracted from peripheral white blood cells. PCR and RFLP (restriction fragments length polymorphism) with restriction enzyme (RsaI) and automatic sequencing were used for mEPHX genotyping (T-->C, Tyr113His) in exon 3 and (A-->G, His139Arg) in exon 4. Looking for homozygous deletions of GSTM1, multiplex PCR with primers for the GSTM1 gene and coagulation factor V gene (as positive control) were performed. RESULTS: The age distribution between the cancer and control groups were similar (63.6 7.2 vs. 61.1 7.9 years). The lung cancer group, however, had more smokers (73.3%, 44/60) than the control group (21/54, 38.9%, p<0.001). The rate of homozygous deletion of the GSTM1 gene was significantly higher in the lung cancer group (65.8%, 50/76) than in the control group (46.8%, 29/62, p<0.05), causing the relative risk of GSTM1 deletion for lung cancer as 2.19 (95% CI: 1.10~4.35, p=0.02). Among 118 subjects whose mEPHX gene polymorphisms were studied, 62 (52.5%) subjects showed genotypes with slow enzyme activity while 45 (38.1%) showed normal enzyme activity and 11 (9.3%) showed fast enzyme activity. There was no significant difference in the distribution of mEPHX gene polymorphisms between the two groups. CONCLUSION: The homozygous deletion of the GSTM1 gene was associated with high lung cancer susceptibility, whereas the mEPHX genotype showed no significant connection with risk of lung cancer in a sample Korean population.

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l-myc Polymorphism in Gastric Cancer, Lung Cancer, and Hepatocellular Carcinoma: Min Su Park, Sae Bin Jung, Yeon Hee Park, Bong Seog Kim, Hyun Ju Park, Hee Jae Lee, Soon Ae Kim, Bong Keun Choe, Joo Ho Chung; Cancer Res Treat. 2002;34(6):436-438. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.436

Abstract PDF

PURPOSE
This study was performed to see if a particular polymorphism in the l-myc, a nuclear oncogene at the 1p32 locus, might be associated with greater risk of gastric cancer, lung cancer and hepatocellular carcinomas (HCC) in Korean patients.
MATERIALS AND METHODS
Genomic DNA, derived from patients diagnosed with gastric cancer (n=57), lung cancer (n=39), HCC (n=35) and healthy individuals (n= 176), was examined. The l-myc polymorphism under study was visualized by PCR followed by EcoRI digestion.
RESULTS
There was no significant difference in the distribution of the l-myc polymorphism genotypes and allele frequencies between the cancer patients and the controls.
CONCLUSION
The l-myc polymorphism does not appear to be indicative of elevated risk of cancers of the stomach, lung and HCC.

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An E2F5-TFDP1-BRG1 Complex Mediates Transcriptional Activation of MYCN in Hepatocytes
Zhiwen Fan, Ming Kong, Xiulian Miao, Yan Guo, Haozhen Ren, Jinglin Wang, Shuai Wang, Ning Tang, Longcheng Shang, Zhengyi Zhu, Hanyi Liu, Wei Zhu, Xiaolei Shi
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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No Association between Catalase Gene Polymorphism and Gastric Carcinoma and Hepatocellular Carcinoma in Koreans: Ji Hyun Lee, Ran Young Park, Chang Soo Lee, Euh Jun Jeoung, Su Youn Nam, Jae Gun Lee, Kye Young Han, Hee Jae Lee, Joo Ho Chung, Yun Gul Ahn, Sung Vin Yim, Jae Young Cho, Yeon Hee Park; Cancer Res Treat. 2002;34(6):432-435. Published online December 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.6.432

Abstract PDF

PURPOSE
Oxidative stress has been implicated in the pathogenesis of various diseases. Catalase is one of the main defense mechanisms against oxidative stress. To examine the possible relationship between oxidative stress, and gastric and hepatocellular carcinomas, HinfI restriction length polymorphism (RFLP) in the human catalase gene was assessed.
MATERIALS AND METHODS
The genotype and allele frequencies in the promoter region of the catalase gene were studied by PCR-RFLP in 108 Korean controls, 80 Korean gastric carcinoma (GC) and 106 Korean hepatocellular carcinoma (HCC) patients.
RESULTS
No statistically significant differences were found in the genotypic distribution and allelic frequencies between the controls and both types of carcinoma patient.
CONCLUSION
To address the possible contribution of oxidative stresses to the pathogenesis of gastric and hepatocellular carcinomas, the associations between the catalase gene polymorphism and GC and HCC susceptibilities were studied. As a result, the catalase gene polymorphism was found not to be determinant of GC and HCC susceptibilities. Further studies are required on various other oxidative stress related genes to elucidate the mechanisms of GC and HCC.

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Organelle stress and alterations in interorganelle crosstalk during liver fibrosis
Saloni Sinha, Nora Hassan, Robert E. Schwartz
Hepatology.2024; 79(2): 482. CrossRef
Two common functional catalase gene polymorphisms (rs1001179 and rs794316) and cancer susceptibility: evidence from 14,942 cancer cases and 43,285 controls
Kang Liu, Xinghan Liu, Meng Wang, Xijing Wang, Huafeng Kang, Shuai Lin, Pengtao Yang, Cong Dai, Peng Xu, Shanli Li, Zhijun Dai
Oncotarget.2016; 7(39): 62954. CrossRef
Association Between Catalase Gene Polymorphisms and Risk of Chronic Hepatitis B, Hepatitis B Virus-Related Liver Cirrhosis and Hepatocellular Carcinoma in Guangxi Population
Yanqiong Liu, Li Xie, Jiangyang Zhao, Xiuli Huang, Liuying Song, Jingrong Luo, Liping Ma, Shan Li, Xue Qin
Medicine.2015; 94(13): e702. CrossRef

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Polymorphisms of p53, p21 and IRF-1 and Cervical Cancer Susceptibility in Korean Women: Sung Jong Lee, Sung Eun Namkoong, Won Chul Lee, Jae Woong Sul, Sun Ha Jee, Youn Kyoung You, Jong Eun Lee, Jong Sup Park; Cancer Res Treat. 2002;34(5):357-364. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.357

Abstract PDF

PURPOSE
The aim of this study was to identify gene- gene and gene-environmental factor on cervical carcinogenesis in Korean women.
MATERIALS AND METHODS
We evaluated 185 women patients who had cervical cancer with 345 normal control healthy women. The single nucleotide polymorphisms (SNPs) of the p53 codon 72, the p21 codon 31 and the IRF-1 intron 6 were evaluated from extracted DNA of peripheral blood with an automatic DNA sequencer. The difference of each SNP, gene-gene and gene-environmental interaction between normal controls and patients, were evaluated in an adjusted environmental background.
RESULTS
With regard to environmental factors, the cervical cancer increased in the women with a lower level of education, a younger age at first sexual intercourse and with the increased number of children borne. The women who had p53 (Arg/Arg), IRF-1 (T/T) and an education of less than 6 years showed a 14.7 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and an education of more than 15 years. The women who had p53 (Arg/Arg), p21 (Ser/Ser) and more than 3 children showed a 6.4 fold increased risk of cervical cancer than those women who had p53 (~Pro), p21 (~Arg) and had borne no child. The women who had p53 (Arg/Arg), IRF-1 (T/T) and had experience of first sexual intercourse before the age of 22-years showed a 5.5 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and had experience of first sexual intercourse after the age of 26-years.
CONCLUSION
We found that the level of education, the age at first intercourse, and the number of children borne, were independent risk factors in cervical carcinogenesis. The specific combination of p53, p21 and IRF-1 gene-gene and gene-environmental interactions were significantly noted in the cervical carcinogenesis of Korean women.

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Distinctive cell cycle regulatory protein profiles by adenovirus delivery of p53 in human papillomavirus-associated cancer cells
H.-S. JIN, S.-M. BAE, Y.-W. KIM, J.-M. LEE, S.-E. NAMKOONG, B.-D. HAN, Y.-J. LEE, C.-K. KIM, H.-J. CHUN, W.-S. AHN
International Journal of Gynecological Cancer.2006; 16(2): 698. CrossRef
Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells
Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn
Cancer Research and Treatment.2006; 38(3): 168. CrossRef
Cellular process classification of human papillomavirus-16-positive SiHa cervical carcinoma cell using Gene Ontology
W. S. Ahn, M.-J. Seo, S. M. Bae, J. M. Lee, S. E. Namkoong, C. K. Kim, Y.-W. Kim
International Journal of Gynecological Cancer.2005; 15(1): 94. CrossRef

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Glutathione S-transferase P1 Genetic Polymorphisms and Breast Cancer Risk: Sook Un Kim, Kyoung Mu Lee, Sue Kyung Park, Keun Young Yoo, Dong Young Noh, Kook Jin Choe, Se Hyun Ahn, Daehee Kang; Cancer Res Treat. 2002;34(3):205-211. Published online June 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.3.205

Abstract PDF

PURPOSE
To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted in South Korea. MATERIALS AND METGODS: The study population consisted of 171 histologically confirmed incidents of breast cancer cases, and 171 age-matched controls with no present, or previous, history of cancer. A PCR method was used for the genotyping analyses, and statistical evaluation was performed by an unconditional logistic regression model.
RESULTS
No association was observed in the study subjects, or the premenopausal women group with GSTP1 Val allele. However, postmenopausal women with GSTP1 Val allele had a reduced risk of breast cancer (OR=0.3, 95% CI=0.1~0.7). When the data were stratified, by the known risk factors of breast cancer, a significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); women with GSTP1 Val allele, that drank regularly, had a 3.0-fold increased risk of breast cancer (95% CI=1.1~7.9), whereas women with GSTP1 Val allele, that never drink, had protective effects (OR=0.4, 95% CI=0.2~0.8).
CONCLUSION
Our findings suggest that GSTP1 Ile105Val polymorphism influences the individual susceptibility to breast cancer, and that this effect may be modified by alcohol consumption.

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Attributable fraction of alcohol consumption on cancer using population-based nationwide cancer incidence and mortality data in the Republic of Korea
Sohee Park, Hai-Rim Shin, Boram Lee, Aesun Shin, Kyu-Won Jung, Duk-Hee Lee, Sun Ha Jee, Sung-Il Cho, Sue Kyung Park, Mathieu Boniol, Paolo Boffetta, Elisabete Weiderpass
BMC Cancer.2014;[Epub] CrossRef

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p53 Codon 72 Polymorphism and Cervical Adenocarcinoma Risk in Korean Women: Jeong Hwa Kim, Ju Won Roh, Kyung Sun Kim, Hyeon Jung Jung, Jae Weon Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; Cancer Res Treat. 2001;33(3):243-249. Published online June 30, 2001; DOI: https://doi.org/10.4143/crt.2001.33.3.243

Abstract PDF: PURPOSE
This study was undertaken to analyze whether the p53 codon 72 single nucleotide polymorphism might be correlated with the risk and/or the prognosis of cervical cancer in Korean women.
MATERIALS AND METHODS
Peripheral blood samples derived from patients with cervical squamous cell carcinoma (SCC) (n=68), cervical adenocarcinoma (n=37), cervical intraepithelial neoplasia (CIN) III (n=98) and normal controls (n=98) were examined. Germline genomic DNA was extracted from peripheral blood leukocytes and examined by PCR amplification of the specific alleles assay described by Storey et al.5 Statistical analysis was performed using the Chi-Square test or the Kaplan-Meier survival analysis, logistic regression analysis.
RESULTS
The proportions of individuals who were homozygous for the proline allele, and heterozygous for the two allele, homozygous for arginine allele in each group were 15%, 47%, 38% in the SCC group; 6%, 7%, 24% in the adenocarcinoma group; 7%, 33%, 60% in the CIN III group; and 11%, 38%, 51% in the control group. No significant difference was found between the three groups (p>0.05). However there was a significant difference in the adenocarcinoma group (p<0.05). Arg/Arg homozygote reduced the risk of adenocarcinoma. No significant difference existed in 5-year survival rates in the three groups (p=0.22 in SCC, p=0.91 in adenocarcinoma).
CONCLUSION
These findings suggest that Arg/Arg homozygocity of the p53 codon 72 would be a protective factor against the development of cervical adenocarcinoma.

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p21WAF1/CIP1 Codon 31 Polymorphism in Korean Women: Association with Cervical Cancer Susceptibility and Prognosis: Ju Won Roh, Kyung Sun Kim, Jae Weon Kim, Moon Hong Kim, Hyun Hoon Chung, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 2000;32(6):1050-1058.

Abstract PDF: PURPOSE
The aim of this study was to determine whether certain genotype of p21WAF1/Cip1 might be associated with risk of cervical cancer in Korean women.
MATERIALS AND METHODS
We used the specimens derived from cervical cancer (n=111) composed of two histologic groups; SCCA (n=67) and adenocarcinoma (n=44), CIN III (n=101) and controls (n=98). For the determination of p21WAF1/Cip1 polymorphism, DNA was examined by PCR-RFLP using BsmAI. We compared the distribution of p21WAF1/Cip1 genotype of Korean women with that of other ethnic groups and analyzed the distribution of invasive cancer, CIN III and controls.
RESULTS
The genotype frequency of controls was different from that of Caucasian and Chinese (p<0.001) but similar to that of Japanese (p=0.21). There was no difference in the genotype frequency of p21WAF1/Cip1 among SCCA, CIN III and controls (p>0.05). A significant increase of Ser/Ser genotype was found in adenocarcinoma patients with high-risk HPV compared with the controls (p=0.009). The OR was 3.59, 95% CI=1.55~8.31, when comparing that group with controls. However, we could not find differences of prognosis.
CONCLUSION
We found that codon 31 Ser/Ser homozygote of the p21WAF1/Cip1 would be a risk factor for the adenocarcinoma of cervix associated with high-risk HPV in Korean women.

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Polymorphisms in E6 Gene of Human Papillomavirus Type 16 Found in Cervical Tissues from Korean Women: Jae Weon Kim, Ju Won Roh, Moon Hong Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 2000;32(5):875-883.

Abstract PDF: PURPOSE
To examine the distribution of HPV 16 E6 polymorphisms and analyse the possible association between the polymorphisms and cervical cancer development in Korean women.
MATERIALS AND METHODS
Fifty-four cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the E6 gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy ter mination method and the results obtained from sequencing were analysed. And newly designed PASA method was tried to develop rapid test for identification of the most commonly detected variation.
RESULTS
Among the 27 cervical cancer cases, only two (7.4%) was found as a prototype. Among 11 kind of variants identified in total, 4 variants (5 nucleotide sites) which were never reported before has been found, registered firstly to GenBank. The most frequently found variation was D25E, absolutely different from the previous reports from the western country. There was no statistically significant trend for the D25E variation to be more frequently detected in cancerous lesions than in noncancerous lesions. All of the DNA sequencing results observed could be confirmed by PASA method.
CONCLUSION
These results suggest that Korean-specific genetic factors might operate during the cervical carcinogenesis.

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Correlation between Genetic Polymorphism of CYP2D6 and CYP1A1 and Susceptibility of Renal Cell Carcinoma in Korean: Kyu Wook Park, Se Il Jung, Gyung Woo Jung, Heon Young Kwon, Jin Sook Jeong, Jin Ho Chun, Jin Han Yoon; J Korean Cancer Assoc. 2000;32(4):801-809.

Abstract PDF: PURPOSE
Many of the enzymes handling environmental factors are polymorphic and may confer variable susceptibility to renal cell carcinoma (RCC). Among those, the author studied genetic polymorphisms of CYP2D6 (B & T) and CYP1A1 in RCCs and controls in Korean.
MATERIALS AND METHODS
Using 132 RCCs and 94 controls, first PCR products were obtained in 104 RCCs and 94 controls with CYP2D6, and 74 RCCs and 56 controls with CYP1A1. Res triction enzyme - BstN I/EcoN I for CYP2D6 (B & T), and NCo I for CYP1A1-digestion was followed to analyze constitutive DNA.
RESULTS
In both RCCs and controls, no mutant allele of CYP2D6 (B & T) was detected and the susceptibility for occurrence of RCC was unable to evaluate. With CYP1A1 RFLP, homozy gous wild type (WW) was seen in 68 (52.3%; 37 RCCs, 31 controls), heterozygous mutant type (WM) in 54 (41.5%; 32 RCCs, 22 controls) and homozygous mutant type (MM) in 8 (6.2%; 5 RCCs, 3 controls). The odds ratios (95% CI) of RCC susceptibility for CYP1A1 genotype were 1.15 for WM and 1.36 for MM. Even though not significant statistically, higher tendency in MM presented.
CONCLUSION
There is no association between susceptibility for the occurrence of RCC and genetic polymorphism of CYP2D6 (B & T) and CYP1A1.

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Somatic Mutations of APC Presenting Polymorphisms in the Hamartomatous Polyps of the Colon: Jin Cheon Kim, Seon Ae Roh, Hee Cheol Kim, Chang Sik Yu, Nichoias E Beck, Walter F Bodmer; J Korean Cancer Assoc. 1999;31(6):1288-1296.

Abstract PDF: No abstract available.

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A Case-Control Study of the Association between Glutathione S-transferase (GST) M1 and T1 Genetic Polymorphism and Breast Cancer in Korean Women: Preliminary report: Sue Kyung Park, Dae Hee Kang, Byung Joo Park, Seung Joon Lee, Young Chul Kim, Han Sung Kang, Jun Suk Suh, Se Hyun Ahn, Dong Young Noh, Kuk Jin Choe; J Korean Cancer Assoc. 1999;31(4):653-662.

Abstract PDF: PURPOSE
A hospital-based case-control study was conducted to evaluate the role of glutathione-S-transferase (GST) Ml and Tl genetic polymorphism for developing breast cancer in Korea.
MATERIALS AND METHODS
Histologically confirmed incident cases of breast cancer (n=176) were selected from inpatients at the Department of General Surgery, Seoul National University Hospital (SNUH), Borame hospital, and Asan Medical Center from 1994 to 1998. Women with no self-reporting past history of any malignancies who were selected from the inpatients at the same department at three hospitals during the same period served as controls (n 118). Information on the life-styles including reproductive factors were obtained by interview using questionnaire. Age and education adjusted odds ratio and 95% confidence interval were estimated by unconditional linear logistic regression.
RESULTS
These subjects had similar risk factors for developing breast cancer to general Korean population based on other epidetniologic studies previously performed in Korea. GSTI1 null type showed a borderline significance relation in the breast cancer risk (adjusted OR=1.6, 95% CI=0.96-2.62), however, GSTM1 null type was not significant (adjusted OR=1.1, 95% CI=0.67-1.80). Particularly noteworthy was an borderline increasing tendency (p<0.1) of the breast cancer risk with the risk null genotypes assessed by multivariate logistic regression model after adjusting age and education: the putative low-risk genotype with both GSTM1 & GSTT1 wild type, OR=1.0; one putative high risk genotype with GSTM1 null or GSTMl null type, OR=1.9 (95% CI=0.92-3.74); all two putative high risk genotype with both GSTM1 & GSTT1 null type, OR=2.0 (95% CI=0.89-4.68).
CONCLUSIONS
These findings suggest that both GSTMl and GSTT1 null type might be the risk factor of developing breast cancer in Korean women. Further investigation with larger sample size should be needed to provide more concrete information on the role of GST genetic polymorphism in breast cancer.

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Association of Genetic Polymorphism of Glutathions S-transferase M1 and T1 and Bladder Cancer: Seung Joon Lee, Dae Hee Kang, Soo Hun Cho, Soo Woong Kim, Moon Soo Park, Han Yong Choi, Whang Choi; J Korean Cancer Assoc. 1999;31(3):548-555.

Abstract PDF: PURPOSE
Smoking and high-risk occupation are known to be the risk factors of bladder cancer. The carcinogen-metabolizing enzymes in human body such as GSTM1 and GSTT1 have also been regarded as risk factors in many cancers because the activities of those enzymes play a role in metabolizing the carcinogen. A case control study was conducted to evaluate the role of known risk factors (smoking and high-risk occupational history) and the genetic polymorphism of GSTM1 and GSIT1 in blader carcinogenesis in Korean men.
MATERIALS AND METHODS
The pathologically proven bladder cancer cases were selected from three hospitals in Seoul (Seoul National University Hospital, Boramae Hospital, and Sam-Sung Medical Center) and the patients older than 40 years of age with the nonmalig nant urinary tract diseases were selected as the controls from the same hospitals. The informations of demographical characteristics, smoking, and occupational history was obtained by the trained interviewer and the genetic polymorphisms of GSTM1 and GSTT1 were assayed by multiplex PCR. The statistical analysis was performed by multiple logistic regression.
RESULTS
Neither smoking nor high-risk occupational history was statistically significant risk factor of the bladder cancer. However, the GSTM1 null-type showed borderline significance (OR 1.49; 95% CI 0.92-2.41) and both GSTM1 and GSlT1 null-type was statistically significant risk factor of bladder cancer when compared with both normal genotype (OR-2.43; 95% CI 1.13-5.24) after age and smoking history were adjusted.
CONCLUSION
The concurrent null-type of GSTM1 and GSTT1 increases the risk of bladder cancer in Korean men.

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The Association of p53 Mutation with Human Papillomavirus Type 16 , 18 Infection and its Clinical Significance: Chang Soo Park, Yong Sang Song, Chang Won Koh, Hye Won Jeon, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1996;28(1):122-138.

Abstract PDF: Recent several studies have suggested that inactivation of p53 gene could occur by two theoretical mechanisms in cervical cancer. The E6 transforming protein of oncogenic human papillomavirus(HPV) binds to and promotes the degradation of p53 protein, or the mutation of the p53 gene could result in its inactivation without HPV infection. The purpose of this study were to investigate HPV infection and p53 mutation according to the status of lymph node metastasis and to analyse the relationship and role of HPV infection and p53 alteration in the advance and metastasis of cervical cancer. Paraffin embedded tissue sections were obtained from 30 patients with cervical cancer, each l5 patients with or without lymph node metastasis. The PCR and Southern blotting were used for the detection of HPV l6/18 DNA. Alteration of p53 activity was evaluated by immunohistochemistry using MAb DO7 and polymerase chain reaction with single stranded conformation polymorphism(PCR-SSCP). There was no significant difference in HPV infection between two groups, 73.3%(l l/15) in negative lymph node group and 80.0%(l2/15) in positive lymph node group. Although by immunohistochemistry p53 alterations were found more frequently in positive lymph node group(46.7%) than in negative lymph node group(20.0%), there was no significant difference between two groups. HPV negative cervical cancers had more p53 alterations(57.l%) than HPV positive cervical cancers(26.1%). However, there was no significant inverse relationship between HPV infection and p53 alteration. In conclusion, these data suggest that HPV infection and p53 alteration may play an important role independantly in the development of cervical cancer and p53 alteration may be associated with the advance and metastasis in some cases.

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CA Repeat Polymorphism at the D5S346 Locus Tightly Linked to Adenomatous Polyposis Coli ( APC ) Gene in Korean Population: Hye Jung Han, Yong Jin Won, Kyu Joo Park, Jae Gahb Park; J Korean Cancer Assoc. 1996;28(3):533-544.

Abstract PDF: A subclass of human tandemly repeated DNA contains very short simple sequence repeats such as (dC-dA). (dG-dT), designated as CA repeats or (CA). It is now recognized that there are 50,000-100,000 interspaced (CA), blocks in the human genome. The function of these repeat sequences remains obscure, but since (CA). exhibit high degree of length polymorphisms and Mendelian inheritance, they can be extremely useful for genetic diagnosis of hereditary diseases. In this paper, we have examined the CA repeat polymorphism at the D5S346 locus, which is located 30~70kb downstream to the APC (adenomatous polyposis coli) gene responsible for development of familial adenomatous polyposis, in 55 unrelated Koreans. We were able to identify 11 different alleles ranging from 114 to 138 base pairs(bp) in size. The observed heterozygosity was 0.60. Using this information, we could successfully make presymptomatic diagnosis of all the at-risk individuals in 2 Korean familial adenomatous polyposis(FAP) families. Our result indicates that higly polymorphic dinucleotide (CA)-repeat marker D5S346 can serve as an important tool for presymptomatic diagnosis of Korean FAP families.

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