Purpose
Obesity has been determined to be associated with fat mass and obesity-associated (FTO) gene and thyroid cancer risk. However, the effect of combined interactions between obesity and the FTO gene on thyroid cancer needs further investigation. This study aimed to examine whether interactions between body mass index (BMI) and the FTO gene are associated with an increased risk of thyroid cancer.
Materials and Methods
A total of 705 thyroid cancer cases and 705 sex- and age-matched normal controls were selected from the Cancer Screenee Cohort in National Cancer Center, Korea. A conditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the measure of associations and the combined effect of BMI and FTO gene on thyroid cancer.
Results
BMI was associated with an increased risk of thyroid cancer in subclasses of overweight (23-24.9 kg/m2; adjusted OR, 1.50; 95% CI, 1.12 to 2.00) and obese (≥ 25 kg/m2) (adjusted OR, 1.62; 95% CI, 1.23 to 2.14). There were positive associations between the FTO genetic variants rs8047395 and rs8044769 and an increased risk of thyroid cancer. Additionally, the combination of BMI subclasses and FTO gene variants was significantly associated with thyroid cancer risk in the codominant (rs17817288), dominant (rs9937053, rs12149832, rs1861867, and rs7195539), and recessive (rs17817288 and rs8044769) models.
Conclusion
Findings from this study identified the effects of BMI on thyroid cancer risk among individuals carrying rs17817288, rs9937053, rs12149832, rs1861867, rs7195539, and rs8044769, whereas the effects of BMI may be modified according to individual characteristics of other FTO variants.
Citations
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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 (pinteraction=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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Purpose
Heterochromatin protein 1γ (HP1γ) interacts with chromosomes by binding to lysine 9-methylated histone H3 or DNA/RNA. HP1γ is involved in various biological processes. The purpose of this study is to gain an understanding of how HP1γ functions in these processes by identifying HP1γ-binding proteins using mass spectrometry.
Materials and Methods
We performed affinity purification of HP1γ-binding proteins using G1/S phase or prometaphase HEK293T cell lysates that transiently express mock or FLAG-HP1γ. Coomassie staining was performed for HP1γ-binding complexes, using cell lysates prepared by affinity chromatography FLAG-agarose beads, and the bands were digested and then analyzed using a mass spectrometry.
Results
We identified 99 HP1γ-binding proteins with diverse cellular functions, including spliceosome, regulation of the actin cytoskeleton, tight junction, pathogenic Escherichia coli infection, mammalian target of rapamycin signaling pathway, nucleotide excision repair, DNA replication, homologous recombination, and mismatch repair.
Conclusion
Our results suggested that HP1γ is functionally active in DNA damage response via proteinprotein interaction.
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PURPOSE Cell-cell interactions determine normal prostate development and subsequent neoplastic transfor mation. The progression of prostate cancer from androgen-dependent to androgen-independent states involves multiple steps of genetic changes mediated by tumor-microenvironment interactions. To understand the epigenetic factors that lead to progression, we studied if 1) androgen-dependent and non-metastatic LNCaP may interact with prostate or bone fibroblasts under microgravity-simulated conditions in vitro. 2) LNCaP may interact with prostate fibroblasts in vivo, and acquire androgen-independence and metastatic potential. MATERIALS AND METHODS The LNCaP sublines were generated as follows. 1) LNCaP cells were grown in vitro either alone or with prostate or bone fibroblasts under microgravity-simulated conditions. 2) LNCaP cells were grown in vivo as chimeric tumors with prostate fibroblasts.
The LNCaP sublines were characterized by studies of chromosomal analysis, comparative genomic hybridization and, in vivo tumorigenicity and metastatic potential. RESULTS In comparison to the parental LNCaP cells, the LNCaP sublines underwent permanent genotypic and phenotypic changes manifested in androgen-independence and metastatic potential. CONCLUSION These results emphasize the importance of cell-cell interaction as a critical determinant that could "induce" or "select" progenies favoring enhanced prostate cancer growth and progression. This concept favors the development of toxic gene therapy targeting both prostate cancer epithelium and supporting bone stroma for an effective eradication and prevention of prostate cancer bone metastasis.
Kyoung Mu Lee, Seung Joon Lee, Sue Kyung Park, Sang Yun Lee, Hyung June Im, Ki Jung Yoon, In Mi Choi, Young Ju Lee, Soo Ung Kim, Hwang Choi, Seung Ho Choi, Young Whan Kim, Soo Han Cho, Daehee Kang
PURPOSE The interactive effects of genetic polymorphisms of cytochrome P4502E1 (CYP2E1) & N-acetyltransferase 1 (NAT1) and smoking on lung cancer development were evaluated in hospital based case-control study. MATERIALS AND METHODS Male lung cancer patients (N= 157) and the male patients with no present or previous history of systemic illnesses who visited the urology department (N=138) were recruited (1998-1999). CYP2E1 & NAT1 genotypes were determined by PCR-RFLP method using RsaI and MboII digestion, respectively. RESULTS CYP2E1 c2 or NAT1 *10 allele did not increased the risk of lung cancer. Heavy smokers (35CONCLUSION These results suggest the gene-environment interaction between genetic polymorphisms of CYP2E1 & NAT1 and smoking in lung cancer development.