Cancer Research and Treatment

Original Articles

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

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.

Citations

Citations to this article as recorded by

Polymorphism and transcriptional regulation of GSTP1 in cancer and other human diseases
Qi-Ran Zeng, Xiao-Shuai Du, Ruo-Xi Zhao, Dian Yang, Zhi-Yuan Yang, Yang Liang, Hai-Fan Yu
International Journal of Biological Macromolecules.2026; 346: 150588. CrossRef
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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Immunohistochemical and Genetic Changes in Putative Preneoplastic Lesion in Rat Liver: Kye Yong Song, Dae Young Kim, Hyung Chun Kim, Mi Kyung Kim, Young Ho Rha, Sang Chul Park; J Korean Cancer Assoc. 1990;22(3):395-410.

Abstract PDF: Immunohistochemical and electron microscopic studies were carried out on the preneoplastic nodule, to observe the morphological and immunohistochemical changes of the transformed preneo- plastic hepatacytes by immunohistochemical method using antibodies to the various marker enzymes such as glutathione S-transferase of placental form (GST-P), glutathione S-transferase of basic form (GST-L), Glucose 6 phosphate dehydrogenase (G6PDH), gamma glutamyl transpeptidase (GGT) The results obtained were as follaws; l) The transformed preneoplastic hepatocytes could be detected easily by use af GST-P antibody especially in the clear cell nodule from the 2nd month and is significantly increased from the 12th month compar'ed with the 2nd month, while basophilic nodule was observed from the 10th month. 2) Immunohistochemical staining revealed strong positive reaction to GST-P and weakly positive to G6PDB, GST-L and focally poitive to GGT in clear cells, while weak or negative reaction to GST-P, G6PDH, GST-L and GGT in eosinophilic cells. and Basophilic cells showed negative reaction to GST-P, GST-P, GST-L, G6PDH and positive to GGT. 3) Electron microscopically, clear cells revealed abundant glycogen particles and well developed endoplasmic reticulum, while eosinophilic cell reveaied abundant mitochondria and vacuoles with a few glycogen, basophilic cells revealed abundant rER and ribosomes. Immunohistochemically, GST-P is abundantly distributed in the cytoplasm especially around the rER, vesicles and alsp in nucleus. 4) Therefore, glutathione S-transferase is a good marker for early detection of genetically transformed and preneoplastic hepatacytes especially clear cell while GGT is positive marker for basophilic cell. GST-P is abundantly present in the cytosol and around the rER and vesicle. The clearness of preneoplastic hepat.ocytes were thought as the result of marked increase of glycogen while basophilic cells were the result of marked incresed rER.

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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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Glutathione S-Transferase Polymorphisms and Genetic Susceptibility to Cervical Cancer: Jin Woo Kim, Chun Geun Lee, Yeo Won Sohn, Hong Ki Min, Su Mi Han, Eun Young Cho, Kyung Sook Kim, Jin Woong Shin, Sa Jin Kim, Tae Chul Park, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(4):673-680.

Abstract PDF: PURPOSE
The identification of genetic traits that predispose individuals to environmentally induced cancers is one of the challanges in the assessment of individual cancer risk. The genetically determined differences in metabolism, related to glutathione S-transferases (GSTs) have been reported to be associated with various cancer susceptibility. The present study was set up to establish the frequencies of the polymorphic genotypes of two GST (GST- mu and GST-theta) isozymes in Korea, to evaluate a possible increased incidence of the genotypes associated with higher cervical cancer risks among Korean cervical cancer patients.
MATERIALS AND METHODS
In this study, extracted DNAs from cervical cancer patients (228 for GST-mu and 241 for GST-theta genotypes) and normal controls (360 for GST-mu and 353 for GST-theta genotypes) were analysed with the polymerase chain reaction (PCR).
RESULTS
The overall genotype distribution of the GST-theta polymorphisms was not statistically different between the patients and control groups. But, in the GST-mu null genotypes, there were remarkable differences between patients and control groups when the cervical cancer patients were devided into subgroups with respect to the age. The frequency of GST-mu null polymorphisms in the cervical cancer patients under the 40 years old was significantly higher compared to the patients above the 40 years old (0.01CONCLUSION
These results strongly suggest that individuals carrying GST-mu (null) alleles are genetically susceptible to cervical cancer which develops before 40 years of age and GST-mu null genotype may play a some role in cervical cancer progression.

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The Risk of Gastric Cancer in Koreans according to Smoking, Drinking, Diet, and the Genetic Polymorphisms of Glutathione S-Transferases and L-myc Protooncogene: Jin Woo Park, Young Jin Song, Hyo Yung Yun, Heon Kim, Yoon Ok Ahn, Sang Joon Kim, Jin Pok Kim, Jong Won Kang, Hong Mei Nan, Yong Dae Kim; J Korean Cancer Assoc. 2000;32(6):997-1006.

Abstract PDF: PURPOSE
This study was performed to investigate the interaction of genetic polymorphisms of glutathione S-transferases and L-myc proto-oncogene with smoking, drinking, and dietary factors in the carcinogenesis of gastric cancer.
MATERIALS AND METHODS
Two hundred and four gastric cancer patients and 1:1 matched hospital controls were the study subjects. They were interviewed with a questionnaire including alcohol consumption, smoking and dietary habit. We investigated genetic polymorphisms of GSTM1, GSTT1 and L-myc genes using PCR-RFLP techniques.
RESULTS
Smoking and soybean paste stew were risk factors and doughnut, fried potato, welsh onion, rice cake, seaweed, slices of raw fish, melon, tomato, garlic and onion were protective factors of gastric cancer. The odds ratios of some food items changed significantly according to the genotypes; green vegetables and pork according to the GSTM1 genotype; pork, soybean curd, steamed or hard-boiled soybean and welsh onion according to the GSTT1 genotype; rice cake and garlic according to the L-myc proto-oncogene genotype.
CONCLUSION
These results suggest that the genetic polymorphisms of GSTM1, GSTT1 and L-myc genes might modify the effects of environmental factors on gastric cancer possibly by engaging in the metabolism of food, alcohol and cigarette smoke.

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