Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: A case–control study in an Indian population

Wang, Jingwen; Jiang, Jing; Zhao, Yang; Gajalakshmi, Vendhan; Kuriki, Kiyonori; Suzuki, Sadao; Nagaya, Teruo; Nakamura, Seiichi; Akasaka, Susumu; Ishikawa, Hideki; Tokudome, Shinkan

doi:10.1016/j.canep.2010.07.003

« Previous Next »Cancer Epidemiology
Volume 35, Issue 1 , Pages 66-72, February 2011

Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: A case–control study in an Indian population

Jingwen Wang
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
- Corresponding author at: Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. Tel.: +81 52 853 8176; fax: +81 52 842 3830.
Jing Jiang
- Department of Hematology and Oncology, The First Hospital, Jilin University, Changchun 130021, China
Yang Zhao
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Vendhan Gajalakshmi
- Epidemiological Research Center, Chennai 600-010, India
Kiyonori Kuriki
- Hygiene and Preventive Medicine, School of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Teruo Nagaya
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Seiichi Nakamura
- Health Research Foundation, Kyoto 606-8225, Japan
Susumu Akasaka
- Osaka Prefectural Institute of Public Health, Osaka 537-0025, Japan
Hideki Ishikawa
- Kyoto Prefectural University of Medicine, Graduate School of Medical Sciences, Kyoto, 602-8566, Japan
Shinkan Tokudome
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
- National Institute of Health and Nutrition, Tokyo 162-8636, Japan

Accepted 2 July 2010. published online 21 July 2010.

Abstract

Background: Susceptibility to sporadic colorectal cancer is multifactorial and arises from interactive combinations of allelic variants in low-penetrance genes and relevant environmental risk factors. Genetic polymorphisms in metabolic enzymes as gene susceptibility factors may modify colorectal cancer risk. We evaluated the risk of colorectal cancer associated with respective or combined glutathione S-transferase (GST) polymorphisms and assessed the interactions between genes and environmental factors in a case–control study in an Indian population. Methods: The study included 59 colon and 243 rectal cancer cases, and 291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR-based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms was estimated by calculation of odds ratios (ORs) and confidence intervals (95% CIs) using unconditional logistic regression. Results: The GSTM1 null genotype was found to be associated with a significantly increased rectal cancer risk (OR=1.55; 95% CI, 1.05–2.30), while the GSTT1 null genotype with a greater risk of colon cancer (OR=2.15; 95% CI, 1.04–4.32). A substantial increase of both colon (OR=10.81; 95% CI, 1.11–107.22) and rectal (OR=4.80; 95% CI, 0.94–35.91) cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1 105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an increased risk for either colon cancer (OR=4.69; 95% CI, 0.84–23.87) or rectal cancer (OR=5.68; 95% CI, 1.79–22.16). Furthermore, the combination of GSTM1 null, GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases. Conclusion: Our results suggest that co-exist of GSTM1 null, GSTT1 null and the variant GSTP1 105Val or 114Val allele may be predisposing risk factors for colorectal cancer in Indian population.