GSTT1 and GSTM1 Null Genotypes and the Risk of Gastric Cancer: A Case-Control Study in a Chinese Population 1 Veronica Wendy Setiawan, Zuo-Feng Zhang, 2 Guo-Pei Yu, Yong-Liang Li, Ming-Lan Lu, Chiao-Jung Tsai, Derek Cordova, Ming-Rong Wang, Chun Hua Guo, Shun-Zhang Yu, and Robert C. Kurtz Department of Epidemiology, University of California-Los Angeles School of Public Health, and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-1772 [V. W. S., Z-F. Z., C-J. T., D. C.]; Biostatistics and Epidemiology Service, New York Eye and Ear Infirmary, New York, New York 10003 [G-P. Y.]; School of Public Health, Columbia University, New York, New York 10032 [Y-L. L.]; Department of Pathology [M-L. L.] and Gastroenterology and Nutrition Service, Department of Medicine [R. C. K.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021; Yangzhong County Anti-Epidemic Station, Yangzhong County 212200, People’s Republic of China [M-R. W., C. H. G.]; Department of Epidemiology, School of Public Health, Shanghai Medical University, Shanghai 200032, People’s Republic of China [S-Z. Y.] Abstract Glutathione S-tranferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 ( class) and GSTM1 ( class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01– 6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75–7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population. Introduction Despite the downward trend in incidence and mortality in most countries, gastric cancer was recently estimated to be the sec- ond most common cancer in the world after lung cancer. Thirty- five percent of worldwide cases occur in China, where it re- mains the most common cancer in both sexes, as it is elsewhere in Eastern Asia. Gastric cancer remains the most frequent cancer in men (ahead of lung cancer) in tropical South America, and high rates are also present in both sexes in the former Union of Soviet Socialist Republics (1). The etiology of gastric cancer is not well established, although nutritional (excessive salt intake and deficient vegetable/fruit intake), microbial (H. pylori infection), and genetic factors have been suggested in a multi- step and multifactorial process (2). The glutathione S-tranferase supergene family consists of four gene subfamilies (GSTA, GSTM, GSTT, and GSTP) that play a central role in the inactivation of toxic and carcinogenic electrophiles (3, 4). Certain genes within the GSTM and GSTT (GSTM1 and GSTT1) subfamilies exhibit homozygous deletion (null genotype) polymorphisms that have been considered as potentially important modifiers of individual risk of environ- mentally induced cancers (5). The prevalence of the null gen- otype of GSTM1 and GSTT1 has been found to vary among ethnic groups (6). The GSTM1 is absent in 35– 60% of indi- viduals (7–9), and GSTT1 is absent in 10 – 65% of the human population (6, 9). Research on the relationship between ho- mozygous deletion polymorphisms and the risk of cancer is important for a better understanding of interindividual variation in response to carcinogen exposures and cancer susceptibility. Previous studies have shown that the GSTM1 null geno- type has been associated with an increased susceptibility to lung cancer (10 –14), bladder cancers (7, 15), and cutaneous cancers (16). Studies with regard to an association between GSTM1 and gastric cancer have been limited, and the results have been inconsistent (17, 18). GSTT1 null genotype may be a risk modifier in the oc- currence of colorectal cancer, and it is suggested that this Received 6/7/99; revised 10/29/99; accepted 11/6/99. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported in part by NIH National Cancer Institute, Department of Health and Human Services, Grants CA77954, CA09142 (to Z-F. Z), and CA16042, by a seed Grant by University of California-Los Angeles Jonsson Cancer Center Foundation, and by the Weissman Fund. 2 To whom requests for reprints should be addressed, at Department of Epide- miology, University of California-Los Angeles School of Public Health, 71-225 CHS, Box 951772, Los Angeles, CA 90095-1772; Phone: (310) 825-8418; Fax: (310) 206-6039; E-mail: ZFZHANG@UCLA.EDU. 73 Vol. 9, 73– 80, January 2000 Cancer Epidemiology, Biomarkers & Prevention Research. on November 27, 2021. © 2000 American Association for Cancer cebp.aacrjournals.org Downloaded from