Abstract
Glutathione S-transferases (GSTs) are a family of important enzymes involved in the detoxification of a wide variety of known and suspected carcinogens, including potential mammary carcinogens identified in charred meats and tobacco smoke. A substantial proportion of the Caucasian population has a homozygous deletion (null) of the GSTM1 or GSTT1 gene, which results in lack of production of these isoenzymes. We conducted a case-control study in a cohort of postmenopausal Iowa women who in 1986 completed a mailed questionnaire on lifestyle factors including information on cigarette smoking and breast cancer risk factors. DNA samples and information related to charred meat intake were obtained, in the case-control study, from breast cancer cases diagnosed during 1992–1994, and a random sample of cancer-free cohort members. Included in this study were 202 cases and 481 controls who were genotyped for GSTM1 or GSTT1 gene polymorphisms. Compared to women who had both GSTM1 and GSTT1 genes, a 60% elevated risk (95% CI = 1.0–2.5) was observed among those whose GSTM1 or GSTT1 gene was deleted. When stratified by meat eating habits, the risk of breast cancer associated with null GSTM1 or GSTT1 genotype was observed primarily among women who ate meats consistently well- or very well-done. Women who carried either one of the null genotypes and consumed meat consistently well- or very well-done had a 3.4-fold elevated risk of developing breast cancer (95% CI = 1.6–7.1). Cigarette smoking was not a risk factor for breast cancer among women who had either the GSTM1 or GSTT1 genes. Among those with the null GSTT1 genotype, however, a significantly elevated risk of breast cancer was associated with cigarette smoking (OR = 2.5, 95% CI = 1.1–5.4) and the association was stronger among former (OR = 4.4, 95% CI = 1.5–12.8) than current smokers (OR = 1.3, 95% CI = 0.4–4.1). This study suggests that certain null GST genotypes may be associated with an elevated risk of breast cancer and the association may be modified by charred meat intake and cigarette smoking.
Similar content being viewed by others
References
Hayes JD, Pulford DJ: The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30: 445–600, 1995
Hengstler JG, Arand M, Herrero ME, Oesch F: Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent Results Cancer Res 154: 47–85, 1998
Rebbeck TR: Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomark Prev 6: 733–743, 1997
el-Bayoumy K: Environmental carcinogens that may be involved in human breast cancer etiology. Chem Res Toxicol 5: 585–590, 1992
Wolff MS, Collman GW, Barrett JC, Huff J: Breast cancer and environmental risk factors: epidemiological and experimental findings. Ann Rev Pharm Tox 36: 573–596, 1996
Helzlsouer KJ, Selmin O, Huang H, Strickland PT, Hoffman S, Alberg AJ, Watson M, Comstock GW, Bell D: Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J Natl Cancer Inst 90: 512–518, 1998
Bailey LR, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl FF: Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58: 65–70, 1998
Charrier J, Maugard CM, LeMevel B, Bignon YJ: Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility. Br J Cancer 79: 346–353, 1999
Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK: Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14: 1821–1824, 1993
Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Laughlin R, Nemoto T, Michalek AM, Harrington A, Ford TD, Shields PG: Chtochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and post-menopausal breast cancer risk. Cancer Res 55: 3483–3485, 1995
Garcia-Closas M, Kelsey KT, Hankinson SE, Spiegelman D, Springer K, Willett WC, Speizer FE, Hunter DJ: Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility. J Natl Cancer Inst 91: 1960–1964, 1999
Kelsey KT, Hankinson SE, Colditz GA, Springer K, Garcia-Closas M, Spiegelman D, Manson JE, Garland M, Stampfer MJ, Willett WC, Speizer FE, Hunter DJ: Glutathione Stransferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol Biomark Prev 6: 511–515, 1997
Mitrunen K, Jourenkova N, Kataja V, Eskelinen M, Losma V-M, Benhamou S, Vainio H, Uusitupa M, Hirvonen A: Gluta thione S- transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer. Cancer Epidemiol Biomark Prev 10: 229–236, 2001
Millikan R, Pittman G, Tse C-K, Savitz DA, Newman B, Bell D: Glutathione S-transferases M1, T1, and P1, and breast cancer. Cancer Epidemiol Biomark Prev 9: 567–573, 2000
Zheng W, Gustafson DR, Sinha R, Cerhan JR, Moore D, Hong C, Anderson KE, Kushi LH, Sellers TA, Folsom AR: Welldone meat intake and the risk of breast cancer. J Natl Cancer Inst 90: 1724–1729, 1998
Palmer JR, Rosenberg L: Cigarette smoking and the risk of breast cancer. Epidemiol Rev 15: 145–156, 1993
Ambrosone CB, Shields PG: In: Bowcock AM (ed) Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics. Humana Press, Totowa, NJ, 1999, pp. 519–536
Folsom AR, Kaye SA, Sellers TA, Hong C, Cerhan JR, Potter JD, Prineas RJ: Body fat distribution and 5-year risk of death in older women. JAMA 269: 483–487, 1993
Sellers TA, Kushi LH, Potter JD, Kaye SA, Nelson CL, McGovern PG, Folsom AR: Effect of family history, body-fat distribution, and reproductive factors on the risk of postmenopausal breast cancer. N Engl J Med 326: 1323–1329, 1992
Sinha R, Gustafson DR, Kulldorff M, Wen W-Q, Cerhan JR, Zheng W: 2-Amino-1methyl-6-phenylimidazo [4, 5-b]-pyridine, a carcinogen in high-temperature-cooked meat, and breast cancer risk. J Natl Cancer Inst 92: 1352–1354, 2000
Zheng W, Deitz AC, Campbell DR, Wen W, Cerhan JR, Sellers TA, Folsom AR, Hein DW: N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk. Cancer Epidemiol Biomark Prev 8: 233–239, 1999
Deitz AC, Zheng W, Leff MA, Gross M, Wen WQ, Doll MA, Ziao GH, Folsom AR, Hein DW: N-acetyltransferase-2 genetic polymorphism well-done meat intake, and breast cancer risk among postmenopausal women. Cancer Epidemiol Biomark Prev 9: 905–910, 2000
Zheng W, Xie D, Cerhan JR, Sellers TA, Wen W, Folsom AR: Sulfotransferase 1A1 (SULT1A1) polymorphism, endogenous estrogen exposure, well-done meat intake, and breast cancer risk. Cancer Epidemiol Biomark Prev 10: 89–94, 2001
Richards B, Skoletsky J, Shuber AP, Balfour R, Stern RC, Dorkin HL, Parad RB, Witt D, Klinger KW: Multiplex PCR amplification from CFTR gene using DNA prepared from buccal brushes/swabs. Hum Mol Genet 2: 159–163, 1993
Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB: Human glutathione Stransferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300: 271–276, 1994
Nagao M, Ushijima T, Wakabayashi K, Ochiai M, Kushida H, Sugimura T, Hasegawa R, Shirai T, Ito N: Dietary carcinogens and mammary carcinogenesis: induction of rat mammary carcinomas by administration of heterocyclic amines in cooked foods. Cancer (suppl) 74: 1063–1069, 1994
Adamson RH: Cancer Prevention. J.B. Lippincott, Philadelphia, 1990, pp. 1–7
Kazerouni N, Sinha R, Hsu CH, Greenberg A, Rothman N: Benzo[a]Pyrene content in selected food samples. Proc Amer Assoc Cancer Res 40: 152, 1999
Lijinsky W: The formation and occurrence of polynuclear aromatic hydrocarbons associated with food. Mutat Res 259: 251–261, 1991
O'Neill IK, Chen J, Barsch H: Relevance to Human Cancer of N-Nitroso Compounds, Tobacco Smoke and Mycotoxins. IARC Scientific Publication No. 105, Lyon: International Agency for Research on Cancer, 1991
Knekt P, Steineck G, Jrvinen R, Hakulinen AA: Intake of fried meat and risk of cancer: a follow-up study in Finland. Int J Cancer 59: 756–760, 1994
Ronco A, De Stefani E, Mendilaharsu M, Deneo-Pellegrini H: Meat, fat and risk of breast cancer: a case-control study from Uruguay. Int J Cancer 65: 328–331, 1996
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zheng, W., Wen, WQ., Gustafson, D.R. et al. GSTM1 and GSTT1 polymorphisms and postmenopausal breast cancer risk. Breast Cancer Res Treat 74, 9–16 (2002). https://doi.org/10.1023/A:1016005100958
Issue Date:
DOI: https://doi.org/10.1023/A:1016005100958