Glutathione S-transferases M1, T1, and P1 and Breast Cancer: A Pooled Analysis

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 13; no. 9; pp. 1473 - 1479
• Main Authors: Vogl, Florian D, Taioli, Emanuela, Maugard, Christine, Zheng, Wei, Pinto, Luis F Ribeiro, Ambrosone, Christine, Parl, Fritz F, Nedelcheva-Kristensen, Vessela, Rebbeck, Timothy R, Brennan, Paul, Boffetta, Paolo
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-09-2004
• Subjects: Acyltransferases - genetics; Base Sequence; Biological and medical sciences; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Carcinogens, Environmental - pharmacokinetics; Carcinogens, Environmental - toxicity; Case-Control Studies; Chromosome Deletion; Codon; DNA Mutational Analysis; Female; Genetic Carrier Screening; Genetic Predisposition to Disease - genetics; Genotype; Glutathione Transferase - genetics; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Meta-Analysis as Topic; Polymorphism, Genetic - genetics; Risk Factors; Tumors; Human; Genetic variability; Enzyme; Isozyme; Transferases; Tobacco smoking; Genotype; Breast cancer; Malignant tumor; Epidemiology; Mammary gland diseases; Reproduction; Cancerology; Glutathione transferase; Risk factor; Genetics; Public health
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.1473.13.9

The glutathione S -transferase ( GST ) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile→Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential
effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study
on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and
95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification
on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were
analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86–1.12) with the GSTM1 null, 1.11 (0.87–1.41) with the GSTT1 null, 1.01 (0.79–1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62–1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables,
nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms
in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with
smoking or reproductive history to modify cancer risk.