Abstract B05: GSTM1 as risk factor for breast cancer: Meta-analysis of 57 studies

Abstract

Purpose: To examine the association of glutathione S-transferase Mu 1 (GSTM1) and other risk factors for breast cancer. Breast cancer is the most common malignancy and the second leading cause of cancer death among women in the United States. As identified from the most recent genome-wide association studies (GWAS) and meta-analyses, GSTM1 is listed as one of the most published breast cancer genes for various race-ethnicities. GSTM1 present/null genotypes are low-penetrance cancer susceptibility genes; and these types of genes acting together with endogenous and lifestyle risk factors, account for majority of breast cancers. GSTM1 plays a key role in detoxification of environmental carcinogens such as smoking and alcohol, steroid hormone metabolism, and deoxyribonucleic acid (DNA) damage repair pathways. Procedure: PubMed databases were search with key words “breast cancer” and “GSTM1” up to the most recent publications. Full texts of 158 articles were reviewed. Articles were selected based on the following criteria: a) evaluation of the GSTM1 present/null gene variation and breast cancer risk, b) case-control studies, c) sufficient published data for estimating relative risk (RR) with 95% confidence interval (CI). All selected publicationswere evaluated and scored for quality using the rating indicators from Quality of Reporting of Meta-analyses (QUOROM) framework. Based on the sets of criteria, studies with poor quality rating score and repeated use of data from the same authors are excluded from meta-analyses. The sets of criteria for quality provided an objective measure for inclusion of studies in meta-analysis, which enhanced rigor of research. An inter-rater reviewed the selection of publications and quality data rating scores. Total of 57 studies with 17,102 cases and 17,932 controls were included in meta-analysis. These studies included samples from different race-ethnicities worldwide. Findings: In the overall pooled analysis, GSTM1 present genotype significantly decreased breast cancer risk (RR = 0.96, 95% CI = 0.93 to 0.99, p = 0.01) suggesting its protective effect. The same findings of decreased breast cancer risk with present genotype were noted for Caucasians (RR = 0.96, 95% CI = 0.92 to 0.99, p = 0.02). On the other hand, significantly elevated breast cancer risk was associated with GSTM1 null genotype when all studies were pooled into meta-analysis (RR = 1.05, 95% CI = 1.01 to 1.08, p = 0.009). In the subgroup analysis by ethnicity, significantly increased risks were found in Asians (RR = 1.11, 95% CI = 1.02 to 1.21, p = 0.02). These findings support that individuals with GSTM1 null genotype are more susceptible to DNA damage and carcinogenesis. Lifestyle behaviors such as smoking, alcohol intake, and diet low in isothiocyanates (ITCs) (i.e. cruciferous vegetables and fibers) were significantly associated with GSTM1 genotypes and breast cancer risk. The protective effects of dietary ITCs were seen more on individuals with GSTM1 null genotype than those with GSTM1 positive. Conclusion: This meta-analysis suggests that the GSTM1 null genotype is a low-penetrant risk factor for developing breast cancer and the present genotype is protective for breast cancer development. Future in-depth researches are necessary to understand gene-environment interactions including lifestyle behaviors that may elucidate inconsistent findings of previous studies. The outcome of the study can provide useful insights of GSTM1 as risk factor for breast cancer, which can further generate useful evidence for larger studies in different populations. Identification of protective GSTM1 genotype and lifestyle behaviors are useful in laying out the foundation for cancer prevention through innovative behavioral interventions. Citation Format: Mildred C. Gonzales, Pamela Shiao, Amanda Lie, Ching-Yi Chiu, Maria Suarez. GSTM1 as risk factor for breast cancer: Meta-analysis of 57 studies. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B05.