Glutathione S transferase mu 1 (GSTM1) gene has been associated with lung cancer (LC) risk, for GSTM1 enzyme playing a vital role in detoxification pathway and protective against toxic insults. The major objective of this study was to investigate GSTM1 deletion pattern and its association with LC in the world’s population by using meta-prediction techniques. The secondary objective was to examine the effects of air pollution, smoking status, and other factors for gene-environment interactions with GSTM1 deletion and LC risk. We completed a comprehensive search to yield a total of 170 studies (40,296 cases and 48,346 controls) published from 1999 to 2017 for meta-analyses. The results revealed that GSTM1 deletion type was associated with increased risk of LC, while GSTM1 present type provided protective effect for all populations combined worldwide. Subgroup analysis on the rank order of risks from highest to lowest, among racial–ethnic groups, were Chinese, South East Asian, other North Asian, European, and finally American. Additional predictive analyses presented that air pollution played a significant role with increased risks of GSTM1 deletion and LC susceptibility, and the risks increased for smokers with higher levels of air pollution. Based on the findings of meta-predictive analysis, increased air pollution levels and smoking status presented additive effects to the LC risk susceptibilities and GSTM1 gene polymorphisms, for gene-environment interactions. Future studies are needed to examine gene-environment interactions for GSTM1 interacting with environmental factors and dietary interventions to mitigate the toxic effects, for LC prevention.

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Purpose: Lung cancer (LC) is a worldwide public health problem and a leading cause of death in both men and women. Its development is attributed to epigenetic factors, including smoking, diet, and occupation that can be modified. Glutathione S-transferase that belongs to the mu class (GSTM1) and myeloperoxidase (MPO) gene polymorphisms have been cumulating in the literature, associating lifestyle factors and LC development. Thus, a meta-analysis was conducted to examine the associations of lifestyle factors with GSTM1 and MPO genes for LC prevention. Procedure: Literature searcheswere completed by searching at three different times using keyword related to human GSTM1, MPO, and LC. Quality of the studies were rated based the standards of Quality of Reporting of Meta-analysis. Inter-rater evaluation on data coding was completed to ensure data accuracy. Pooled relative risks (RR) was computed to determine the association of factors with LC. Findings: Preliminary analyses included 28,831 cases and 35,069 controls associating smoking with LC in 98 studies; with 5,938 cases versus 6,668 controls nested in 20 studies with MPO gene counts, and 7,101 cases and 9,396 controls nested in 32 studies with GSTM1 gene counts respectively. Smoking status was associated with increased LC risk in all populations (RR = 1.40, p < 0.0001), and for subgroups of Whites (46 studies), Asians (38 studies) and Euramerican mixed race groups (12 studies) (all p < 0.0001); whereas, no smoking status was protective for LC prevention in all race subgroups (P < 0.0001). GSTM1 present type as compared to null type was more protective in nonsmoking subjects (RR = 0.35, p < 0.05 vs. RR = 0.45, p < 0.0001) and smoking subjects (RR = 1.25 vs. RR - 1.42, both p < 0.0001). Among the studies with MPO gene counts, nonsmoking status was protective (RR = 0.49) and smoking status increased risk for LC (RR = 1.29) (both p < 0.0001); with AA subtype in nonsmoking subjects being protective, and GG subtype in smoking subjects increased risk for LC (both p < 0.05). Low vegetable intakes were associated with increased LC risk (RR = 1.26, P < 0.05) in 7 studies, and included fiber intake, cruciferous vegetables or any vegetable intake. Conclusion: Following the meta-analysis of these studies, it can be recommended that primary epigenetic prevention of LC could include environment free from tobacco smoking and having a diet rich in isothiocyanates or vegetable intake. These preventive measures are important in attenuating oxidative stress for healthy methylation pathways to reduce the risk factors of LC. Citation Format: PoJui Paula Yu, S. Pamela Shiao, Maria Suarez. A meta-analysis of lifestyle factors with MPO and GSTM1 human genes in lung cancer prevention. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5050. doi:10.1158/1538-7445.AM2014-5050

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.