Abstract 5050: A meta-analysis of lifestyle factors with MPO and GSTM1 human genes in lung cancer prevention

Abstract

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