Abstract A02: Meta-analyses of MPO, EGFR, and GSTM1 genes as risk factors for lung cancer prevention

Purpose: The purpose of this meta-analysis was to identify genes that have been associated with lung cancer (LC), and the risk factors associated with these genes for cancer prevention. LC is the leading cause of cancer related deaths worldwide. Three genes identified through the genome application framework, and well published in the literature, are Myeloperoxidase (MPO), a receptor for members of the epidermal growth factor (EGFR) family, and a glutathione S-transferase that belongs to the mu class (GSTM1). Findings from previous meta-analyses on this topic published from 10 years ago to 2 years ago were mixed with inconsistent and controversial findings. Since then, additional literature showed identification of the potential risk factors for the application of cancer genome and LC prevention. Procedure: On-line literature were searched from PubMed (PM), PM Central, PM Health databases for systematic reviews and meta-analyses by using a variety of combinations of key words about LC genes, cancer prevention, human models, and clinical trials. For this analysis, 61 studies were identified that have been published within the last 15 years and included data containing both control and LC cases of human samples. These papers were reviewed and evaluated using the criteria for the quality of studies. These studies included 20, 22, and 19 studies on MPO, EGFR and GSTM1 respectively. Summary of Data Findings: Preliminary analyses included 83,711 cases and 16,256 controls associating these genes with LC; with 6,363, 7,192, and 70,156 LC cases versus 7,3,46, 7,532, and 1,378 controls for MPO, EGFR and GSTM1 respectively. These studies included samples of all races and many ethnicity groups, and both genders. For prevention, these three genes each have unique metabolic mechanisms and major single nucleotide polymorphisms (SNPs) associated with the prognosis and treatment effects of LC. MPO is released from neutrophils in response to various pulmonary insults such as tobacco smoking and chemicals that produce air populations, thus, smokers and industrial workers have worse prognosis. Specifically, the MPO SNP, G-463A (rs2333227) has been significantly associated with LC risk. EGFR protein production including activating somatic mutations (exon 19 deletion and exon 21 L858R) may be different across gender and racial ethnic groups and demonstrate different sensitivity in non-smokers. Thus, prevention and treatments targeting EGFR may be considered in preference to other cancer treatments. Those with LC and SNPs of GSTM1 type have been found to be highly influenced by the dietary intake of cruciferous vegetables or fruits and green teas for the prognosis, especially for individuals who are susceptible for oxidative stress and oxidative DNA damage. Conclusion: Following analysis of these studies, it can be recommended that primary prevention of LC could include having a diet rich in antioxidants, and avoiding tobacco smoking and air pollution in environmental exposures. Meta-analysis of these studies has important impact for healthy lifestyles, health habits and screening. Maintenance of healthy lifestyles includes avoiding tobacco smoking or second hand smoking, and inhaling air pollutants; and taking a nutritional diet rich in antioxidants such as cruciferous vegetables or fruits and green teas. These preventive application measures are important in attenuating oxidative stress and DNA damage to reduce the risk factors of LC for the general public. Citation Format: Nick DeVries, S. Pamela Shiao, Melissa J. LaBonte, Ching-Yi Chiu, Linda H. Chiang, Rose Sakamoto. Meta-analyses of MPO, EGFR, and GSTM1 genes as risk factors for lung cancer prevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A02.