Abstract 5058: MTHFR and health behaviors: A meta-analysis of epigenetic risks for breast cancer prevention

Abstract

Abstract Purpose: Breast cancer is the most common malignancy and the second leading cause of cancer death among women worldwide. Methylenetetrahydrofolate reductase (MTHFR) is one of the most studied low penetrant genes that are critical for methylation pathways for deoxyribonucleic acid (DNA) repair and normal cellular development. Methylation pathways are affected by health behaviors such as folate intake, alcohol consumption, and tobacco smoking. While there were several meta-analyses on the associations of MTHFR gene variations and BC, by far, no meta-analysis has been noted on the associations of health behaviors and MTHFR gene variations, with breast cancer. Procedure: PubMed databases were searched by using a combination of key words including “breast cancer”, “MTHFR”, “folate”, “alcohol”, “smoking”, and “health determinants”. Initial search resulted 135 articles from 1999 to 2013. Studies were reviewed for case-control studies, and scored for quality using the standard rating indicators from Quality of Reporting of Meta-analyses. Repeated data from same authors and those with poor quality scores were excluded. Inter-rater reliabilities on data coding and quality scores were established for the selection of studies. Findings: Preliminary results included 55 studies for a total of 22,077 breast cancer cases and 25,419 controls including 27 studies with Whites, 21 studies with Asians, and 7 studies with mixed Euramericans. Twelve studies included MTHFR gene counts with folate intake levels for 8,032 cases and 10,482 controls; 5 studies with alcohol consumption for 3,068 cases and 5,157 controls; and 5 studies with tobacco smoking status for 909 cases and 1233 controls. Preliminary analysis indicated that MTHFR 677CT was associated with increased risk of BC (P < 0.005). The results also suggested that low folate intake, heavy alcohol consumption, and tobacco smoking contributed to increased risks for BC. Conclusion: Investigating the epigenetic risks including healthy life style factors in relation to gene variations has the potential to explain the influence of health behaviors on carcinogenesis. Translating the results from the meta-analysis of health behaviors in relation to epigenetics can provide meaningful insights on the prevention of breast cancer. The findings from the meta-analysis per various race-ethnicity groups can be useful for future development of culturally sensitive and personalized interventions to prevent and reverse breast cancer by promoting the healthy methylation pathways for cancer prevention. Citation Format: Mildred Crisostomo Gonzales, S. Pamela Shiao, Amanda Lie. MTHFR and health behaviors: A meta-analysis of epigenetic risks for breast 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 5058. doi:10.1158/1538-7445.AM2014-5058