Abstract A47: Meta-analysis of MTHFR polymorphisms in lung cancer: Population health and mutations in the world

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Abstract Purpose: The purpose of this meta-analysis is to identify the associations of methylene-tetra- hydrofolate reductase (MTHFR) gene mutations and smoking as risk factors for lung cancer (LC). LC is the leading cause of cancer-related death worldwide. To-date, population health in relations to the epigenetics pathways is not clearly understood. Inconsistent findings have been cumulated to-date on the case control studies of MTHFR gene mutations in LC around the world. Procedure: On-line databases were searched from PubMed (PM) and PM Central databases for meta-analyses by using a combination of key words including LC, MTHFR, and case control studies. Additional studies were located by cross reference method from located studies. For this analysis, 22 studies published within the last 17 years were identified, containing both control and LC cases of human samples. These papers were reviewed and evaluated using the criteria for the quality of studies by two raters. Relative risks (RR) were calculated for increased or decreased risks for LC. New Data Findings: Preliminary analyses included 11799 cases and 12322 controls associating MTHFR677 locus and LC in 22 studies; 6916 cases and 8526 controls for MTHFR1298 locus in 14 studies. MTHFR677 TT variant as homozygous mutation type was associated with increased LC risk for all race groups combined (pooled RR = 1.151, 95% CI = 1.045 - 1.267, p = 0.004); and also significant for subgroups of Asians (14 studies, RR = 1.080, 1.007 - 1.158, p = 0.031) and Caucasians (8 studies, RR = 1.334, 1.017-1.749, p = 0.037). Asians combined had greater mutation rates on MTHFR677 TT and TC (TT+TC=19.6+47.2=66.8% for cases and 17.8+47.3=65.1% for controls) than Caucasians (11.4+43.4=54.8% for cases and 9.2+41.9%=51.1% for controls). For association of smoking and LC risk, pooled results from 12639 cases and 11828 controls in 17 studies associating MTHFR gene and LC indicated that smoking increased LC risk (pooled RR=1.116, 1.072 - 1.162, P < 0.001). Conclusion: Meta-analyses of epigenetic risk factors associating gene mutations and health behaviors can provide useful insights to improve the quality of future cancer prevention and intervention studies. Further studies are needed to document population-based gene mutations in relation to epigenetics pathways for cancer prevention. Citation Format: Hsiao-Ling Chen, Shyang-Yun Pamela K. Shiao, Linda H. Chiang, Joyce Kusuma. Meta-analysis of MTHFR polymorphisms in lung cancer: Population health and mutations in the world. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A47.