Abstract B08: Meta-analyses of methionine-related polymorphisms and colorectal cancer risk for population health

Introduction/Purpose: The purpose of this meta-analysis is to determine the associations between the methionine related polymorphisms and the risk of developing colorectal cancer (CRC) for population health. CRC accounts for over 9% of all cancer incidences, is the third most common cancer worldwide, and accounts for the third leading cause of cancer related deaths. Studies have been published to support the important roles of methionine synthase (MTR), and methionine synthase reductase (MTRR) as key enzymes involved in DNA synthesis, repair, and methylation. However, the associations between these methionine-related polymorphisms and the risk of CRC have been inconsistent. Previous meta-analyses on these genes had mixed findings, without clear identification of mutation rates per population groups. Procedure: On-line databases were searched from PubMed (PM) and PM Central databases for meta-analyses by using a combination of key words including methionine synthase or MTR, methionine synthase reductase or MTRR, colorectal or colon or rectal and cancer or carcinoma, and case control studies and meta-analysis. The located papers were cross referenced to find all original studies. For this analysis, 68 studies of human samples published within the last 16 years were located. Following the exclusions of the non-original research and non-case control studies, 34 studies remained. 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 CRC. New Data Findings: Preliminary data analysis included 15377 cases and 22445 controls for MTR2756 in 27 studies with 31 race-ethnic groups; and 11594 cases and 16665 controls for MTRR66 in 20 studies with 22 race-ethnic groups. MTRR66 AA subtype was associated with increased CRC risk for Asian-Japanese group (RR = 1.0824, 95% CI = 1.01 – 1.05, p = 0.0165, 1696 cases and 2355 controls in 4 studies); whereas MTRR66 AG subtype was protective against CRC risk for Asian-Japanese group (RR = 0.9236, 0.86 – 0.99, p = 0.0358, 1696 cases and 2355 controls in 4 studies). MTR2756 GG subtype for the Western countries was protective against CRC approaching statistical significance (RR = 0.9107, 0.81-1.02, p = 0.0997, 13485 cases and 19317 controls in 26 study groups). The mutation rates for MTR2756 for all populations were distributed very closely between Western countries and Asian-Japanese groups (overall GG=3.7% for cases and 4% for controls, AG=30.7% for cases and 30.9% for controls, GG+AG=34.4% for cases and 34.9% for controls). The mutation rates for MTRR66 were greater in western countries than Asian-Japanese group (Western countries GG=29% for cases and 28.9% for controls, AG=48.7% for both cases and controls, GG+AG=77.7% for cases and 77.6% for controls; Asian-Japanese GG=8.6% for cases and 9.2% for controls, AG=41.1% for cases and 44.1% for controls, GG+AG=49.7% for cases and 53.3% for controls). Conclusion: Different gene mutation rates across populations may be accredited to the differences in racial origin of the populations, the lifestyle, and the pattern of diet in the respective countries. Further studies are needed to evaluate the associations related to epigenetics pathways and gene-environment interactions for cancer prevention. Citation Format: Carolyn Du, Pamela K. Shiao, Yen-Chun Lin. Meta-analyses of methionine-related polymorphisms and colorectal cancer risk for population health. [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 B08.