Abstract 4446: Compound gene mutations in the methylation pathway contribute to the chronic health problems and colorectal cancer: A family-based case-control study

Abstract

Abstract The purpose of this project is to examine compound gene mutations in the methylation pathway for their contributions to the development of chronic health conditions and colorectal cancer (CRC) in a family-based case control study. Fifty four cancer patients and matched 54 family controls were recruited from southern California areas by accessing California Cancer Registry data, with racial ethnic groups representing the proportions of population distributions in the communities. Home visits were conducted for interviews and collection of biological samples (buccal and/or blood) for genotyping. Blood plasma samples were processed within 30 minutes of collection, transported on ice, and stored in -80°C for metabolite analyses. Family-Based Association Tests using the FBAT-toolkit, taking account of familial correlations due to shared genes, were performed. The test p-values and beta coefficients were reported. New Data Findings Plasma total homocysteine (tHcy) levels were highest in the advanced cancer group than the early stage cancer group, and control groups with chronic health problems and healthy control (p = 0.0066). For SNP analyses on five selected genes including methylenetetrahydro-folate reductase (MTHFR) 677 and 1298, methionine synthase (MTR) 2756, methionine synthase reductase (MTRR) 66, and dihydrofolate reductase (DHFR) 19 bp deletion, the advanced cancer group had the highest mutation rates for these genes combined, than other groups (p = 0.032), and the most MTHFR mutations (p = 0.016). Among the ethnic groups, the methylation status represented by the SAM/SAH ratio, were lower in African American (AA) and Asian than in Hispanics and Caucasian (p = 0.0199). Caucasian and Hispanics had higher MTHFR mutations than Asian, and AA had the lowest MTHFR mutations (p < 0.001). Hispanics had the lowest mutations (8.7%) on MTR gene (p = 0.069) than Asian (29.3%), Caucasian (41.2%), and AA (50%); and Hispanics had the lowest mutations (26.1%) on MTRR gene (p < 0.001) than Asian (50%), AA (70%), and Caucasian (79.4%). Hispanic samples had the lowest mutations (47.8%) for DHFR 19bp deletion than Caucasian (55.9%), AA (80%), and Asian (85.4%) (p < 0.001). FBAT analyses revealed that SAH levels were associated with MTRR mutation (p = 0.077), but betaine and choline levels were associated with MTR mutations (p < 0.05). Conclusion Based on the findings from these analyses, tHcy levels and common gene mutations in the OCM methylation pathways are associated with the development of chronic health problems and advanced stages of CRC. Ethnic groups present different mutation patterns on the genes in the methylation pathways for population health. These findings warrant personalized healthcare based on gene mutations and enzyme deficiency in the OCM methylation pathways. Citation Format: Pamela Shiao, Brandi Wasek, Teodoro Bottiglieri, Hongyan Xu. Compound gene mutations in the methylation pathway contribute to the chronic health problems and colorectal cancer: A family-based case-control study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4446.