Exploring cancer health disparities through gene-environment interactions:A meta- and pooled analysis of the MTHFR C677T genetic polymorphism and colorectal cancer risk

A14

Background: Colorectal cancer is the second leading cause of cancer-related deaths in the United States and the third most common cancer in adults. Although there have been significant declines in overall cancer death rates, African Americans and other minority populations continue to experience a disproportionate burden of cancer; this health disparity persists after adjusting for various environmental and social factors. Genetics may be the key to better understand the underlying causes of health disparities. The metabolic enzyme 5 10-methelenetetrahydrofolate reductase (MTHFR) has been identified as a key factor in the metabolism of folate, and a common polymorphism C677T of the MTHFR gene has been associated with a lower risk of colorectal cancer in individuals with high levels of folate and low levels of alcohol use. However, few studies about this gene have been conducted in minority populations, especially in African Americans and Latinos. This research is a meta- and pooled analysis of MTHFR polymorphism and colorectal cancer risk focusing on racial/ethnic disparities. 
 Methods: The meta-analysis included twenty-six studies comprising a total of 25,008 subjects (9,603 cases and 15,405 controls). Raw data of the MTHFR polymorphism (CC, CT, and TT genotypes) in cases and controls were extracted from published studies, and the corresponding study-specific crude odds ratios and 95 percent confidence intervals were calculated for colorectal cancer risk. The Genetic Susceptibility to Environmental Carcinogens (GSEC) database was used for the pooled analysis. This collaborative project collects information on metabolic gene polymorphisms and cancer from published and unpublished case-control studies. At the time of enrollment each investigator completed a standardized questionnaire regarding but not limited to study design, laboratory methods used for genotyping, and source of DNA for genotype analysis. Fourteen studies were included in the pooled analysis for a total of 12,061 subjects (4443 cases and 7395 controls).
 Results: The overall meta-estimate of the odds of colorectal cancer with genotype TT compared to genotype CC was 0.81 (95%CI: 0.74, 0.88). There were no statistically significant differences between ethnicities. The pooled analysis was used to further explore differences by race/ethnicity. Preliminary analysis of the pooled data shows the pooled-estimate of the odds of colorectal cancer with genotype TT versus CC in Asians was 0.69 (95%CI: 0.56, 0.86), Caucasians, 0.92 (95%CI: 0.78, 1.09), and African-Americans, 1.04 (95%CI: 0.45, 2.38); while for Latinos, the OR with genotype CT versus CC was 1.20 (95%CI: 0.81, 1.79). The frequency of the TT variant genotype in controls was 14% in Caucasians, 17% in Asians, 5% in African-Americans and 23% in Latinos.
 Conclusions: This analysis supported conclusions that homozygosity for the T allele (MTHFR 677TT polymorphism) was associated with a reduced risk of colorectal cancer risk, but this may not hold true in Latino populations. This may be partly due to the observed difference in genotype prevalence with ethnicity. Exploring the MTHFR C677T polymorphism and behavioural and environmental determinants that influence colorectal cancer risk may help us to better understand how this risk impacts different minority populations.