Abstract B01: Meta-analyses of MTHFR and UGT1A1 genes as risk factors for colorectal cancer prevention
Authors: Lie Amanda , Shiao S. Pamela , LaBonte Melissa J. , Chiu Ching-Yi , Chiang Linda H. , Sakamoto Rose 
Published: January 2014

Purpose: The purpose of this meta-analysis was to identify genes that have been associated with colorectal cancer (CRC), and the risk factors associated with these genes for cancer prevention. CRC is the third leading cause of cancer related deaths worldwide. Epidemiological studies have shown that 70-90% of all cancers are related to the environmental behavioral factors and may have implications for cancer prevention. Two genes identified through the genome application framework, and well published in the literature, are methylenetetra-hydrofolate reductase (NAD(P)H) (MTHFR) and UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1). Previous meta-analyses on this topic published 2-3 years ago were based on less than or about 1,000 cases, more focused on identifying the CRC genes. Since then, at least 30 times more cases with controls have been published in the literature, further identifying the potential risk factors for the application of cancer genome and CRC prevention.

Procedure: On-line literature were searched from PubMed (PM), PM Central, PM Health databases for systematic reviews and meta-analyses by using a variety of combinations of key words about CRC genes, cancer prevention, human models, and clinical trials. For this analysis, 51 studies that have been published within the last 10 years, published with data containing both control and CRC cases of human samples were identified. These papers were then evaluated with the criteria for the quality of studies. With exclusion of repeated data, 50 studies were included, 46 and 4 studies focused on MTHFR and UGT1A1 respectively.

Summary of Data Findings: Preliminary analyses included 31,674 CRC cases and 30,543 controls associating the MTHFR with CRC in 46 studies; and 938 cases and 866 controls associating UGT1A1 gene with CRC in 4 studies. Risk factors identifying the potential benefits of folate and vitamin B's and C are included in the 35 studies that have associated MTHFR with CRC. These studies included samples of all races and many ethnicity groups, and both genders. They have been published across various continents worldwide. While there are inconsistent findings for the association of these genes with CRC, two major single nucleotide polymorphisms (SNPs) for the MTHFR associated with CRC are MTHFR C677T (rs 1801133) and MTHFR A1298C (rs 1801131). The SNP variants in MTHFR have been associated with the prognosis and treatment efficacies of CRC. For prevention, enzyme pathways for folate and vitamin B's or C intake and metabolic mechanisms have been associated with the prognosis and treatment effects of CRC. While folate and associated vitamins have benefits, alcohol intake increases the risks of CRC. Additionally, while a fiber rich diet including cruciferous vegetables and polyphenols from fruits may be beneficial for CRC prevention, smoking may increase the risk and worsen the prognosis.

Conclusion: Following analysis of these studies, it can be recommended that primary prevention of CRC could include having a diet rich in fiber, high in folate and vitamin B's and C content, and avoid smoking and heavy alcohol use. Meta-analysis of these studies has important impact for health habits and screening. The most common risks for CRC are preventable with life style changes, such as taking nutritional diet and creating healthy behaviors to help the human epigenetic in-vivo environment free from cancers.

Citation Format: Amanda Lie, S. Pamela Shiao, Melissa J. LaBonte, Ching-Yi Chiu, Linda H. Chiang, Rose Sakamoto. Meta-analyses of MTHFR and UGT1A1 genes as risk factors for colorectal cancer prevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B01.