MLH1 promoter methylation, diet, and lifestyle factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk.

TitleMLH1 promoter methylation, diet, and lifestyle factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk.
Publication TypeJournal Article
Year of Publication2011
AuthorsGay, LJ, Arends, MJ, Mitrou, PN, Bowman, R, Ibrahim, AE, Happerfield, L, Luben, R, McTaggart, A, Ball, RY, Rodwell, SA
JournalNutr Cancer
Volume63
Issue7
Pagination1000-10
Date Published2011
ISSN1532-7914
KeywordsAdaptor Proteins, Signal Transducing, Adult, Aged, Colorectal Neoplasms, Diet, DNA, DNA Methylation, DNA Mismatch Repair, Female, Fruit, Humans, Immunohistochemistry, Life Style, Male, Microsatellite Instability, Middle Aged, MutL Protein Homolog 1, Nuclear Proteins, Promoter Regions, Genetic, Prospective Studies, Smoking, Surveys and Questionnaires, United Kingdom, Vegetables
Abstract

There is conflicting evidence for the role diet and lifestyle play in the development of mismatch repair (MMR)-deficient colorectal cancers (CRC). In this study, associations between MMR deficiency, clinicopathological characteristics, and dietary and lifestyle factors in sporadic CRC were investigated. Tumor samples from 185 individuals in the EPIC-Norfolk study were analyzed for MLH1 gene promoter methylation and microsatellite instability (MSI). Dietary and lifestyle data were collected prospectively using 7-day food diaries (7dd) and questionnaires. MMR-deficient tumor cases (MLH1 promoter methylation positive, MSI-H) were more likely to be female, older at diagnosis, early Dukes' stage (A/B), and proximal in location (MSI-H P = 0.03, 0.03, 0.02, and 0.001, respectively). Tumors with positive MLH1 promoter methylation (>20%) were associated with poor differentiation (P = 0.03). Low physical activity was associated with cases without MSI (P = 0.05). MMR deficiency was not significantly associated with cigarette smoking or alcohol, folate, fruit, vegetable, or meat consumption. We conclude that MMR-deficient tumors represent a distinct subset of sporadic CRC that are proximal in location, early Dukes' stage, and poorly differentiated, in cases that are female and older at diagnosis. There is no overall role for diet and lifestyle in MMR status in CRC, consistent with age-related susceptibility to MLH1 promoter methylation.

DOI10.1080/01635581.2011.596987
Alternate JournalNutr Cancer
Citation Key10.1080/01635581.2011.596987
PubMed ID21875327
Grant ListMC_U105630924 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom