B39
No association between MGMT codon 143 polymorphism and risk of breast, colorectal and prostate cancers in EPIC-Norfolk Study
Yet hua Loh1, Richard Bowman2, Panagiota Mitrou3, Angela Wood4, Robert N Luben4, Kay-Tee Khaw4, Sheila A Bingham1
1MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, University of Cambridge, Cambridge, Cambridgeshire, UK, 2MRC Dunn Human Nutrition Unit, Cambride, Cambridgeshire, UK, 3World Cancer Research Fund International, London, UK, 4Department of Public Health and Primary Care, University of Cambridge, Cambridge, Cambridgeshire, UK
Background
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is involved in the cellular defence against DNA alkylation damage. Red and processed meat are sources of N-nitroso compounds in the large intestine. Most N-nitroso compounds are alkylating agents. MGMT Ile143Val (rs 2308321) polymorphism may lead to less DNA damage repair and increased cancer risk when more N-nitroso compounds are available with increased red/processed meat intake. To our knowledge, no study has investigated the interactive effects between MGMT Ile143Val polymorphism and red/processed meat intake on breast, colorectal and prostate cancer risk.
Aims
Our primary aim was to investigate if MGMT codon 143 gene polymorphism is associated with breast, colorectal and prostate cancer risk. We also assessed the potential interaction between this polymorphism and red/processed meat intake on the risk of these cancers.
Method
We conducted matched case-control studies nested within the EPIC-Norfolk Study, a prospective cohort of ~25,000 men and women aged 40-79. Health and lifestyle questionnaire and 7-day food diary data were collected at baseline. Pyrosequencing was used to determine the MGMT Ile143Val genotype. There were 246 breast, 244 colorectal and 263 prostate cancers for analyses.
Results
MGMT Ile143Val polymorphism was not overall associated with breast, colorectal and prostate cancer risk. We found no evidence for an interaction between red/processed meat and genotype on the risk of these cancers.
Conclusion
These findings suggest that MGMT Ile143Val polymorphism does not have a major effect on breast, colorectal and prostate cancer risk and there was no effect modification by red or processed meat intake.
