title: MGMT Ile143Val polymorphism, dietary factors and the risk of breast, colorectal and prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study.
abstract: O(6)-Methylguanine-DNA methyltransferase (MGMT) repairs DNA damage caused by alkylating agents including N-nitroso compounds from diet. MGMT Ile143Val polymorphism may lead to less DNA damage repair and increased cancer risk depending on the environmental exposures. We investigated interactions between dietary factors and the MGMT Ile143Val polymorphism in relation to breast, colorectal and prostate cancer risk. There were 276/1498, 273/2984 and 312/1486 cases/controls for the breast, colorectal and prostate cancer studies respectively; all nested within the EPIC-Norfolk study, a prospective cohort of approximately 25,000 men and women aged 40-79. Baseline 7-day food diary data were collected for dietary assessment. MGMT Ile143Val polymorphism was not overall associated with breast, colorectal and prostate cancer risk. There was a significant interaction between this polymorphism and intake of red and processed meat on colorectal cancer risk (P(interaction)=0.04) suggesting an increased risk among carriers of the variant genotype compared to the MGMT Ile143Ile common genotype. A lower colorectal cancer risk was seen with higher intake of vitamin E and carotene among the variant genotype group but not in the common genotype group (P(interaction)=0.009 and P(interaction)=0.005 for vitamin E and carotene, respectively). A higher prostate cancer risk was seen with higher alcohol intake among the variant genotype (OR=2.08, 95% CI=1.21-3.57, P(interaction)=0.0009) compared to the common genotype with lower alcohol intake. In this UK population, the MGMT Ile143Val polymorphism was not overall associated with breast, colorectal and prostate cancer risk. There was evidence for this polymorphism playing a role in modulating the risk of prostate cancer in presence of alcohol. For colorectal cancer, the MGMT Ile143Val polymorphism may confer increased or decreased risk depending on the dietary exposure.
authors.affiliation: MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, United Kingdom. yet@srl.cam.ac.uk
authors.forename: Yet Hua
authors.initials: YH
authors.lastname: Loh
authors.forename: Panagiota N
authors.initials: PN
authors.lastname: Mitrou
authors.forename: Richard
authors.initials: R
authors.lastname: Bowman
authors.forename: Angela
authors.initials: A
authors.lastname: Wood
authors.forename: Hannah
authors.initials: H
authors.lastname: Jeffery
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.forename: Marleen A H
authors.initials: MA
authors.lastname: Lentjes
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Rodwell
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D005260:Female; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D014633:Valine / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D007532:Isoleucine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D014633:Valine