Abstract
Background/Objective:
Folates are essential for DNA synthesis and methylation, and thus may have a role in carcinogenesis. Limited evidence suggests folate-containing foods might protect against some cancers and may partially mitigate the increased risk of breast cancer associated with alcohol intake, but there is little information regarding ovarian cancer. Our aim was to evaluate the role of folate and related micronutrients, polymorphisms in key folate-metabolising genes and environmental factors in ovarian carcinogenesis.
Subjects/Methods:
Participants in the Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires. DNA samples (1638 cases, 1278 controls) were genotyped for 49 tag single-nucleotide polymorphisms (SNPs) in the methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) genes. Logistic regression models were used to generate adjusted odds ratios and 95% confidence intervals.
Results:
We saw no overall association between the intake of folate, B vitamins or other methyl donors and ovarian cancer risk, although increasing folate from foods was associated with reduced risk among current smokers (Ptrend=0.03) and folic acid intake was associated with borderline significant increased risks among women who consumed ⩾1 standard alcoholic drinks/day (odds ratio (OR)=1.64; 95% confidence interval (CI) 1.05–2.54, Ptrend=0.05). Two SNPs (rs7365052, rs7526063) showed borderline significant inverse associations with ovarian cancer risk; both had very low minor allele frequencies. There was little evidence for interaction between genotype and micronutrient intake or for variation between different histological subtypes of ovarian cancer.
Conclusions:
Our data provide little evidence to support a protective role for folate in ovarian carcinogenesis but suggest further evaluation of the joint effects of folic acid and alcohol is warranted.
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Acknowledgements
We acknowledge the cooperation of the following institutions: New South Wales: John Hunter Hospital, North Shore Private Hospital, Royal Hospital for Women, Royal North Shore Hospital, Royal Prince Alfred Hospital, Westmead Hospital, New South Wales Cancer Registry; Queensland: Mater Misericordiae Hospital, Royal Brisbane and Women's Hospital, Townsville Hospital, Wesley Hospital, Queensland Cancer Registry; South Australia: Flinders Medical Centre, Queen Elizabeth II, Royal Adelaide Hospital, South Australian Cancer Registry; Tasmania: Royal Hobart Hospital; Victoria: Freemasons Hospital, Mercy Hospital For Women, Monash Medical Centre, Royal Women's Hospital, Victorian Cancer Registry; and Western Australia: King Edward Memorial Hospital, St John of God Hospitals Subiaco, Sir Charles Gairdner Hospital, Western Australia Research Tissue Network, Western Australia Cancer Registry. We also acknowledge the contribution of the study nurses and research assistants, and we would like to thank all of the women who participated in the study. These analyses were funded by the Queensland Cancer Council (389880). The Australian Ovarian Cancer Study was supported by the US Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and the Cancer Foundation of Western Australia; the Australian Cancer Study was supported by the National Health and Medical Research Council (NHMRC) of Australia (199600). PM Webb and G Chenevix-Trench are supported by Fellowships from the NHMRC.
Full membership of the Australian Ovarian Cancer Study Group is listed at http://www.aocstudy.org/; the Australian Cancer Study Investigators are A Green, P Parsons, N Hayward, P Webb and D Whiteman.
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Webb, P., Ibiebele, T., Hughes, M. et al. Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer. Eur J Clin Nutr 65, 1133–1140 (2011). https://doi.org/10.1038/ejcn.2011.99
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DOI: https://doi.org/10.1038/ejcn.2011.99
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