Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: Influence on prostate cancer risk and interactions, "Beyond the Abstract," by Lindsay Kobayashi and Kristan J. Aronson, PhD

BERKELEY, CA (UroToday.com) - This study examined three possible factors that could increase risk of prostate cancer: folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism. We postulated that these risk factors interact with one another in causing prostate cancer, rather than working individually, and we undertook this study to help understand how folate intake, alcohol consumption, and MTHFR C677T may work together to contribute to prostate cancer etiology.

Folate is a water-soluble B vitamin available in many foods and supplements that is essential for many functions, including DNA methylation.[1] Folate has a potentially complex role in prostate cancer, where low levels may contribute to initial carcinogenesis, but low levels may also be protective against progression of existing tumours.[2, 3, 4, 5, 6] We considered alcohol consumption jointly with folate intake, as alcohol directly interferes with folate absorption.[7] For example, heavier drinkers have a greater need for folate, and those with low folate intake may have an even higher risk for prostate cancer. This is called an “interaction” between folate intake and alcohol consumption, and this interaction has rarely been considered in previous studies.[3, 4, 8, 9] A third factor that may interact with both folate intake and alcohol consumption in prostate cancer risk is genetic: the C677T polymorphism of the MTHFR gene. This gene encodes the MTHFR enzyme, playing an essential role in folate metabolism [10]. The effects of this polymorphism on prostate cancer etiology may depend on the amount of folate in the diet and/or the amount of alcohol regularly consumed,[10, 11, 12, 13] so our study objective was to assess the independent and joint impacts of folate intake, alcohol consumption, and the MTHFR C677T polymorphism on prostate cancer risk.

Our study at Kingston General Hospital in Kingston, Ontario, Canada from 1997-1999 included 80 prostate cancer cases and 334 comparable men (controls) without cancer aged 50-80 years old. We estimated folate intake and alcohol consumption in the time two years prior to completing a self-administered questionnaire, and approximately half of all cases and controls provided a blood sample for MTHFR genotyping. Our main finding was that consumption of more than five alcohol drinks per week was associated with increased prostate cancer risk of over two-fold among men with low folate intake (OR: 2.38; 95% CI: 1.01-5.57) and of over four-fold among the sub-group of men with the wildtype (CC) MTHFR genotype (OR: 4.43; 95% CI: 1.15-17.05).

The case-control design we employed is the most common and efficient way to study causes of prostate cancer in humans. However, case-control studies of prostate cancer are not without limitation as well – one major challenge of prostate cancer case-control studies is finding cancer-free controls that accurately represent the general population from which the cases arose. Because of the slow-growing nature of prostate cancer, control groups are often contaminated with men who already have prostate cancer (this is called “latent” which means not yet diagnosed, but existing prostate cancer), which can make research results invalid. In our study, we excluded men who did not have normal age-specific prostate specific antigen levels or a normal digital rectal examination, or who had a diagnosis of prostatic intraepithelial neoplasia or were using a hormonal medication: in this way, our study is stronger than those that have not excluded latent prostate cancer cases. Another strength is that participants completed the study questionnaire prior to knowledge of their prostate cancer diagnosis: this means that our results are not biased by only cases remembering possible exposures that could have caused their cancer. Together, these design aspects make our study findings high quality in terms of internal validity of results. However, the major limitation of this research is the small sample size of our study, and therefore more studies are needed to draw firm conclusions. Our findings of increased prostate cancer risk with the wildtype MTHFR genotype, combined with higher alcohol consumption, indicate that this interaction needs to be considered in future studies. Similarly, while there was no risk associated with folate alone, the combination of low folate intake and high alcohol consumption indicates an interaction that needs to be investigated in future studies.

Our results highlight the complex relationships between folate, alcohol, and genetic factors as possible causes of prostate cancer. Studies like ours provide initial indications of potentially important gene-environment and environment-environment interactions that deserve further investigation. In particular, given current mandatory policies of dietary folate fortification in many countries and the prevalence of heavy alcohol consumption, these factors deserve attention in further research and prevention programs.

References:

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Written by:
Lindsay Kobayashi and Kristan J Aronson, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Department of Community Health and Epidemiology, Queen's University, Kingston, ON, Canada
Division of Cancer Care and Epidemiology, Queen's Cancer Research Institute, Queen's University, Kingston, ON, Canada

Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: Influence on prostate cancer risk and interactions - Abstract

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