![]() Mendelian randomisation is based on the principle of random assortment of alleles at conception, and may identify causal risk factors for disease by utilising a number of genetic variants (also known as the genetic instrument) as a proxy for an exposure. Given these potential limitations of observational studies the estimation of an unbiased (potentially causal) association may be difficult. As a result, reverse causation in studies of prostate cancer and diet (regardless of whether diet was measured via food frequency questionnaire or biomarkers) may be of particular concern, given the slow growth of most prostate tumours and the prospect that men diagnosed with low risk (i.e., low volume and grade) disease may not be treated for several years in accord with current treatment guidelines. Although biomarker PUFA measurements may provide an objective measure of intake, depending on the biomarker used (i.e., serum vs red blood cell) the time period of exposure will vary ( Arab, 2003), and thus an objective PUFA measurement may not represent the relevant aetiologic time period. Measurement error is an important limitation for studies examining diet via food frequency questionnaires. Observational studies of dietary factors and cancer risk are prone to biases, including confounding, selection bias, measurement error, and reverse causation. However, the association between PUFAs and prostate cancer risk is not supported by a recent meta-analysis summarising prospective studies of long-chain ω-3 PUFA intake and prostate cancer incidence that reported null results for both self-reported dietary intakes and biomarker measures of PUFAs ( Alexander et al, 2015). On the contrary, products of ω-3 PUFA metabolism via these same biologic pathways have demonstrated anti-inflammatory properties ( Chapkin et al, 2009). Others include the lipoxygenase and cytochrome p450 pathways producing leukotrienes and hydroxyeicosatetraenoic acids, which have also been implicated in cancer development ( Panigrahy et al, 2010 Wang and Dubois, 2010). Specifically, metabolism of ω-6 PUFAs via the cyclooxygenase-2 enzyme results in the production of inflammatory mediators including prostaglandin E2 that has been reported to affect prostate carcinogenesis ( Sobolewski et al, 2010). Given the possible role that PUFAs may have in prostate carcinogenesis, with suggested anti-inflammatory effects for ω-3 PUFAs and inflammatory effects for ω-6 PUFAs ( Berquin et al, 2011), an examination of these nutritional factors may be warranted. ![]() Several previous epidemiologic studies have examined the relation between polyunsaturated fatty acids (PUFAs) and prostate cancer risk ( Zock and Katan, 1998 Carayol et al, 2010 Sakai et al, 2012 Alexander et al, 2015). However, little is known about modifiable factors for this common cancer. ![]() Identifying modifiable prostate cancer risk factors could help to alleviate the burden of prostate cancer. Prostate cancer is the most common cancer among Caucasian men worldwide ( Torre et al, 2015). Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer. However, risk reductions were observed for short-chain PUFAs, linoleic (OR LA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (OR ALA=0.96, 95%CI=0.93, 0.98), among men <62 years whereas increased risk was found among men ⩾62 years for LA (OR LA=1.04, 95%CI=1.01, 1.07). No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression. We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortiumīritish Journal of Cancer volume 115, pages 624–631 ( 2016) Cite this article
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