Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation analysis

Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk, putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomized controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma. To perform MR, we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark large predicted change in PUFAs in which, for example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17(th) percentile to the median. Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only negligibly changed melanoma risk: odds ratio [OR]=1.03 (95% confidence interval [CI]=0.96-1.10). Other PUFAs yielded similar results as DPA. Our MR analysis suggests that the effect of PUFA levels on melanoma risk is either zero or very small. What's new? Studies have indicated that dietary interventions might be able to reduce melanoma risk. The Mediterranean diet, which includes ample intake of polyunsaturated fatty acids (PUFAs), has shown particular promise. In this statistical analysis, the authors used a technique called Mendelian randomisation, in which certain SNPs are associated with a particular variable e.g. PUFA, to assess whether PUFA levels affect melanoma risk. Their results indicate that the impact of dietary PUFAs is negligible. Further studies are thus needed to explore whether other components of the Mediterranean diet might reduce melanoma risk.