Polyunsaturated fatty acid levels and the risk of keratinocyte cancer: A Mendelian Randomisation analysis
Menée à l'aide d'une méthode de randomisation mendélienne et de données portant au total sur plus d'1,2 million de participants, cette étude analyse l'association entre les niveaux estimés d'acides gras poly-insaturés et le risque de tumeurs d'origine kératinocytaire
Background: Keratinocyte cancer (KC) is the commonest cancer, imposing a high economic burden on the healthcare system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFAs) and KC; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We explored if genetically predicted PUFA levels are associated with BCC and SCC risks. Methods: We conducted a two sample Mendelian Randomisation study using PUFA level GWASs from the CHARGE consortium (n > 8,000), and the meta-analysis GWASs from UKB, 23andMe and Qskin for BCC (n=651,138) and SCC (n= 635,331) risk. Results: One standard deviation increase in genetically predicted levels of linoleic acid (OR = 0.94, 95% CI = 0.91-0.97, P = 1.4 × 10-4) and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10-4) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10-4) and eicosapentaenoic acid (OR=1.10, 95% CI = 1.04-1.16, P = 1.5 × 10-3) were associated with an increased BCC risk. Conclusion: Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk. Impact: PUFA related diet and supplementation could influence BCC aetiology.