Abstract
BACKGROUND: Observational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method. METHODS: With a two-sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer. RESULTS: Our results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01-fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34-3.01; P = 7.40 × 10(-4) ). Additionally, lung cancer was not a causal factor for DPA. The results of MR-Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy. CONCLUSIONS: Genetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.