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.
| Authors | Seviiri, Mathias; Law, Matthew H; Ong, Jue-Sheng; Gharahkhani, Puya; Nyholt, Dale R; Olsen, Catherine M; Whiteman, David C; MacGregor, Stuart |
|---|---|
| Journal | Cancer Epidemiology Biomarkers and Prevention |
| Pages | 1591-1598 |
| Volume | 30 |
| Date | 1/01/2021 |
| Grant ID | |
| Funding Body | |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/1055-9965.EPI-20-1765 |