Higher genetically predicted low‐density lipoprotein levels increase the renal cancer risk independent of triglycerides and high‐density lipoprotein levels: A Mendelian randomization study

Abstract The causation between lipids and renal cancer remains inconclusive. Our purpose is to explore the causal relationships between the three primary lipid metabolism‐related substances, namely triglycerides (TG), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) with the risk of renal cancer using Mendelian randomization (MR) methods. Genetic instruments for lipids were acquired from the UK Biobank. Outcome data were from the FinnGen study (1397 renal cancer cases and 204 070). Single‐variable MR (SVMR) and multi‐variable MR (MVMR) analyses were conducted with TwoSampleMR package based on R 4.0.3. The random‐effect inverse‐variance weighted (IVW), MR‐Egger, weighted‐median method, and weighted mode were the four main computing methods. We found that per 1 SD elevated LDL level was causally associated with renal cancer occurrence based on SVMR (OR, 1.31, 95% CI: 1.05‐1.64, P = .016). Similar significant associations were found in other methods. However, the results of SVMR did not support significant associations between TG, and HDL with renal cancer risk in all methods. The association between LDL and renal cancer was still significant in MVMR analysis (OR for IVW method: 1.22 per 1 SD higher trait (SD, 95% CI: 1.11‐1.34, P < .001; OR for MR‐Egger: 1.22 per 1 SD higher trait, 95% CI: 1.01‐1.47, P = .042) when taking TG and HDL into consideration. Our study supported that elevated serum LDL levels is causally associated with an increased risk of renal cancer independent of TG and HDL.