Two-sample mendelian randomization reveals a causal association between membranous nephropathy and lung cancer

Abstract

A risk association between membranous nephropathy (MN) and lung cancer is reported, but traditional observational studies cannot provide strong evidence of its causality. This study aimed to assess genome-wide association studies data for a causal relationship between MN and lung cancer using a two-sample Mendelian randomization (MR) approach. Inverse-variance weighted, and MR Egger regression techniques were used to determine the association of genetic variants from cohorts of MN and lung cancer patients. Independent genetic variants with genome-wide significance (P < 5×10–8) were used to determine the direction of chance. Sensitivity analyses confirmed the accuracy of the results. The results suggest that MN is an exposure factor for lung cancer, validated using a second cohort of lung cancer patients (P < 0.001). There is insufficient evidence to suggest a causal relationship between lung cancer and MN; however, cigarette smoking may be a confounding factor for lung cancer due to MN. The findings provide causal evidence for the effect of MN on lung cancer risk and may be useful for patient management, especially in older patients with MN who should be systematically screened regularly.

Identification and validation of biomarkers in membranous nephropathy and pan-cancer analysis

“…Although a causal association between lung cancer and MN was not found in the Mendelian randomization-based study by Yang et al. ( 44 ), we don’t think they are the opposite of our conclusions. We speculate that the negative result may be related to the fact that the investigators used the primary MN dataset for their analyses.…”