Abstract
With increasing life spans, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC), which can considerably shorten survival. Lung cancer (LC) is a common SPC among BC survivors. This study explored the association between these two cancers through Mendelian randomization (MR) analysis. A bidirectional two-sample MR analysis was conducted with BC genome-wide association study (GWAS) data from the Breast Cancer Association Consortium (BCAC) included 228,951 individuals and the GWAS summary statistics from the Transdisciplinary Research in Cancer of the Lung (TRICL) of LC included 112,781 individuals. The IVW method and MR-RAPS method showed a causal effect of overall BC on lung adenocarcinoma (LUAD) (IVW: OR = 1.060, 95% CI = 1.008-1.116, P = 0.024; MR-RAPS: OR = 1.059, 95% CI = 1.005-1.116, P = 0.033), which indicated that patients with BC had an increased risk of LUAD. However, there is no strong evidence for a causal effect of LUAD on BC. Our study revealed a causal effect of BC on second primary LUAD, suggesting that we should intensify screening for second primary LC in BC survivors. Early intervention and treatment for patients with second primary LC are needed to reduce mortality in BC survivors.