Causal relationship between prostate cancer and 12 types of cancers: multivariable and bidirectional Mendelian randomization analyses.

Abstract

Previous observational studies have shown an association between certain cancers and the subsequent risk of prostate cancer (PCa). However, the causal relationship between these cancers and PCa is still unclear. This study aimed to investigate the causal relationship between 12 common cancers and the risk of PCa. We employed genome-wide association studies (GWAS) to perform forward and reverse Mendelian randomization (MR) within two-sample frameworks. Furthermore, we conducted multivariable MR analyses to investigate the relationships between different types of cancer. In addition, multiple sensitivity analysis methods were employed to assess the robustness of our findings. Our univariable MR analysis showed that genetically predicted hematological cancer was associated with a reduced risk of PCa (OR: 0.911, 95% CI 0.89-0.922, P = 0.03). Furthermore, MR analysis demonstrates that genetically predicted occurrence of thyroid gland and endocrine gland cancer also raised the risk of PCa (all P < 0.05). Multivariable analysis showed that thyroid gland cancer exhibited a higher incidence of PCa (OR: 1.12, 95% CI: 1.08-1.16, P = 0.008). In the reverse MR analysis, we found no significant inverse causal associations between PCa and 12 types of cancers. In summary, this study provided insights into the causal relationships between various types of cancer and PCa. Hematological cancer was suggested to associate with a lower risk of PCa, while thyroid gland cancer and endocrine gland cancer might increase the risk. These findings contribute to the understanding of genetic factors related to PCa and its potential associations with other cancers.