Causal inference between pernicious anemia and cancers: a bidirectional two-sample mendelian randomization analysis

Abstract

Abstract Background Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis. Methods The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. Results Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P 0.05). There was still a reverse causal relationship between gastric cancer and PA (P‘ 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy. Conclusions PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.

Keywords

• Pernicious Anemia
• Vitamin B12 deficiency
• Pan cancer
• Mendelian randomization
• Cancer genetics