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

Area of Science:

• Genetics
• Epidemiology
• Oncology

Background:

• Previous studies on pernicious anemia (PA) and cancer risk, excluding gastric cancer, yielded contradictory results.
• Investigating the potential causal links between PA and various cancers is crucial for understanding disease etiology.

Purpose of the Study:

• To examine the potential causal relationship between pernicious anemia and 20 site-specific cancers using a bidirectional two-sample Mendelian randomization analysis.

Main Methods:

• Utilized genetic summary data from the European FinnGen project for PA and 20 cancers.
• Employed the inverse variance weighting (IVW) method for causal inference, with Benjamini-Hochberg correction for multiple testing.

Main Results:

• Identified a causal relationship between PA and gastric, prostate, testicular cancers, and malignant melanoma of the skin.
• Confirmed causal links between PA and gastric/prostate cancers, and reverse causal links with gastric cancer, post-correction.
• MR-Egger and MR-PRESSO tests indicated no significant horizontal pleiotropy.

Conclusions:

• Pernicious anemia demonstrates a potential genetic association with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of the skin.