Evidence of a Causal Association Between Cancer and Alzheimer’s Disease: a Mendelian Randomization Analysis

Abstract

While limited observational evidence suggests that cancer survivors have a decreased risk of developing Alzheimer’s disease (AD), and vice versa, it is not clear whether this relationship is causal. Using a Mendelian randomization approach that provides evidence of causality, we found that genetically predicted lung cancer (OR 0.91, 95% CI 0.84–0.99, p = 0.019), leukemia (OR 0.98, 95% CI 0.96–0.995, p = 0.012), and breast cancer (OR 0.94, 95% CI 0.89–0.99, p = 0.028) were associated with 9.0%, 2.4%, and 5.9% lower odds of AD, respectively, per 1-unit higher log odds of cancer. When genetic predictors of all cancers were pooled, cancer was associated with 2.5% lower odds of AD (OR 0.98, 95% CI 0.96–0.988, p = 0.00027) per 1-unit higher log odds of cancer. Finally, genetically predicted smoking-related cancers showed a more robust inverse association with AD than non-smoking related cancers (OR 0.95, 95% CI 0.92–0.98, p = 0.0026, vs. OR 0.98, 95% CI 0.97–0.995, p = 0.0091).