While several observational studies have highlighted an inverse relationship between cancer and Alzheimer’s disease, it is not clear whether the observed interrelation between these two disorders is an artifact of study design, uncontrolled confounding, and/or mortality selection. This study uses a statistical genetic approach, which avoids issues of confounding and reverse-causality, to determine the nature of the observed association between cancer and Alzheimer’s disease. 

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 Alzheimer’s disease, 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 Alzheimer’s disease (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 Alzheimer’s disease than non-smoking related cancers (5.2% lower odds, OR 0.95, 95% CI 0.92-0.98, p=0.0026, vs. 1.9% lower odds, OR 0.98, 95% CI 0.97-0.995, p=0.0091).

Genetically predicted lung cancer, leukemia, breast cancer, and all cancers in aggregate are associated with lower odds of incident Alzheimer’s disease. Furthermore, the risk of Alzheimer’s disease was lower in smoking-related versus non-smoking related cancers. These results add to the substantial epidemiological evidence of an inverse association between history of cancer and lower odds of Alzheimer’s disease, by suggesting a causal basis for this relationship.