Family History of Breast Cancer Is Associated with Elevated Risk of Prostate Cancer: Evidence for Shared Genetic Risks

Introduction: Although breast and prostate cancers arise in different organs and are more frequent in the opposite sex, multiple studies have reported an association between their family history. Analysis of single nucleotide polymorphism data, based on distant relatives, has revealed a small positive genetic correlation between these cancers explained by common variants. The estimate of genetic correlation based on close relatives reveals the extent to which shared genetic risks are explained by both common and rare variants. This estimate is unknown for breast and prostate cancer. Method: We estimated the relative risks, heritability, and genetic correlation of breast cancer and prostate cancer based on the Minnesota Breast and Prostate Cancer Study, a family study of 141 families ascertained for breast cancer. Results: Heritability of breast cancer was 0.34 (95% credible interval: 0.23-0.49) and 0.65 (95% credible interval: 0.36-0.97) for prostate cancer, and the genetic correlation was 0.23. In terms of odds ratios, these values correspond to a 1.3 times higher odds of breast cancer among probands, given that the brother has prostate cancer. Conclusion: This study shows the inherent relation between prostate cancer and breast cancer; an incident of one in a family increases the risk of developing the other. The large difference between estimates of genetic correlation from distant and close relatives, if replicated, suggests that rare variants contribute to the shared genetic risk of breast and prostate cancer. However, the difference could stem from genotype-by-family effects shared between the two types of cancers.