HOXB13 Mutation and Prostate Cancer: Studies of Siblings and Agressive Disease
A partir des données de deux cohortes incluant un total de 2 665 participants américains d'origine européenne, cette étude analyse l'association entre une mutation du gène HOXB13 et le risque de cancer de la prostate
Background: Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans. Methods: We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N=2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans. Results: In our studies the mutation was found exclusively among men with prostate cancer (carrier frequency=1.48%) or unaffected brothers of cases carrying the mutation (frequency=0.34%), and carrying the mutation gave an odds ratio for disease=4.79 (P=0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P=3.5x10-17), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P<1x10-5. Conclusions: The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men. Impact: Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer.