G84E mutation in HOXB13 is firmly associated with prostate cancer risk: a meta-analysis

Abstract

The rare but recurrent germline G84E mutation in HOXB13 was recently found to be associated with a significantly increased risk of familial prostate cancer (PCa). However, epidemiologic findings have been inconsistent. In an attempt to confirm and expand the findings that the PCa risk increased in men carrying G84E, we therefore performed a meta-analysis to clarify the association between the germline G84E mutation and PCa risk. We also aim to verify the increased PCa risk with respect to diagnostic age, family history, and disease aggressiveness. Comprehensive search of databases was carried out, and other relevant articles were also identified. Then, the meta-analyses were conducted according to the standard guidelines. A total of 11 studies with 120,167 participants were included on the basis of inclusion criteria. The G84E allele carrier frequencies ranged from 0.1 to 4.9 % in the patients with PCa, as compared with 0 to 1.4 % in control subjects. Men with the HOXB13 G84E variant had a 4.51-fold higher relative risk of PCa compared with non-carriers (95 % CI 3.28-6.20). The much higher risks were observed in individuals with early onset (odds ratio (OR) = 9.73, 95 % confidence interval (CI) 6.57-14.39), more than two affected relatives (OR = 7.27, 95 % CI 4.02-13.15), and highly aggressive disease (OR = 5.81, 95 % CI 3.72-9.08). Our findings provide further evidences that the rare mutation in HOXB13 contributes to both hereditary and sporadic PCa risk. Despite the low G84E carrier rate, biological and clinical implications of the mutation in subjects with early onset, more than two affected relatives, and highly aggressive disease remain important in continued investigation.