BRCA mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees

摘要

Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mutation rate in families with Pr C associated with breast and/or ovarian cancers;secondary aims were to compare the characteristics of families and BRCA-related Pr C outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test,we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score≥7 Pr Cs,by testing breast or ovarian cases and inferring the mutation in the prostate cases.The characteristics of families and BRCA-related Pr C outcomes were measured using the chi-square(χ^(2))test and Kaplan–Meier methods,respectively.Results:Among 6,591 families,580(8.8%)with a Gleason score≥7 Pr Cs were identified,of which 332(57.2%)met the Modena selection criteria for BRCA testing.Overall,215 breast or ovarian cancer probands(64.8%)were tested,of which 41 resulted positive for BRCA and one for CHEK2 genes(19.5%).No statistically significant differences were found in BRCA-related Pr C prognosis and in the characteristics of families among BRCA1,BRCA2 and non-tested patients.Ten of 23(44%)mutations in the BRCA2 gene fell in the prostate cancer cluster region(PCCR)at the 3′terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and Pr C.A trend toward a worse prognosis has been found in BRCA2 carriers.