Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants

This study assessed the prevalence, age and gender distribution of PDAC/BTC cases in families known to carry aBRCA1/2 PV compared to those of the Irish population. A review of all families referred to a national genetics clinic from 09/11/1997 to 01/06/2018 was performed. The BOADICEA algorithm was used to estimate the probability that an untested relative of a knownBRCA1/2 PV carrier with PDAC was a carrier. We reviewed 3252 family pedigrees, 1193 contained a proband who underwent testing forBRCA1/2 based on Manchester score  ≥ 15. Among 128BRCA2 PV-positive families, 27 (21%) contained a 1st/2nd/3rd-degree relative with PDAC, while of 116BRCA1 PV-positive families, 11 (9%) contained a 1st/2nd/3rd-degree relative with PDAC. Within these 38 families, 25 patients with PDAC had  ≥ 50% likelihood of being aBRCA1/2 PV carrier. This cohort had a median age at diagnosis of 55  years (range 33–75), with a mean (55 years) lower than 8364 patients with PDAC identified through the National Cancer Registry of Ireland (71 years, p <  0.0001). SixBRCA2 positive (5%) and 2BRCA1 positive pedigrees (2%) included an individual with BTC; median age at diagnosis was 65  years (range 33–99). PDAC and BTC are prevalent in Irish families harbouring aBRCA2 PV and are associated with early-onset malignancy. This supports current guidelines recommending universal germline testing for PDAC patients.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research