Gastrointestinal cancer risk in Irish hereditary breast ovarian cancer families.

Abstract

413 Background: Colorectal and breast cancer are linked in certain predisposition syndromes such as Cowden and Peutz-Jegers syndrome. Breast cancer risk also appears increased in certain Lynch syndrome kindreds. Original reports suggested an increased risk of colorectal malignancies in BRCA1/2 mutation carriers. Two large studies in Ashkenazi Jewish populations subsequently contradicted this early evidence, although neither study was powered to address effects if each gene independently, or other modifier effects in certain families. We report the Irish experience of colorectal and gastro-esophageal (GE) cancer in hereditary breast ovarian cancer (HBOC) families. Methods: 97 HBOC families at two tertiary referral centres were reviewed for the presence of early onset GE malignancies. The medical records of individuals with GE cancer were reviewed to determine carrier status. Clinical data including age of diagnosis, stage, treatment and outcome were extracted. Median age of diagnosis and outcome were compared among BRCA1/2 mutation carriers and non-carriers. Results: We identified 30 individuals with GE malignancies in 97 HBOC families (19 with colorectal, 11 with gastric). Two families were excluded as Lynch syndrome was also diagnosed in these families. Definitive carrier status was available on 8 individuals. Additional 7 individuals were obligate carriers. Age at diagnosis ranged from 27-84 years (median=60). Median age of CRC diagnosis among carriers was 54 compared with 61 among non-carriers (p=0.20). Median age of gastric diagnosis among carriers was 66 compared with 53 among non-carriers. Conclusions: Early onset colorectal cancer occurs in certain HBOC families and may be related to mutation status. No genotype-phenotype association was identified in this study. An additional 150 Irish HBOC families are being screened for early onset GI malignancies and updated data will be presented at the meeting.