Gastrointestinal cancer risk in Irish hereditary breast ovarian cancer families.

Abstract

e12565 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 gastrointestinal malignancies in BRCA1 or 2 mutation carriers. Two large studies in Ashkenazi Jewish populations subsequently contradicted this evidence, although only the three founder mutations were included in these studies. We report the Irish experience of colorectal and gastro-oesophageal (GE) cancer in Irish hereditary breast ovarian cancer (HBOC) families. Methods: 104 HBOC families at two tertiary referral centres were reviewed for the presence of early onset gastrointestinal (GI) malignancies. The medical records of individuals with GI cancer were reviewed to determine carrier status. Clinical data including age at 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 33 individuals with GI malignancies in 102 HBOC families (22 with colorectal, 11 with gastric). Definitive carrier status was available on 8 individuals. An additional 7 individuals were obligate carriers. Age at diagnosis ranged from 27-84 years (median=60). Median age of colorectal cancer diagnosis among carriers was 54 compared with 61 among non-carriers. Median age of gastric cancer 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 60 Irish HBOC families are being screened for GI malignancies and updated data will be presented at the meeting.