Other cancer types besides breast and ovarian cancer in 266 families with a proven BRCA1/2 mutation or a high probability for an autosomal dominant gene

Abstract

Objective: BRCA1/2 mutations go along with a significantly elevated lifetime risk for breast and ovarian cancer reaching up to 80% and 50% respectively. Both genes are supposed to participate in a common pathway that is involved in the control of DNA damage repair. This fundamental role rises the question whether mutations in these genes predispose towards cancerous lesions in other tissues. Patients: Our data were collected in a prospective study of women participating in a screening programme supported by the German Cancer Aid. We report on 2982 family members of 266 high risk families for breast and ovarian cancer. 452 probands were tested positive for a mutation in the BRCA1/2 gene, 329 carried an unclassified variant and 550 had no identified mutation although they had a strong familial background. The remaining 1651 probands are first-degree relatives of those genetically characterised patients. Later ones had a 50% risk of carrying a mutation in a high risk gene. Results: We evaluated the associated tumors and their frequencies in the different genetically determined subgroups. The cancer entities most often reported were bowl cancer (57), lung cancer (34), leukemia and lymphomas (23), melanoma (18), prostate cancer (16) and pancreatic cancer (14) in decreasing frequencies. In the group without a BRCA1/2 mutation cancers of the gastrointestinal tract occurred most often. There were more skin cancers in BRCA1 carriers compared to any other group whereas there was a preponderance of prostate cancer in BRCA2 mutation carriers. Discussion: Overall, associated tumors are relatively infrequent in breast and ovarian cancer families. BRCA1, BRCA2 and BRCA1/2 negative risk families exhibit different associated tumor entities. This fact may contribute to phenotyping of these families. Still, additional cancer risks may be worthwhile considering when setting up preventive care in these families.