Familial cancer risks to offspring from mothers with 2 primary breast cancers: leads to cancer syndromes.

The nationwide Swedish Family-Cancer Database was used to analyse the risk of cancer among the offspring of bilateral breast cancer patients. We studied 4,734 such mothers who had 9,391 offspring, of whom 328 presented with a primary cancer in the years 1958-1996. Standardised incidence ratios (SIRs) were increased for breast [SIR 3.05, 95% confidence interval (CI) 2.57-3.59], ovarian (SIR 1.84, 95% CI 1.03-3.05) and anogenital (SIR 1.75, 95% CI 1.11-2.63) cancers and childhood sarcomas (SIR 9.39, 95% CI 1.93-29.13). Additionally, squamous-cell skin cancer was increased among sons and all childhood cancers among daughters. When analysed by histological type, adenocarcinomas of the breast and ovary, all squamous-cell carcinomas and tumours at glandular epithelium (seminomas and intestinal carcinoids) were increased. Mothers with bilateral breast cancer had an excess of 2 or more children with cancer. The increased risk of ovarian cancer is consistent with germline mutations in the BRCA1 and BRCA2 genes, while the risk of soft tissue and bone sarcomas may reflect the association of these tumours with Li-Fraumeni syndrome. The increases in squamous-cell carcinomas at many sites may reflect a new susceptibility syndrome.