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- PMID: 10577927
- UKPMCID: 10577927
- DOI: 10.1086/302671
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The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study.
Stratton, J F; Thompson, D; Bobrow, L; Dalal, N; Gore, M; Bishop, D T; Scott, I; Evans, G; Daly, P; Easton, D F; Ponder, B A
American journal of human genetics. 1999;65(6):1725-32.
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Full-text held externally
- PMID: 10577927
- UKPMCID: 10577927
- DOI: 10.1086/302671
Abstract
We conducted a population-based study to determine the contribution of germline mutations in known candidate genes to ovarian cancer diagnosed at age <30 years. Women with epithelial ovarian cancer were identified through cancer registries. DNA samples were analyzed for mutations in BRCA1, the "ovarian cancer-cluster region" (nucleotides 3139-7069) of BRCA2, and the mismatch-repair genes hMSH2 and hMLH1. Probable germline mutations in hMLH1 were identified in 2 (2%; 95% confidence interval 1%-8%) of 101 women with invasive ovarian cancer diagnosed at age <30 years. No germline mutations were identified in any of the other genes analyzed. There were no striking pedigrees suggestive of families with either breast/ovarian cancer or hereditary nonpolyposis colorectal cancer (HNPCC). There was a significantly increased incidence of all cancers in first-degree relatives of women with invasive disease (relative risk [RR] = 1.6, P=.01) but not in second-degree relatives or in relatives of women with borderline cases. First-degree relatives of women with invasive disease had increased risks of ovarian cancer (RR = 4.8, P=.03), myeloma (RR = 10, P=.01), and non-Hodgkin lymphoma (RR = 7, P=.004). Germline mutations in BRCA1, BRCA2, msh2, and mlh1 contribute to only a minority of cases of early-onset epithelial ovarian cancer. Our data suggest that early-onset ovarian cancer is not associated with a greatly increased risk of cancer in close relatives.