title: The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study.
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.
authors.affiliation: WellBeing Ovarian Cancer Research Centre, University of Cambridge, Cambridge CB2 2XY, United Kingdom.
authors.forename: J F
authors.initials: JF
authors.lastname: Stratton
authors.forename: D
authors.initials: D
authors.lastname: Thompson
authors.forename: L
authors.initials: L
authors.lastname: Bobrow
authors.forename: N
authors.initials: N
authors.lastname: Dalal
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.forename: D T
authors.initials: DT
authors.lastname: Bishop
authors.forename: I
authors.initials: I
authors.lastname: Scott
authors.forename: G
authors.initials: G
authors.lastname: Evans
authors.forename: P
authors.initials: P
authors.lastname: Daly
authors.forename: D F
authors.initials: DF
authors.lastname: Easton
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D024682:BRCA2 Protein; D002352:Carrier Proteins; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D009687:Nuclear Proteins; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D024682:BRCA2 Protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein