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.

Occurrence of Two Rare Malignant Neoplasms (Breast and Ovarian) in an Adolescent Female

“…Just as 15% of women with breast adenocarcinoma under 30 years of age have an inherited BRCA mutation, it was thought that mutations in BRCA1/2 may be implicated in early onset epithelial ovarian cancer occurring in women # 30 years of age. 25 However, when tested for BRCA1/2, hMLH1, or hMSH2, only 2% of such women were found to have a germline mutation (hMLH1), suggesting that they may not be part of the familial breast/ovarian cancer syndrome. 25 Early-onset cancers have characteristics that are biologically distinct from ovarian cancer occurring in older women.…”

“…25 However, when tested for BRCA1/2, hMLH1, or hMSH2, only 2% of such women were found to have a germline mutation (hMLH1), suggesting that they may not be part of the familial breast/ovarian cancer syndrome. 25 Early-onset cancers have characteristics that are biologically distinct from ovarian cancer occurring in older women. They are more often borderline, multifocal, and less aggressive.…”

Genetic Testing by Cancer Site

“…6,8,35Y37 Unlike breast cancer, women with a diagnosis of very early-onset ovarian cancer (G40 years) are significantly less likely to harbor BRCA1/2 mutations. 8,26,35,38,39 This is in part due to the fact that early-onset ovarian cancers are more likely to be associated REVIEW ARTICLE 320 …”

A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

“…Nevertheless, about 15% of BRCA1-associated ovarian tumors are diagnosed in women over 70 [9,13,14].…”