OBJECTIVE: Our purpose was to determine the prevalence of BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in a large, unselected population of ovarian cancer patients and to evaluate the relationship between mutation status and a routinely obtained family history of cancer. STUDY DESIGN: One hundred sixteen consecutive ovarian cancer patients seen for routine clinical care were examined for BRCA1, BRCA2, hMSH2, and hMLH1 gene mutations with use of the polymerase chain reaction, single-strand conformation polymorphism analysis, and direct gene sequencing. Fisher's exact test was used to evaluate possible associations between BRCA1 and BRCA2 mutation status and specific familial characteristics. RESULTS: Among 116 unselected ovarian cancer patients we identified a total of 13 germline mutations in 12 patients: 10 in BRCA1, one each in hMSH2 and hMLH1, and a single BRCA2 mutation, which occurred in a patient also carrying a BRCA1 mutation. More than half the patients with BRCA1 mutations had family histories that would generally be considered unremarkable. Of 22 family history variables analyzed, only two (maternal family history of breast or ovarian cancer, p=0.037, and maternal family history of any cancer, p=0.020) conferred a significantly increased risk of carrying a BRCA1 mutation compared with ovarian cancer patients without such a history. However, the majority of ovarian cancer patients with these family histories and other suggestive histories tested negative for mutations. CONCLUSIONS: Approximately 10% of ovarian cancers occur in association with genetic mutations known to predispose to the disease. A routinely obtained family history is an unreliable way to identify patients who might harbor mutations. The majority of ovarian cancer patients with suggestive family histories test negative for known gene mutations, perhaps suggesting the existence of additional undiscovered genes predisposing to ovarian cancer.
OBJECTIVE: Our purpose was to determine the prevalence of BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in a large, unselected population of ovarian cancerpatients and to evaluate the relationship between mutation status and a routinely obtained family history of cancer. STUDY DESIGN: One hundred sixteen consecutive ovarian cancerpatients seen for routine clinical care were examined for BRCA1, BRCA2, hMSH2, and hMLH1 gene mutations with use of the polymerase chain reaction, single-strand conformation polymorphism analysis, and direct gene sequencing. Fisher's exact test was used to evaluate possible associations between BRCA1 and BRCA2 mutation status and specific familial characteristics. RESULTS: Among 116 unselected ovarian cancerpatients we identified a total of 13 germline mutations in 12 patients: 10 in BRCA1, one each in hMSH2 and hMLH1, and a single BRCA2 mutation, which occurred in a patient also carrying a BRCA1 mutation. More than half the patients with BRCA1 mutations had family histories that would generally be considered unremarkable. Of 22 family history variables analyzed, only two (maternal family history of breast or ovarian cancer, p=0.037, and maternal family history of any cancer, p=0.020) conferred a significantly increased risk of carrying a BRCA1 mutation compared with ovarian cancerpatients without such a history. However, the majority of ovarian cancerpatients with these family histories and other suggestive histories tested negative for mutations. CONCLUSIONS: Approximately 10% of ovarian cancers occur in association with genetic mutations known to predispose to the disease. A routinely obtained family history is an unreliable way to identify patients who might harbor mutations. The majority of ovarian cancerpatients with suggestive family histories test negative for known gene mutations, perhaps suggesting the existence of additional undiscovered genes predisposing to ovarian cancer.
Authors: Michael S Goldberg; Deyin Xing; Yin Ren; Sandra Orsulic; Sangeeta N Bhatia; Phillip A Sharp Journal: Proc Natl Acad Sci U S A Date: 2010-12-27 Impact factor: 11.205
Authors: Monica R McClain; Glenn E Palomaki; Heather Hampel; Judith A Westman; James E Haddow Journal: Fam Cancer Date: 2008-02-23 Impact factor: 2.375
Authors: David J Gallagher; Angel M Cronin; Matthew I Milowsky; Michael J Morris; Jasmine Bhatia; Peter T Scardino; James A Eastham; Kenneth Offit; Mark E Robson Journal: BJU Int Date: 2011-07-14 Impact factor: 5.588
Authors: Tadeusz Majewski; Sangkyou Lee; Joon Jeong; Dong-Sup Yoon; Andrzej Kram; Mi-Sook Kim; Tomasz Tuziak; Jolanta Bondaruk; Sooyong Lee; Weon-Seo Park; Kuang S Tang; Woonbok Chung; Lanlan Shen; Saira S Ahmed; Dennis A Johnston; H Barton Grossman; Colin P Dinney; Jain-Hua Zhou; R Alan Harris; Carrie Snyder; Slawomir Filipek; Steven A Narod; Patrice Watson; Henry T Lynch; Adi Gazdar; Menashe Bar-Eli; Xifeng F Wu; David J McConkey; Keith Baggerly; Jean-Pierre Issa; William F Benedict; Steven E Scherer; Bogdan Czerniak Journal: Lab Invest Date: 2008-05-05 Impact factor: 5.662
Authors: Henry T Lynch; Murray Joseph Casey; Carrie L Snyder; Chhanda Bewtra; Jane F Lynch; Matthew Butts; Andrew K Godwin Journal: Mol Oncol Date: 2009-02-21 Impact factor: 6.603