title: Frequency of germline PALB2 mutations among women with epithelial ovarian cancer.
abstract: Recent studies suggest that mutations in the partner and localizer of BRCA2 (PALB2) gene may predispose to ovarian cancer. It is of importance to clarify the prevalence and penetrance of PALB2 mutations in an unselected population so that clinical recommendations for prevention can be implemented. We evaluated the prevalence of germline mutations in PALB2 among 1421 epithelial ovarian cancer patients and 4300 European controls from the National Heart, Lung, and Blood Institute's Exome Sequencing Project dataset. Clinical information was obtained from medical records and survival status was determined by linkage. PALB2 coding exons were sequenced using next generation sequencing technology. Of the 1421 patients, three (0.21 %) had a germline PALB2 mutation compared to two of the 4300 control subjects (0.05 %). The mean age at diagnosis was 59 years (range 55-62) and all three women died within 2 years of diagnosis. A PALB2 mutation was associated with a four-fold, albeit not significant, increased risk of ovarian cancer (OR = 4.55; 95 % CI 0.76-27.24; P = 0.10). These results suggest that germline PALB2 mutations are rare. The true effect of such mutations on ovarian cancer risk require further study before the clinical relevance of inherited PALB2 mutations is established.
authors.affiliation: Women's College Research Institute, Women's College Hospital, 76 Grenville St, 6th Floor, Room# 6421, Toronto, ON, M5S 1B2, Canada.|Dalla Lana School of Public Health, University of Toronto, 155 College Street Health Science Building, 6th Floor, Toronto, ON, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.affiliation: Women's College Research Institute, Women's College Hospital, 76 Grenville St, 6th Floor, Room# 6421, Toronto, ON, M5S 1B2, Canada.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sopik
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, Canada.|Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Main Floor Room 719, 610 University Ave, Toronto, ON, Canada.
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, Canada.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fan
authors.affiliation: Public Health Ontario, Toronto, ON, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: McLaughlin
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, 60 College St., New Haven, CT, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.affiliation: Women's College Research Institute, Women's College Hospital, 76 Grenville St, 6th Floor, Room# 6421, Toronto, ON, M5S 1B2, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Women's College Research Institute, Women's College Hospital, 76 Grenville St, 6th Floor, Room# 6421, Toronto, ON, M5S 1B2, Canada.|Dalla Lana School of Public Health, University of Toronto, 155 College Street Health Science Building, 6th Floor, Toronto, ON, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: Women's College Research Institute, Women's College Hospital, 76 Grenville St, 6th Floor, Room# 6421, Toronto, ON, M5S 1B2, Canada. mohammad.akbari@utoronto.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street Health Science Building, 6th Floor, Toronto, ON, Canada. mohammad.akbari@utoronto.ca.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D059645:Mutation Rate; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D009864:Ontario; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
keywords: Hereditary; Ovarian cancer; PALB2