title: Breast cancer susceptibility variants alter risk in familial ovarian cancer.
abstract: Recent candidate gene and genome wide association studies have revealed novel loci associated with an increased risk of breast cancer. We evaluated the effect of these breast cancer associated variants on ovarian cancer risk in individuals with familial ovarian cancer both with and without BRCA1 or BRCA2 mutations. A total of 158 unrelated white British women (54 BRCA1/2 mutation positive and 104 BRCA1/2 mutation negative) with familial ovarian cancer were genotyped for FGFR2, TNRC9/TOX3 and CASP8 variants. The p.Asp302His CASP8 variant was associated with reduced ovarian cancer risk in the familial BRCA1/2 mutation negative ovarian cancer cases (P = 0.016). The synonymous TNRC9/TOX3 (Ser51) variant was present at a significantly lower frequency than in patients with familial BRCA1/2 positive breast cancer (P = 0.0002). Our results indicate that variants in CASP8 and TNRC9/TOX3 alter the risk of disease in individuals affected with familial ovarian cancer.
authors.affiliation: Genetic Medicine, Manchester Academic Heath Science Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, University of Manchester, Oxford Road, Manchester M13 9WL, UK.
authors.forename: A
authors.initials: A
authors.lastname: Latif
authors.forename: H J
authors.initials: HJ
authors.lastname: McBurney
authors.forename: S A
authors.initials: SA
authors.lastname: Roberts
authors.forename: F
authors.initials: F
authors.lastname: Lalloo
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: D G
authors.initials: DG
authors.lastname: Evans
authors.forename: W G
authors.initials: WG
authors.lastname: Newman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006609:High Mobility Group Proteins; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D015534:Trans-Activators; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D006609:High Mobility Group Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C505530:CASP8 protein, human; D053181:Caspase 8