title: Reevaluation of the BRCA2 truncating allele c.9976A > T (p.Lys3326Ter) in a familial breast cancer context.
abstract: The breast cancer predisposition gene, BRCA2, has a large number of genetic variants of unknown effect. The variant rs11571833, an A > T transversion in the final exon of the gene that leads to the creation of a stop codon 93 amino acids early (K3326*), is reported as a neutral polymorphism but there is some evidence to suggest an association with an increased risk of breast cancer. We assessed whether this variant was enriched in a cohort of breast cancer cases ascertained through familial cancer clinics compared to population-based non-cancer controls using a targeted sequencing approach. We identified the variant in 66/2634 (2.5%) cases and 33/1996 (1.65%) controls, indicating an enrichment in the breast cancer cases (p = 0.047, OR 1.53, 95% CI 1.00-2.34). This data is consistent with recent iCOGs data suggesting that this variant is not neutral with respect to breast cancer risk. rs11571833 may need to be included in SNP panels for evaluating breast cancer risk.
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ella R
authors.initials: ER
authors.lastname: Thompson
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Department of Pathology University of Melbourne, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Gorringe
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Simone M
authors.initials: SM
authors.lastname: Rowley
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: McInerny
authors.affiliation: Discipline of Medical Genetics and Centre for Information-Based Medicine, The University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Wong-Brown
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Lifepool, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Devereux
authors.affiliation: Bioinformatics Core Facility, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Alison H
authors.initials: AH
authors.lastname: Trainer
authors.affiliation: Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.|Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.affiliation: Discipline of Medical Genetics and Centre for Information-Based Medicine, The University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.|Division of Genetics, Hunter Area Pathology Service, Newcastle, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Department of Pathology University of Melbourne, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.|Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: James
authors.affiliation: Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Department of Pathology University of Melbourne, Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Australia.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018389:Codon, Nonsense; D005091:Exons; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018389:Codon, Nonsense