title: Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer.
abstract: BACKGROUND
  BRIP1 interacts with BRCA1 and functions in regulating DNA double strand break repair pathways. Germline BRIP1 mutations are associated with breast cancer and Fanconi anemia. Thus, common variants in the BRIP1 are candidates for breast and ovarian cancer susceptibility.
  
  
  METHODS
  We used a SNP tagging approach to evaluate the association between common variants (minor allele frequency>or=0.05) in BRIP1 and the risks of breast cancer and invasive ovarian cancer. 12 tagging SNPs (tSNPs) in the gene were identified and genotyped in up to 2,270 breast cancer cases and 2,280 controls from the UK and up to 1,513 invasive ovarian cancer cases and 2,515 controls from the UK, Denmark and USA. Genotype frequencies in cases and controls were compared using logistic regression.
  
  
  RESULTS
  Two tSNPs showed a marginal significant association with ovarian cancer: Carriers of the minor allele of rs2191249 were at reduced risk compared with the common homozygotes (Odds Ratio (OR) = 0.90 (95% CI, 0.82-1.0), P-trend = 0.045) and the minor allele of rs4988344 was associated with increased risk (OR = 1.15 (95%CI, 1.02-1.30), P-trend = 0.02). When the analyses were restricted to serous ovarian cancers, these effects became slightly stronger. These results were not significant at the 5% level after adjusting for multiple testing. None of the tSNPs was associated with breast cancer.
  
  
  CONCLUSIONS
  It is unlikely that common variants in BRIP1 contribute significantly to breast cancer susceptibility. The possible association of rs2191249 and rs4988344 with ovarian cancer risks warrant confirmation in independent case-control studies.
authors.affiliation: Cancer Research UK (CRUK) Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. honglin@srl.cam.ac.uk
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Susanne Krüger
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Estrid
authors.initials: E
authors.lastname: Hogdall
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dicioccio
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.forename: Claus
authors.initials: C
authors.lastname: Hogdall
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jacobs
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020365:RNA Helicases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C000618935:BRIP1 protein, human; D020365:RNA Helicases