Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer.
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.
Song
Honglin
H
Cancer Research UK (CRUK) Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. honglin@srl.cam.ac.uk
Ramus
Susan J
SJ
Kjaer
Susanne Krüger
SK
Hogdall
Estrid
E
Dicioccio
Richard A
RA
Whittemore
Alice S
AS
McGuire
Valerie
V
Hogdall
Claus
C
Jacobs
Ian J
IJ
Easton
Douglas F
DF
Ponder
Bruce A J
BA
Dunning
Alison M
AM
Gayther
Simon A
SA
Pharoah
Paul D P
PD
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
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C000618935:BRIP1 protein, human; D020365:RNA Helicases