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. 2007 Mar 7;2(3):e268.
doi: 10.1371/journal.pone.0000268.

Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer

Honglin Song  1 , Susan J Ramus, Susanne Krüger Kjaer, Estrid Hogdall, Richard A Dicioccio, Alice S Whittemore, Valerie McGuire, Claus Hogdall, Ian J Jacobs, Douglas F Easton, Bruce A J Ponder, Alison M Dunning, Simon A Gayther, Paul D P Pharoah
Affiliations

Tagging single nucleotide polymorphisms in the BRIP1 gene and susceptibility to breast and ovarian cancer

Honglin Song et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Linkage disequilibrium between the 92 common variants (MAF>0.05) in HapMap CEPH trios.
Each square represents the correlation (r2) between each pair of SNPs with darker shades representing stronger LD. Tag SNPs are indicated with those SNPs that failed assay design being shown in grey font.
See this image and copyright information in PMC

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References

    1. Lynch HT, Casey MJ, Lynch J, White TE, Godwin AK. Genetics and ovarian carcinoma. Semin.Oncol, 1998;25:265–280. - PubMed
    1. Rahman N, Stratton MR. The genetics of breast cancer susceptibility. Annu Rev Genet, 1998;32:95–121. - PubMed
    1. Easton DF. How many more breast cancer predisposition genes are there? Breast Cancer Res, 1999;1:14–17. - PMC - PubMed
    1. Pharoah PD, Ponder BA. The genetics of ovarian cancer. Best Pract.Res Clin Obstet Gynaecol., 2002;16:449–468. - PubMed
    1. Smith P, McGuffog L, Easton DF, Mann GJ, Pupo GM, et al. A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer. 2006;45:646–55. - PMC - PubMed

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