Song, HL;
Ramus, SJ;
Kjaer, SK;
Hogdall, E;
DiCioccio, RA;
Whittemore, AS;
McGuire, V;
... Pharoah, PDP; + view all
(2007)
Tagging Single Nucleotide Polymorphisms in the BRIP1 Gene and Susceptibility to Breast and Ovarian Cancer.
PLOS ONE
, 2
(3)
, Article e268. 10.1371/journal.pone.0000268.
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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 >= 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.
| Type: | Article |
|---|---|
| Title: | Tagging Single Nucleotide Polymorphisms in the BRIP1 Gene and Susceptibility to Breast and Ovarian Cancer |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0000268 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0000268 |
| Language: | English |
| Additional information: | © 2007 Song et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was funded by grants from Cancer Research UK, the Roswell Park Alliance, the Danish Cancer Society and the National Cancer Institute (CA71766 and Core Grant CA16056 and RO1 CA61107). HS was funded by a grant from WellBeing; BAJP is a Gibb Fellow, DFE is a Principal Research Fellow and PDPP is a Senior Clinical Research Fellow of Cancer Research UK; SAG is a HEFCE Funded Senior lecturer; SJR is funded by the Mermaid component of the Eve Appeal. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/176700 |
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