Human Molecular Genetics Advance Access published online on August 18, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh270
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 MIT/Broad Institute, Cambridge, Massachusetts, USA; Departments of Medicine and Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
* To whom correspondence should be addressed. E-mail: Haiman{at}usc.edu.
It is well established that rare mutations in BRCA2 predispose to familial breast cancer, but whether common variants at this locus contribute more modest risk to sporadic breast cancer has not been thoroughly investigated. We performed a haplotype-based study of BRCA2 among women in the Multiethnic Cohort Study (MEC), genotyping 50 SNPs spanning 109.4 kb of the BRCA2 gene. Twenty-one haplotype-tagging SNPs (htSNPs), (including 7 missense SNPs), were selected to predict the common BRCA2 haplotypes and genotyped in a breast cancer case-control study nested in the MEC (cases, n=1,715; controls, n=2,502). Compared to non-carriers, we observed nominally significant positive associations for homozygous carriers of specific haplotypes in blocks 2 (haplotype 2c: OR=1.50; 95% CI, 1.08-2.09) and 3 (haplotype 3d: OR=1.50; 95% CI, 1.01-2.24). These results could be explained based on a single marker in intron 24 (SNP 42: rs206340) that was correlated with these haplotypes and the homozygous state was associated with a significantly increased risk of breast cancer (AA vs GG genotypes: OR=1.59, 95% CI, 1.18-2.16; nominal P=0.005). This association was modestly stronger among women with advanced disease (OR=2.00, 95% CI, 1.30-3.08; P=0.002). In this exploratory analysis, we found little indication that common variation in BRCA2 dramatically impacts sporadic breast cancer risk. However, a significant elevation in risk was observed among
Article
Common variation in BRCA2 and breast cancer risk: A haplotype-based analysis in the multiethnic cohort
2 MIT/Broad Institute, Cambridge, Massachusetts, USA
3 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
4 Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, USA
5 MIT/Broad Institute, Cambridge, Massachusetts, USA; Divisions of Genetics and Endocrinology, Children's Hospital, Boston, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
6 MIT/Broad Institute, Cambridge, Massachusetts, USA; Departments of Medicine and Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Molecular Biology and Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts USA
7 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Ave., Rm. 4441, Los Angeles, California, 90089-9175, USA
Abstract 
6% of women who carried a specific haplotype pattern and may harbor a susceptibility allele at the BRCA2 locus.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. A. Haiman, C. Hsu, P. I.W. de Bakker, M. Frasco, X. Sheng, D. Van Den Berg, J. T. Casagrande, L. N. Kolonel, L. Le Marchand, S. E. Hankinson, et al. Comprehensive association testing of common genetic variation in DNA repair pathway genes in relationship with breast cancer risk in multiple populations Hum. Mol. Genet., March 15, 2008; 17(6): 825 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. W. Setiawan, I. Cheng, D. O. Stram, E. Giorgi, M. C. Pike, D. Van Den Berg, L. Pooler, N. P. Burtt, L. Le Marchand, D. Altshuler, et al. A Systematic Assessment of Common Genetic Variation in CYP11A and Risk of Breast Cancer Cancer Res., December 15, 2006; 66(24): 12019 - 12025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 The Breast Cancer Association Consortium Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst, October 4, 2006; 98(19): 1382 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Haiman, D. O. Stram, I. Cheng, E. E. Giorgi, L. Pooler, K. Penney, L. Le Marchand, B. E. Henderson, and M. L. Freedman Common Genetic Variation at PTEN and Risk of Sporadic Breast and Prostate Cancer. Cancer Epidemiol. Biomarkers Prev., May 1, 2006; 15(5): 1021 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Millikan, J. S. Player, A. R. deCotret, C.-K. Tse, and T. Keku Polymorphisms in DNA Repair Genes, Medical Exposure to Ionizing Radiation, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2005; 14(10): 2326 - 2334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Freedman, K. L. Penney, D. O. Stram, S. Riley, R. McKean-Cowdin, L. Le Marchand, D. Altshuler, and C. A. Haiman A Haplotype-Based Case-Control Study of BRCA1 and Sporadic Breast Cancer Risk Cancer Res., August 15, 2005; 65(16): 7516 - 7522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Cox, S. E. Hankinson, and D. J. Hunter No Association between BRCA2 N372H and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1353 - 1354. [Full Text] [PDF]
|
|