Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer.
BACKGROUND
Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer.


METHODS
We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls).


RESULTS
One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02-1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women.


CONCLUSIONS
We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear.
Cox
David G
DG
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. dcox@hsph.harvard.edu
Kraft
Peter
P
Hankinson
Susan E
SE
Hunter
David J
DJ
D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
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