Association of breast cancer with common variants in the BRCA2 gene an Afro-Barbadian population Free

B103

Significant evidence of inherited risk for breast cancer (bc) has been associated with deleterious mutations in BRCA1 and BRCA2 genes.
 Inherited mutations in BRCA1 and BRCA2 have been reported across multiple populations; however it is not known whether or not common variants in these genes influence breast cancer risk. We set out to determine if common variants in the BRCA2 gene were associated with breast cancer risk in the Afro-Caribbean population on the island of Barbados.
 We screened the coding region of BRCA2 for all variants in this gene in a sample of 95 female participants (43 cases and 52 female age-matched controls). A total of 27 variants were discovered in BRCA2. Approximately half (n=14) of the variants had minor allele frequencies (MAF) >5% and were also found in dbSNP. However, we discovered ten previously unreported variants, although representing relatively rare alleles (MAF<3%).
 To assess risk we genotyped 257 DNAs (89 BC cases and 168 female controls, all AB) with all discovered SNPs and 51 htSNPs selected from the HapMap encompassing the BRCA2 locus.
 The program Haploview was utilized to detect and quantify estimates of linkage disequilibrium (LD) between the marker loci, and to test for association between genotypes, haplotypes and disease status. Four of the 64 HapMap markers (6%) were uninformative in our population based upon our genotype data. We performed two analyses. Haplotypes were deduced for all markers (MAF>1%) or only for markers with a MAF>10%. One major haplotype block of 12 SNPs was identified. The average D' between the pairs of loci was 0.93, but the average R2 was only 0.22. When looking individually at all BRCA2 SNPs genotyped, there were six BRCA2 SNPs that showed nominally significant associations with BC risk, but these associations were not significant after permutation test (100 iterations). No haplotypes showed significant association with BC in these data.
 These data would suggest that common variation within the BRCA2 locus does not confer increased risk of breast cancer in the Afro-Barbadian population. However, a larger cohort may be needed to completely rule this locus out as being a contributor to breast cancer in Barbados.