- Antoniou, Antonis C., et al.
Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for <em>BRCA1</em> and <em>BRCA2</em> Mutation Carriers : Implications for Risk Prediction
Ingår i: Cancer Research. - American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
- <p>The known breast cancer susceptibility polymorphisms in <em>FGFR2</em>, <em>TNRC9/TOX3</em>, <em>MAP3K1</em>, <em>LSP1</em>, and 2q35 confer increased risks of breast cancer for <em>BRCA1</em> or <em>BRCA2</em> mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in <em>SLC4A7/NEK10</em>, rs6504950 in <em>STXBP4/COX11</em>, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 <em>BRCA1</em> and 7,409 <em>BRCA2</em> carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for <em>BRCA2</em> carriers (per-allele HR = 1.10, 95% CI: 1.03–1.18, <em>P</em> = 0.006 and HR = 1.09, 95% CI: 1.01–1.19, <em>P</em> = 0.03, respectively). Neither SNP was associated with breast cancer risk for <em>BRCA1</em> carriers, and rs6504950 was not associated with breast cancer for either <em>BRCA1</em> or <em>BRCA2</em> carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for <em>BRCA2</em> carriers (<em>FGFR2, TOX3, MAP3K1, LSP1</em>, 2q35<em>, SLC4A7</em>, 5p12, <em>P</em> = 7 × 10<sup>−11</sup> − 0.03), but only <em>TOX3</em> and 2q35 were associated with the risk for <em>BRCA1</em> carriers (<em>P</em> = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in <em>BRCA2</em> mutation carriers, the 5% of <em>BRCA2</em> carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers. <em>Cancer Res; 70(23); 9742–54. ©2010 AACR</em>.</p>