Genetic polymorphisms inAURKAandBRCA1are associated with breast cancer susceptibility in a Chinese Han population

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Abstract

Centrosome defects can result in aneuploidy and genomic instability, and have important implications for breast cancer development. The Aurora-A and BRCA1 proteins interact and both are strongly involved in centrosome regulation. Genetic variants in these two genes may have an effect on breast cancer development. Here, we report a comprehensive single nucleotide polymorphism (SNP) and haplotype-tagging association study on these two genes in 1334 breast cancer cases and 1568 unaffected controls among the Chinese Han population. Apart from a missense SNP, rs2273535 (Phe31Ile), and a probable risk SNP, rs2064863, six htSNPs were analysed in three high-LD blocks ofAURKAspanning from 10 kb upstream to 2 kb downstream ofAURKA. ForBRCA1,six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end ofBRCA1). The results showed that four SNPs inAURKA(data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03–4.66,p= 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18–0.82,p= 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18–2.00,p= 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47–0.98,p= 0.0380) and one SNP inBRCA1(rs3737559, dominant model OR = 1.35, 95% CI = 1.11–1.64,p= 0.0030) were associated with breast cancer susceptibility. After correction for multiple comparisons (FDR = 0.05), only rs6024836 and rs3737559 remained significant. Two haplotypes (CC of block 2, OR = 20.74, 95% CI = 4.35–98.88,p= 0.0001; GG of block 3, OR = 1.32, 95% CI = 1.12–1.56,p= 0.0010) and one diplotype (AG-GG of block 3, OR = 1.63, 95% CI = 1.18–2.26,p= 0.0031) withinAURKAshowed strong associations with breast cancer risk. One haplotype ofBRCA1(CTGTTG, OR = 1.30, 95% CI = 1.06–1.59,p= 0.0118) was also associated with breast cancer risk. However, women harbouring both at-risk genotypes ofAurora-AandBRCA1were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in theAURKAandBRCA1genes may contribute to breast cancer development. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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