Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population
Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population
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DOI：
10.1002/path.2902
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发表时间：
2011-12-01
影响因子：
7.3
通讯作者：
Fang, Wei-Gang
中科院分区：
文献类型：
--
作者：
Ruan, Yuan;Song, Ai-Ping;Fang, Wei-Gang
中心体缺陷可导致非整倍体和基因组不稳定，并对乳腺癌的发展具有重要意义。Aurora-A和BRCA1蛋白相互作用，两者都强烈参与中心体调节。这两个基因的基因变异可能对乳腺癌的发展有影响。在这里，我们报道了在中国汉族人群中1334例乳腺癌病例和1568例未受影响的对照中，这两个基因的单核苷酸多态性（SNP）和单倍型标记关联研究。除了错义SNP rs2273535 （Phe31Ile）和可能的风险SNP rs2064863外，在AURKA的三个高ld块中分析了6个htsnp，范围从AURKA上游10 kb到下游2 kb。对于BRCA1，在覆盖98 kb的大高ld区域分析了6个htsnp （BRCA1每端延伸10 kb）。结果表明,四个SNP AURKA(数据在隐性的模型中,rs2273535: = 2.19, 95% CI -4.66 = 1.03, p = 0.0422; rs2298016: = 0.38, 95% CI -0.82 = 0.18, p = 0.0141; rs6024836: = 1.54, 95% CI -2.00 = 1.18, p = 0.0014; rs10485805: = 0.68, 95% CI -0.98 = 0.47, p = 0.0380)和一个SNP在BRCA1 (rs3737559,占主导地位的模型或= 1.35,95% CI -1.64 = 1.11, p = 0.0030)与乳腺癌易感性有关。经多次比较校正（FDR = 0.05），只有rs6024836和rs3737559仍然具有显著性。AURKA内的两个单倍型（block 2的CC， OR = 20.74, 95% CI = 4.35-98.88, p = 0.0001； block 3的GG， OR = 1.32, 95% CI = 1.12-1.56, p = 0.0010）和一个双倍型（block 3的AG-GG， OR = 1.63, 95% CI = 1.18-2.26, p = 0.0031）与乳腺癌风险有很强的相关性。BRCA1的一种单倍型（CTGTTG, OR = 1.30, 95% CI = 1.06-1.59, p = 0.0118）也与乳腺癌风险相关。然而，同时携带Aurora-A和BRCA1高危基因型的女性患乳腺癌的风险比仅携带其中一种高危基因型的女性略高。AURKA和BRCA1基因的常见遗传变异可能与乳腺癌的发展有关。版权所有(C) 2011英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
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 of AURKA spanning from 10 kb upstream to 2 kb downstream of AURKA. For BRCA1, six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end of BRCA1). The results showed that four SNPs in AURKA (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 in BRCA1 (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) within AURKA showed strong associations with breast cancer risk. One haplotype of BRCA1 (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 of Aurora-A and BRCA1 were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in the AURKA and BRCA1 genes may contribute to breast cancer development. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.