Evaluation of breast cancer susceptibility loci in Chinese women.
Evaluation of breast cancer susceptibility loci in Chinese women.
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DOI：
10.1158/1055-9965.epi-10-0054
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发表时间：
2010-09
期刊：
影响因子：
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通讯作者：
Zheng W
中科院分区：
文献类型：
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作者：
Long J;Shu XO;Cai Q;Gao YT;Zheng Y;Li G;Li C;Gu K;Wen W;Xiang YB;Lu W;Zheng W
最近的全基因组关联研究（GWAS），主要是在欧洲血统的女性中进行的，已经确定了16个与乳腺癌相关的单核苷酸多态性（SNP）。我们评估了这些SNPs与乳腺癌的风险，并进一步通过雌激素受体（ER）状态在一项基于人群的研究中，6,498例病例和3,999例对照中国妇女。我们还在一项两阶段研究中，在2 q35、5 p12/MRPS 30、8q24.21和17q23.2/COX 11四个基因座中寻找新的遗传风险变异。在第一阶段，在2,073例病例和2,084例对照中分析了868个SNP。在第二阶段，从第一阶段中选择了58个SNPs进行评估，包括4，425例病例和1，915例对照。统计学显著相关性在GWAS鉴定的8个SNPs中，包括rs 4973768，（3p24/SLC4A7），rs889312（5q11.2MAP3K1），rs2046210（6q25.1）、rs 1219648（10q26.13FGFR2）、rs 2981582（10q26.13/FGFR 2）、rs3817198（11p15.5/LSP 1）、rs 8051542（16q12.1TOX3）和rs3803662（16q12.1/TOX 3）。另外两个SNP，rs 10941679（5 p12/MRPS 30）和rs 13281615（8q24.21）显示出轻微的显著关联。其中一些协会因ER状态而异。在精细作图分析中，5个SNP在两个阶段均与乳腺癌风险一致相关：rs 10169372（2 q35），rs 283720（8q24.21），rs 10515083（17q23.2/COX 11），rs 16955329（17q23.2/COX 11）和rs 2787487（17q23.2/COX 11）。这项研究表明，大约一半的SNPs最初报告的GWAS乳腺癌在欧洲后裔可以直接复制在中国。我们的精细映射分析揭示了几个候选的风险变异，可以在更大样本量的研究中进一步评估。这项研究的发现可能有助于指导未来的精细定位研究，以确定乳腺癌的因果变异。
Recent genome-wide association studies (GWAS), mostly conducted among women of European ancestry, have identified 16 single nucleotide polymorphisms (SNPs) associated with breast cancer. We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor (ER) status in a population-based study of 6,498 cases and 3,999 controls in Chinese women. We also searched for novel genetic risk variants in four loci, 2q35, 5p12/MRPS30, 8q24.21, and 17q23.2/COX11, in a two-stage study. In stage I, 868 SNPs were analyzed in 2,073 cases and 2,084 controls. In stage II, 58 SNPs selected from stage I were evaluated, including 4,425 cases and 1,915 controls. Statistically significant associations (P<0.05) were observed for 8 GWAS-identified SNPs, including rs4973768 (3p24/SLC4A7), rs889312 (5q11.2MAP3K1), rs2046210 (6q25.1), rs1219648 (10q26.13FGFR2), rs2981582 (10q26.13/FGFR2), rs3817198 (11p15.5/LSP1), rs8051542 (16q12.1TOX3), and rs3803662 (16q12.1/TOX3). Two additional SNPs, rs10941679 (5p12/MRPS30) and rs13281615 (8q24.21) showed a marginally significant association. Some of these associations varied by ER status. In the fine-mapping analysis, 5 SNPs showed a consistent association with breast cancer risk in both stages: rs10169372 (2q35), rs283720 (8q24.21), rs10515083 (17q23.2/COX11), rs16955329 (17q23.2/COX11), and rs2787487 (17q23.2/COX11). This study shows that approximately half of the SNPs initially reported from GWAS of breast cancer in European descendants can be directly replicated in Chinese. Our fine-mapping analyses revealed several candidates of risk variants that can be further evaluated in studies with a larger sample size. Findings from this study may help guide future fine-mapping studies to identify causal variants for breast cancer.