Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
复制标题
东亚人的全基因组关联研究确定了乳腺癌的新易感位点
DOI：
10.1371/journal.pgen.1002532
复制
发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Zheng W
中科院分区：
文献类型：
--
作者：
Long J;Cai Q;Sung H;Shi J;Zhang B;Choi JY;Wen W;Delahanty RJ;Lu W;Gao YT;Shen H;Park SK;Chen K;Shen CY;Ren Z;Haiman CA;Matsuo K;Kim MK;Khoo US;Iwasaki M;Zheng Y;Xiang YB;Gu K;Rothman N;Wang W;Hu Z;Liu Y;Yoo KY;Noh DY;Han BG;Lee MH;Zheng H;Zhang L;Wu PE;Shieh YL;Chan SY;Wang S;Xie X;Kim SW;Henderson BE;Le Marchand L;Ito H;Kasuga Y;Ahn SH;Kang HS;Chan KY;Iwata H;Tsugane S;Li C;Shu XO;Kang DH;Zheng W
遗传因素在散发性和家族性乳腺癌的病因中起着重要作用。我们的目标是发现乳腺癌的新的遗传易感基因。我们对包括中国、韩国和日本女性在内的20,606名东亚血统患者和20,606名对照进行了一项分四个阶段的全基因组关联研究。在分析了2,918例患者和2,324名对照中的690,947个SNPs后，我们评估了3,972名患者和3,852名对照中5,365个SNP的复制情况。在5,203名患者和5,138名对照中对94个SNPs进行了进一步评估，最后在多达17,423名受试者(7,489名患者和9,934名对照)中调查了前22个SNPs。SNP rs9485372位于染色体6q25.1上转化生长因子-β激活激酶(TAB2)基因附近，在所有样本的联合分析中，与乳腺癌风险的相关性一致，P值为3.8x10−12。与G/G基因型相比，A/G和A/A基因型的校正优势比(95%可信区间)分别为0.89(0.85~0.94)和0.80(0.75~0.86)。位于ESR1基因第5内含子的SNP rs9383951(P = 1.9×10−6)和位于11q24.3的SNP rs7107217(P = 4.6×10−7)也显示出一致的关联。本研究为乳腺癌易感基因rs9485372在TAB2基因(6q25.1)附近提供了强有力的证据，并发现了两个可能的易感基因，分别位于ESR1基因和11q24.3。
Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10−12 in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10−6 from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10−7), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.
登录
查看更多内容
DOI：
10.1158/1055-9965.epi-10-0054
发表时间：
2010-09
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
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
通讯作者：
Zheng W
影响因子：
4.5
作者：
Long J;Cai Q;Shu XO;Qu S;Li C;Zheng Y;Gu K;Wang W;Xiang YB;Cheng J;Chen K;Zhang L;Zheng H;Shen CY;Huang CS;Hou MF;Shen H;Hu Z;Wang F;Deming SL;Kelley MC;Shrubsole MJ;Khoo US;Chan KY;Chan SY;Haiman CA;Henderson BE;Le Marchand L;Iwasaki M;Kasuga Y;Tsugane S;Matsuo K;Tajima K;Iwata H;Huang B;Shi J;Li G;Wen W;Gao YT;Lu W;Zheng W
通讯作者：
Zheng W
影响因子：
30.8
作者：
Stacey, Simon N.;Manolescu, Andrei;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
4.5
作者：
Stacey SN;Sulem P;Zanon C;Gudjonsson SA;Thorleifsson G;Helgason A;Jonasdottir A;Besenbacher S;Kostic JP;Fackenthal JD;Huo D;Adebamowo C;Ogundiran T;Olson JE;Fredericksen ZS;Wang X;Look MP;Sieuwerts AM;Martens JW;Pajares I;Garcia-Prats MD;Ramon-Cajal JM;de Juan A;Panadero A;Ortega E;Aben KK;Vermeulen SH;Asadzadeh F;van Engelenburg KC;Margolin S;Shen CY;Wu PE;Försti A;Lenner P;Henriksson R;Johansson R;Enquist K;Hallmans G;Jonsson T;Sigurdsson H;Alexiusdottir K;Gudmundsson J;Sigurdsson A;Frigge ML;Gudmundsson L;Kristjansson K;Halldorsson BV;Styrkarsdottir U;Gulcher JR;Hemminki K;Lindblom A;Kiemeney LA;Mayordomo JI;Foekens JA;Couch FJ;Olopade OI;Gudbjartsson DF;Thorsteinsdottir U;Rafnar T;Johannsson OT;Stefansson K
通讯作者：
Stefansson K
影响因子：
8
作者：
Stevens, T. A.;Meech, R.
通讯作者：
Meech, R.