Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
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 inclu...
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2012
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oai:doaj.org-article:f75dd7743701428380d28e90b51831792021-11-18T06:18:54ZGenome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.1553-73901553-740410.1371/journal.pgen.1002532https://doaj.org/article/f75dd7743701428380d28e90b51831792012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22383897/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Genetic 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.Jirong LongQiuyin CaiHyuna SungJiajun ShiBen ZhangJi-Yeob ChoiWanqing WenRyan J DelahantyWei LuYu-Tang GaoHongbing ShenSue K ParkKexin ChenChen-Yang ShenZefang RenChristopher A HaimanKeitaro MatsuoMi Kyung KimUi Soon KhooMotoki IwasakiYing ZhengYong-Bing XiangKai GuNathaniel RothmanWenjing WangZhibin HuYao LiuKeun-Young YooDong-Young NohBok-Ghee HanMin Hyuk LeeHong ZhengLina ZhangPei-Ei WuYa-Lan ShiehSum Yin ChanShenming WangXiaoming XieSung-Won KimBrian E HendersonLoic Le MarchandHidemi ItoYoshio KasugaSei-Hyun AhnHan Sung KangKelvin Y K ChanHiroji IwataShoichiro TsuganeChun LiXiao-Ou ShuDae-Hee KangWei ZhengPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 2, p e1002532 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Jirong Long Qiuyin Cai Hyuna Sung Jiajun Shi Ben Zhang Ji-Yeob Choi Wanqing Wen Ryan J Delahanty Wei Lu Yu-Tang Gao Hongbing Shen Sue K Park Kexin Chen Chen-Yang Shen Zefang Ren Christopher A Haiman Keitaro Matsuo Mi Kyung Kim Ui Soon Khoo Motoki Iwasaki Ying Zheng Yong-Bing Xiang Kai Gu Nathaniel Rothman Wenjing Wang Zhibin Hu Yao Liu Keun-Young Yoo Dong-Young Noh Bok-Ghee Han Min Hyuk Lee Hong Zheng Lina Zhang Pei-Ei Wu Ya-Lan Shieh Sum Yin Chan Shenming Wang Xiaoming Xie Sung-Won Kim Brian E Henderson Loic Le Marchand Hidemi Ito Yoshio Kasuga Sei-Hyun Ahn Han Sung Kang Kelvin Y K Chan Hiroji Iwata Shoichiro Tsugane Chun Li Xiao-Ou Shu Dae-Hee Kang Wei Zheng Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. |
| description |
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. |
| format |
article |
| author |
Jirong Long Qiuyin Cai Hyuna Sung Jiajun Shi Ben Zhang Ji-Yeob Choi Wanqing Wen Ryan J Delahanty Wei Lu Yu-Tang Gao Hongbing Shen Sue K Park Kexin Chen Chen-Yang Shen Zefang Ren Christopher A Haiman Keitaro Matsuo Mi Kyung Kim Ui Soon Khoo Motoki Iwasaki Ying Zheng Yong-Bing Xiang Kai Gu Nathaniel Rothman Wenjing Wang Zhibin Hu Yao Liu Keun-Young Yoo Dong-Young Noh Bok-Ghee Han Min Hyuk Lee Hong Zheng Lina Zhang Pei-Ei Wu Ya-Lan Shieh Sum Yin Chan Shenming Wang Xiaoming Xie Sung-Won Kim Brian E Henderson Loic Le Marchand Hidemi Ito Yoshio Kasuga Sei-Hyun Ahn Han Sung Kang Kelvin Y K Chan Hiroji Iwata Shoichiro Tsugane Chun Li Xiao-Ou Shu Dae-Hee Kang Wei Zheng |
| author_facet |
Jirong Long Qiuyin Cai Hyuna Sung Jiajun Shi Ben Zhang Ji-Yeob Choi Wanqing Wen Ryan J Delahanty Wei Lu Yu-Tang Gao Hongbing Shen Sue K Park Kexin Chen Chen-Yang Shen Zefang Ren Christopher A Haiman Keitaro Matsuo Mi Kyung Kim Ui Soon Khoo Motoki Iwasaki Ying Zheng Yong-Bing Xiang Kai Gu Nathaniel Rothman Wenjing Wang Zhibin Hu Yao Liu Keun-Young Yoo Dong-Young Noh Bok-Ghee Han Min Hyuk Lee Hong Zheng Lina Zhang Pei-Ei Wu Ya-Lan Shieh Sum Yin Chan Shenming Wang Xiaoming Xie Sung-Won Kim Brian E Henderson Loic Le Marchand Hidemi Ito Yoshio Kasuga Sei-Hyun Ahn Han Sung Kang Kelvin Y K Chan Hiroji Iwata Shoichiro Tsugane Chun Li Xiao-Ou Shu Dae-Hee Kang Wei Zheng |
| author_sort |
Jirong Long |
| title |
Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. |
| title_short |
Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. |
| title_full |
Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. |
| title_fullStr |
Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. |
| title_full_unstemmed |
Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. |
| title_sort |
genome-wide association study in east asians identifies novel susceptibility loci for breast cancer. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/f75dd7743701428380d28e90b5183179 |
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