Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.
Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast canc...
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2010-06-01
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doaj-88632a9f345d436daf4834b5f2ad43852020-11-25T00:07:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-06-0166e100100210.1371/journal.pgen.1001002Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.Jirong LongQiuyin CaiXiao-Ou ShuShimian QuChun LiYing ZhengKai GuWenjing WangYong-Bing XiangJiarong ChengKexin ChenLina ZhangHong ZhengChen-Yang ShenChiun-Sheng HuangMing-Feng HouHongbing ShenZhibin HuFuru WangSandra L DemingMark C KelleyMartha J ShrubsoleUi Soon KhooKelvin Y K ChanSum Yin ChanChristopher A HaimanBrian E HendersonLoic Le MarchandMotoki IwasakiYoshio KasugaShoichiro TsuganeKeitaro MatsuoKazuo TajimaHiroji IwataBo HuangJiajun ShiGuoliang LiWanqing WenYu-Tang GaoWei LuWei ZhengGenetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.http://europepmc.org/articles/PMC2891809?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jirong Long Qiuyin Cai Xiao-Ou Shu Shimian Qu Chun Li Ying Zheng Kai Gu Wenjing Wang Yong-Bing Xiang Jiarong Cheng Kexin Chen Lina Zhang Hong Zheng Chen-Yang Shen Chiun-Sheng Huang Ming-Feng Hou Hongbing Shen Zhibin Hu Furu Wang Sandra L Deming Mark C Kelley Martha J Shrubsole Ui Soon Khoo Kelvin Y K Chan Sum Yin Chan Christopher A Haiman Brian E Henderson Loic Le Marchand Motoki Iwasaki Yoshio Kasuga Shoichiro Tsugane Keitaro Matsuo Kazuo Tajima Hiroji Iwata Bo Huang Jiajun Shi Guoliang Li Wanqing Wen Yu-Tang Gao Wei Lu Wei Zheng |
spellingShingle |
Jirong Long Qiuyin Cai Xiao-Ou Shu Shimian Qu Chun Li Ying Zheng Kai Gu Wenjing Wang Yong-Bing Xiang Jiarong Cheng Kexin Chen Lina Zhang Hong Zheng Chen-Yang Shen Chiun-Sheng Huang Ming-Feng Hou Hongbing Shen Zhibin Hu Furu Wang Sandra L Deming Mark C Kelley Martha J Shrubsole Ui Soon Khoo Kelvin Y K Chan Sum Yin Chan Christopher A Haiman Brian E Henderson Loic Le Marchand Motoki Iwasaki Yoshio Kasuga Shoichiro Tsugane Keitaro Matsuo Kazuo Tajima Hiroji Iwata Bo Huang Jiajun Shi Guoliang Li Wanqing Wen Yu-Tang Gao Wei Lu Wei Zheng Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. PLoS Genetics |
author_facet |
Jirong Long Qiuyin Cai Xiao-Ou Shu Shimian Qu Chun Li Ying Zheng Kai Gu Wenjing Wang Yong-Bing Xiang Jiarong Cheng Kexin Chen Lina Zhang Hong Zheng Chen-Yang Shen Chiun-Sheng Huang Ming-Feng Hou Hongbing Shen Zhibin Hu Furu Wang Sandra L Deming Mark C Kelley Martha J Shrubsole Ui Soon Khoo Kelvin Y K Chan Sum Yin Chan Christopher A Haiman Brian E Henderson Loic Le Marchand Motoki Iwasaki Yoshio Kasuga Shoichiro Tsugane Keitaro Matsuo Kazuo Tajima Hiroji Iwata Bo Huang Jiajun Shi Guoliang Li Wanqing Wen Yu-Tang Gao Wei Lu Wei Zheng |
author_sort |
Jirong Long |
title |
Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. |
title_short |
Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. |
title_full |
Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. |
title_fullStr |
Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. |
title_full_unstemmed |
Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. |
title_sort |
identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the asia breast cancer consortium. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2010-06-01 |
description |
Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures. |
url |
http://europepmc.org/articles/PMC2891809?pdf=render |
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