Identification of a Functional Genetic Variant at 16q12.1 for Breast Cancer Risk: Results from the Asia Breast Cancer Consortium

被引：95

作者：

Long, Jirong ^{[1
]}

Cai, Qiuyin ^{[1
]}

Shu, Xiao-Ou ^{[1
]}

Qu, Shimian ^{[1
]}

Li, Chun ^{[2
]}

Zheng, Ying ^{[3
]}

Gu, Kai ^{[3
]}

Wang, Wenjing ^{[3
]}

Xiang, Yong-Bing ^{[4
]}

Cheng, Jiarong ^{[4
]}

Chen, Kexin ^{[5
]}

Zhang, Lina ^{[5
]}

Zheng, Hong ^{[5
]}

Shen, Chen-Yang ^{[6
]}

Huang, Chiun-Sheng ^{[6
]}

Hou, Ming-Feng ^{[6
]}

Shen, Hongbing ^{[7
]}

Hu, Zhibin ^{[7
]}

Wang, Furu ^{[7
]}

Deming, Sandra L. ^{[1
]}

Kelley, Mark C. ^{[8
]}

Shrubsole, Martha J. ^{[1
]}

Khoo, Ui Soon ^{[9
]}

Chan, Kelvin Y. K. ^{[8
]}

Chan, Sum Yin ^{[9
]}

Haiman, Christopher A. ^{[10
]}

Henderson, Brian E. ^{[10
]}

Le Marchand, Loic ^{[11
]}

Iwasaki, Motoki ^{[12
]}

Kasuga, Yoshio ^{[13
]}

Tsugane, Shoichiro ^{[12
]}

Matsuo, Keitaro ^{[14
]}

Tajima, Kazuo ^{[14
]}

Iwata, Hiroji ^{[15
]}

Huang, Bo ^{[1
]}

Shi, Jiajun ^{[1
]}

Li, Guoliang ^{[1
]}

Wen, Wanqing ^{[1
]}

Gao, Yu-Tang ^{[4
]}

Lu, Wei ^{[3
]}

Zheng, Wei ^{[1
]}

机构：

[1] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA

[2] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA

[3] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China

[4] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China

[5] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin, Peoples R China

[6] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[7] Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Peoples R China

[8] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Surg Oncol, Nashville, TN 37212 USA

[9] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China

[10] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA

[11] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA

[12] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan

[13] Nagano Matsushiro Gen Hosp, Dept Surg, Nagano, Japan

[14] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan

[15] Cent Hosp, Aichi Canc Ctr, Dept Breast Oncol, Nagoya, Aichi, Japan

来源：

PLOS GENETICS | 2010年 / 6卷 / 06期

关键词：

GENOME-WIDE ASSOCIATION; CHINESE WOMEN; CONFER SUSCEPTIBILITY; COMMON VARIANTS; POLYMORPHISMS; ALLELES; LOCUS;

D O I：

10.1371/journal.pgen.1001002

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 = 3.2x10(-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 = 1.3x10(-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.

引用

页码：1 / 9

页数：9

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