Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

被引：64

作者：

Conti, David V. ^{[1
]}

Wang, Kan ^{[1
]}

Sheng, Xin ^{[1
]}

Bensen, Jeannette T. ^{[3
,4
]}

Hazelett, Dennis J. ^{[5
]}

Cook, Michael B. ^{[6
]}

Ingles, Sue A. ^{[1
,2
]}

Kittles, Rick A. ^{[7
,8
]}

Strom, Sara S. ^{[9
]}

Rybicki, Benjamin A. ^{[10
]}

Nemesure, Barbara ^{[11
]}

Isaacs, William B. ^{[12
]}

Stanford, Janet L. ^{[13
,14
]}

Zheng, Wei ^{[15
]}

Sanderson, Maureen ^{[16
]}

John, Esther M. ^{[17
,18
]}

Park, Jong Y. ^{[19
]}

Xu, Jianfeng ^{[20
,21
]}

Stevens, Victoria L. ^{[22
]}

Berndt, Sonja I. ^{[6
]}

Haiman, Christopher A. ^{[1
,2
]}

机构：

[1] Univ Southern Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA USA

[2] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[3] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA

[4] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[5] Cedars Sinai Med Ctr, Bioinformat & Computat Biol Res Ctr, Biomed Sci, Los Angeles, CA 90048 USA

[6] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[7] Univ Arizona, Coll Med, Tucson, AZ USA

[8] Univ Arizona, Ctr Canc, Tucson, AZ USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[10] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA

[11] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA

[12] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA

[13] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[14] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA

[15] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA

[16] Meharry Med Coll, Dept Family & Community Med, Nashville, TN 37208 USA

[17] Calif Prevent Inst Calif, Fremont, CA USA

[18] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford Canc Inst, Stanford, CA 94305 USA

[19] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA

[20] NorthShore Univ HealthSyst, Program Personalized Canc Care, Evanston, IL USA

[21] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA

[22] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2017年 / 109卷 / 08期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; VARIANTS; 8Q24;

D O I：

10.1093/jnci/djx084

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 x 10(-12); 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 x 10(-10)). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is amissense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

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页数：5

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