Evaluating Genetic Risk for Prostate Cancer among Japanese and Latinos

被引：41

作者：

Cheng, Iona ^{[1
]}

Chen, Gary K. ^{[2
]}

Nakagawa, Hidewaki ^{[5
]}

He, Jing ^{[2
]}

Wan, Peggy ^{[2
]}

Laurie, Cathy C. ^{[3
]}

Shen, Jess ^{[3
]}

Sheng, Xin ^{[2
]}

Pooler, Loreall C. ^{[2
]}

Crenshaw, Andrew T. ^{[4
]}

Mirel, Daniel B. ^{[4
]}

Takahashi, Atsushi ^{[6
]}

Kubo, Michiaki ^{[8
]}

Nakamura, Yusuke ^{[7
]}

Al Olama, Ali Amin ^{[9
]}

Benlloch, Sara ^{[9
]}

Donovan, Jenny L. ^{[9
]}

Guy, Michelle ^{[13
]}

Hamdy, Freddie C. ^{[11
]}

Kote-Jarai, Zsofia ^{[13
]}

Neal, David E. ^{[10
]}

Wilkens, Lynne R. ^{[1
]}

Monroe, Kristine R. ^{[2
]}

Stram, Daniel O. ^{[2
]}

Muir, Kenneth ^{[12
]}

Eeles, Rosalind A. ^{[13
,14
,15
]}

Easton, Douglas F. ^{[9
,10
]}

Kolonel, Laurence N. ^{[1
]}

Henderson, Brian E. ^{[2
]}

Le Marchand, Loic ^{[1
]}

Haiman, Christopher A. ^{[2
]}

机构：

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

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

[3] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[4] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

[5] RIKEN, Lab Biomarker Dev, Ctr Genome Med, Tokyo, Japan

[6] RIKEN, Lab Stat Anal, Ctr Genome Med, Tokyo, Japan

[7] Univ Tokyo, Inst Med Sci, Mol Med Lab, Ctr Human Genome, Tokyo, Japan

[8] RIKEN, Ctr Genome Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[9] Strangeways Lab, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Worts Causeway, England

[10] Univ Cambridge, Dept Oncol, Cambridge, England

[11] John Radcliffe Hosp, Nuffield Dept Surg Sci, Oxford OX3 9DU, England

[12] Univ Warwick, Coventry CV4 7AL, W Midlands, England

[13] Inst Canc Res, Oncogenet Team, Div Canc Genet & Epidemiol, Surrey, England

[14] Royal Marsden NHS Fdn Trust, Canc Genet Unit, London, England

[15] Royal Marsden NHS Fdn Trust, Canc Genet Unit, Surrey, England

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2012年 / 21卷 / 11期

基金：

英国医学研究理事会; 日本学术振兴会;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; SEQUENCE VARIANTS; CHROMOSOME; 8Q24; MULTIPLE LOCI; REPLICATION; POPULATION; MEN; BREAST; IDENTIFICATION;

D O I：

10.1158/1055-9965.EPI-12-0598

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods: Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 x 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). Results: No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P < 8.0 x 10(-6)) at chromosome 203; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR = 1.45; P = 7.01 x 10(-5) and stage II: OR = 1.58; P = 3.05 x 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage l), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 x 10(-25) and OR = 1.07; P = 1.02 x 10(-16) for Japanese and Latinos, respectively). Conclusion and Impact: Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. Cancer Epidemiol Biomarkers Prev; 21(11); 2048-58. (C)2012 AACR.

引用

页码：2048 / 2058

页数：11

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