Evaluating genetic risk for prostate cancer among Japanese and Latinos.

Cheng I., Chen GK., Nakagawa H., He J., Wan P., Laurie CC., Shen J., Sheng X., Pooler LC., Crenshaw AT., Mirel DB., Takahashi A., Kubo M., Nakamura Y., Al Olama AA., Benlloch S., Donovan JL., Guy M., Hamdy FC., Kote-Jarai Z., Neal DE., Wilkens LR., Monroe KR., Stram DO., Muir K., Eeles RA., Easton DF., Kolonel LN., Henderson BE., Le Marchand L., Haiman CA.

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 × 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 × 10(-6)) at chromosome 2q33; 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 I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 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 I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 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.

DOI

10.1158/1055-9965.EPI-12-0598

Type

Journal article

Publication Date

2012-11-01T00:00:00+00:00

Volume

21

Pages

2048 - 2058

Total pages

10

Keywords

Asian People, California, Cohort Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Hawaii, Hispanic or Latino, Humans, Japan, Male, Models, Statistical, Neoplasm Staging, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk, SEER Program

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