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 × 10-16for 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.
Written by:
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. Are you the author?
University of Hawaii Cancer Center, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813.
Reference: Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2048-58.
doi: 10.1158/1055-9965.EPI-12-0598
PubMed Abstract
PMID: 22923026
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