Evaluating genetic risk for prostate cancer among Japanese and Latinos
Cette étude d'association sur le génome entier analyse, chez deux populations distinctes américaines, originaires du Japon (1 033 cas et 1 042 témoins) et d'Amérique latine (1 043 cas et 1 057 témoins), les polymorphismes à simple nucléotide impliqués dans le risque de cancer de la prostate
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. Significant associations from stage 1 (P < 1.0x10-4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/3,748). Results:No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10-6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01x10-5 and stage 2: OR=1.58; P =3.05x10-7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in stage 1 Japanese and Latinos, respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71x10-25 and OR=1.07; P = 1.02x10-16 for Japanese and Latinos, respectively). Conclusions and Impact: Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos.