Genetic susceptibility to prostate cancer in Taiwan: A genome‐wide association study

• Published in: Molecular carcinogenesis Vol. 63; no. 4; pp. 617 - 628
• Main Authors: Bau, Da‐Tian, Tsai, Chia‐Wen, Chang, Wen‐Shin, Yang, Jai‐Sing, Liu, Ting‐Yuan, Lu, Hsing‐Fang, Wang, Yu‐Wen, Tsai, Fuu‐Jen
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2024
• Subjects: 8q24.21; Carcinogenesis; Chromosome 15; Chromosome 8; CORO2B; genetic risk score; Genetics; Genomes; genome‐wide association study; GRS; lncRNA; Molecular modelling; Non-coding RNA; Prostate cancer; Single-nucleotide polymorphism; SNP; Taiwan; prostate cancer; lncRNA; SNP; genome-wide association study; GRS; genetic risk score; 8q24.21; CORO2B
• ISSN: 0899-1987; 1098-2744; 1098-2744
• DOI: 10.1002/mc.23676

We conducted the first genome‐wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single‐nucleotide polymorphisms (SNPs) reached genome‐wide significance (p < 5 × 10−8). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36–1.76, p = 5.30 × 10−11; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31–1.51), p = 8.77 × 10−21; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16–1.35), p = 2.14 × 10−8. We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10−43, and rs1456315 (inside PRNCR1), p = 4.33 × 10−42. We confirmed 35 out of 49 GWAS‐identified East Asian PCa susceptibility SNPs. In addition, we identified two SNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver‐operating characteristic curve for the GRS to predict PCa was 0.67 (95% CI, 0.63–0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence.