A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.
Marzec J., Mao X., Li M., Wang M., Feng N., Gou X., Wang G., Sun Z., Xu J., Xu H., Zhang X., Zhao S-C., Ren G., Yu Y., Wu Y., Wu J., Xue Y., Zhou B., Zhang Y., Xu X., Li J., He W., Benlloch S., Ross-Adams H., Chen L., Li J., Hong Y., Kote-Jarai Z., Cui X., Hou J., Guo J., Xu L., Yin C., Zhou Y., Neal DE., Oliver T., Cao G., Zhang Z., Easton DF., Chelala C., PRACTICAL Consortium None., CHIPGECS Group None., Al Olama AA., Eeles RA., Zhang H., Lu Y-J.
Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.