title: Genome-wide haplotype association study identifies BLM as a risk gene for prostate cancer in Chinese population.
abstract: Prostate cancer (PC) is a common malignant tumor that occurs in the prostate epithelial cells. It is generally considered to be caused by both genetic and environmental factors. To identify the genetic risk factors of PC in Chinese population, we carried out a genome-wide haplotype-based association study. The 33 Chinese PC cases were from the public GEO database (GSE18333), and the 139 Chinese controls (CHB) were from the HapMap project. Our analysis included three stages: (1) identifying the linkage disequilibrium (LD) blocks and performing genome-wide haplotype association scan, (2) mapping PC-risk haplotypes to PC candidate genes, and (3) prioritizing PC candidate genes based on their similarity to known PC susceptibility genes. The results showed that (1) 749 haplotypes were significantly associated with PC (P < 1E-5). (2) Then, we mapped these significant haplotypes to genes and got 454 PC candidate genes. (3) After prioritizing the candidate genes based on their similarity to known PC susceptibility genes, we found that seven novel PC susceptibility genes including BLM, RPS6KA2, FRK, ERBB4, RBL1, PAK7, and ERBB2IP. Among the seven genes, BLM gene ranked first (P = 1.89E-04). A haplotype GGTTACCCCTC (rs2270131, rs2073919, rs11073953, rs12592875, rs16944863, rs2238337, rs414634, rs401549, rs17183344, rs16944884, and rs16944888) on chromosome 15q26.1 had significant association with PC (P = 2.37E-11). To our knowledge, this is the first genetic association study to show the significant association between BLM gene and PC susceptibility in Chinese population.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongchao
authors.initials: H
authors.lastname: Lv
authors.forename: Wenhua
authors.initials: W
authors.lastname: Lv
authors.forename: Miao
authors.initials: M
authors.lastname: Shi
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.forename: Meiwei
authors.initials: M
authors.lastname: Luan
authors.forename: Hongjie
authors.initials: H
authors.lastname: Zhu
authors.forename: Ruijie
authors.initials: R
authors.lastname: Zhang
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D044466:Asian People; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D053484:RecQ Helicases / Q000235:genetics*
chemical_list: C097151:Bloom syndrome protein; D053484:RecQ Helicases