title: The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: a pooled analysis of 41 sets of data from case-control studies.
abstract: Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR=0.92, 95%CI=0.852-0.994, P=0.034; I(2)=0%, P=0.042; allele analysis: pooled OR=0.915, 95%CI=0.874-0.958, P=0; I(2)=0%, P=0.424; codominant model: OR=0.835, 95%CI=0.762-0.916, P=0; I(2)=0%, P=0.684) and rs1570360/VEGF (recessive model: OR=0.596, 95%CI=0.421-0.843, P=0.003; I(2)=23.9%, P=0.269; codominant model: OR=0.576, 95%CI=0.404-0.820, P=0.002; I(2)=49.1%, P=0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR=0.834, 95%CI=0.769-0.904, P=0; allele analysis: OR=0.908, 95%CI=0.863-0.955, P=0; AA vs CC: OR=0.829, 95%CI=0.750-0.916, P=0; AC vs CC: OR=0.837, 95%CI=0.768-0.912, P=0). In addition, in Asians (allele analysis: OR=0.21, 95%CI=0.168-0.262, P=0) and Caucasians (recessive model: OR=0.453, 95%CI: 0.240-0.855, P=0.015; codominant model: OR=0.464, 95%CI=0.240-0.898, P=0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa.
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Institute of Urology and Nephrology, the People's Liberation Army 303 Hospital of Guangxi, Guangxi Zhuang Autonomous Region, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China; Fudan Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Institute of Cardiovascular Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Jianling
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Information center, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Luo
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: zengnanmo@hotmail.com.
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China; Medical Research Center, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: ylhupost@163.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics*
keywords: B-cell CLL/lymphoma 2; BCL2; BPH; CCND1; CI; CNKI; China National Knowledge Infrastructure; ChinaPCa; Chinese Consortium for Prostate Cancer Genetics; EGF; EGFR; ERK; GSEA; GWAS; HWE; Hardy–Weinberg equilibrium; IGF1; MAPK; Meta-analysis; OR; PCa; Polymorphism; Prostate cancer; RAF1; RTK; RTK/ERK pathway; VEGF; benign prostatic hyperplasia; confidence interval; cyclin D1; epidermal growth factor; epidermal growth factor receptor; extracellular signal-regulated kinase; gene set enrichment analysis; genome-wide association studies; insulin-like growth factor 1; mitogen-activated protein kinase; odd ratio; prostate cancer; receptor tyrosine kinases; v-raf-1 murine leukemia viral oncogene homolog 1; vascular endothelial growth factor A