RTK/ERK pathway under natural selection associated with prostate cancer.
Prostate cancer (PCa) is a global disease causing large numbers of deaths every year. Recent studies have indicated the RTK/ERK pathway might be a key pathway in the development of PCa. However, the exact association and evolution-based mechanism remain unclear. This study was conducted by combining genotypic and phenotypic data from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) with related databases such as the HapMap Project and Genevar. In this analysis, expression of quantitative trait loci (eQTLs) analysis, natural selection and gene-based pathway analysis were involved. The pathway analysis confirmed the positive relationship between PCa risk and several key genes. In addition, combined with the natural selection, it seems that 4 genes (EGFR, ERBB2, PTK2, and RAF1) with five SNPs (rs11238349, rs17172438, rs984654, rs11773818, and rs17172432) especially rs17172432, might be pivotal factors in the development of PCa. The results indicate that the RTK/ERK pathway under natural selection is a key link in PCa risk. The joint effect of the genes and loci with positive selection might be one reason for the development of PCa. Dealing with all the factors simultaneously might give insight into prevention and aid in predicting the success of potential therapies for PCa.
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.
Yang
Y
Chen
Xianxiang
X
Xin
Jie
J
Li
Jianfeng
J
Xu
Xiaoxiang
X
Yu
Tianyu
T
Li
Zengnan
Z
Mo
Yanling
Y
Hu
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D030541:Databases, Genetic; D066246:ErbB Receptors / Q000235:genetics*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D040641:Quantitative Trait Loci; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors
D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; D019908:Proto-Oncogene Proteins c-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C496050:PTK2 protein, human