title: Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population.
abstract: The cell cycle governs the proliferation and growth of cells and is strictly controlled by some regulators including cyclins, CDKs and CKIs. Germ-line and somatic mutations in cell cycle genes were frequently observed in a subset of cancers including non-small cell lung cancer (NSCLC). In this study, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in cell cycle genes may contribute to the prognosis of NSCLC in China. 54 potentially functional polymorphisms in key cell cycle genes (CDK1, CDK2, CDK4, CDK6, CDK7, CCND1, CCND2, CCND3, CCNE1, CCNA1, CCNA2, CCNB1, CCNH, p15, p16, p18, p19, p21, p27, Cdc25A and Cdc25B) were genotyped by using Illumina SNP genotyping platform to evaluate their associations with survival of NSCLC in a clinical cohort of 568 patients. We found that p18 rs3176447 variant genotypes were significantly associated with the decreased risk of death of NSCLC patients (adjusted HR=0.74, 95% CI=0.57-0.97 in an additive model; adjusted HR=0.76, 95% CI=0.55-0.97 in a dominant model); however, p21 rs2395655 variant genotypes were significantly associated with the increased risk of death (adjusted HR=1.21, 95% CI=1.02-1.42 in an additive model; adjusted HR=1.38, 95% CI=1.07-1.78 in a recessive model). Furthermore, the combined effect of unfavorable genotypes for these two SNPs was more prominent in patients with squamous cell carcinoma, late stage and without chemo- or radio-therapy. Although the exact biological function remains to be explored, our findings suggest possible association of polymorphisms of p18 and p21 with the prognosis of NSCLC in a Chinese population. Further large and functional studies are needed to confirm our findings.
authors.affiliation: Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
mesh_terms: D044466:Asian People; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D005260:Female; D018816:Genes, cdc; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models
chemical_list: D055511:CCN Intercellular Signaling Proteins; D018844:Cyclin-Dependent Kinases