ABSTRACT
Base excision repair (BER) plays an important role in maintaining genome integrity and anti-cancer drug resistance. Single nu-cleotide polymorphisms (SNPs) in BER genes were detected in 500 lung cancer patients and 500 cancer-free controls. A logistic regression model was applied to analyze the relationship between lung cancer susceptibility and BER SNPs coupled with a wide range of epidemiological factors in a Chinese population. SNPs including rs25487 in the X-ray repair cross-complementing group 1 gene, rs1052133 in the 8-oxoguanine DNA gly-cosylase gene, and rs1136410 in the poly (ADP-ribose) polymerase 1 gene were identified. Multivariate analysis showed that the rs25487-AG geno-type was associated with a higher incidence of lung cancer compared with the GG genotype. The rs25487 SNP was associated with the pathological distribution of lung cancer. Moreover, rs1052133-GG was associated with early age of lung cancer onset compared with the CC genotype. Our data demonstrated that the SNPs rs25487 and rs1052133 are risk factors for lung cancer in epidemiologically susceptible Chinese people.
Subject(s)
Asian People/genetics , DNA-Binding Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Case-Control Studies , China/epidemiology , Comorbidity , DNA Glycosylases/genetics , Female , Genotype , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Odds Ratio , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases/genetics , Risk Factors , X-ray Repair Cross Complementing Protein 1 , Young AdultABSTRACT
Prostate cancer cells were transfected with plasmids [empty plasmids, wild-type pcDNA3.1-p53 (V/V), mutant type pcDNA3.1- p53 (G/G)] to analyze the effect of p53 gene polymorphisms on the proliferation, cycle, and apoptosis of prostatic cancer cells. Empty plasmids containing wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1- p53 (G/G) were used to transfect PC3 and LNCaP cells, respectively. Cell proliferation was detected at 0, 24, 48, and 72 h using the MTT method. Cells were collected at 24 and 72 h. The distribution of cell cycles in various groups was detected using flow cytometry (propidium iodide staining method) and the apoptosis rate was detected using annexin V + propidium iodide double staining. Compared with the control group, wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G) showed a significant inhibitory effect on cell proliferation (P < 0.05); the inhibitory effect of the mutant type was stronger than that of the wild-type. There was no significant difference between PC3 cells and LNCaP cells. After transfection with wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1-p53 (G/G), PC3 and LNCaP cells were arrested in the G0/G1 stage. Transfection with pcDNA3.1-p53 (G/G) showed a more significant effect than transfection with pcDNA3.1-p53 (V/V). Both the wild-type pcDNA3.1-p53 (V/V) and mutant-type pcDNA3.1-p53 (G/G) led to an increased apoptosis rate of PC3 and LNCaP cells. The p53 gene polymorphism affects the proliferation, apoptosis, and cycle of prostate cancer cells and may serve as a reliable index for the diagnosis and treatment of prostate cancer.