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Association Of Genetic Polymorphism In The DNA Repair Gene XRCC1 With Susceptibility Of Lung Cancer In A Non-smoking Female

Posted on:2005-02-06Degree:MasterType:Thesis
Country:ChinaCandidate:M C LiFull Text:PDF
GTID:2144360122491044Subject:Epidemiology and Health Statistics
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ObjectiveXRCC1 polymorphism at Arg399Gln site has been shown to modulate DNA repair capacity, we therefore assessed the relationship between the XRCC1 polymorphism and susceptibility to lung cancer in non - smoking female via a hospital - based , case - control study.MethodsCase were 50 female patients who was diagnosed with lung cancer between January 2003 and January 2004 in China Medical University Hospital and Liaon-ing Tumor Hospital . the histological types of cancer were as follows; 16 squa-mous cell cacinoma. 26 adenocarcinoma, and 8 small cell carcinoma and big cell carcinoma. Controls were selected from patients who was diagnosed with other lung disease in the hospital at the same time . These controls were matched to cases on age( 5 years). Information concerning demographic and relative risk factors were obtained for each case and control by a trained ineterviewer.XRCC1 Genotypes were determined by PCR - RFLP approaches. PCR primers were 5 ' - TTGTGCTTTCTCTGTGTCC - 3 ' 5 ' TCCTCCAGC-CTTTTCTGATA -3' ,which generate a 615bp fragment. PCR reaction mixture (25 l)consisted of 0.5 ~ 1 g of genomic DNA, 20pmol/L of each primer , 2. 5mM deoxynucleotide triphosphate, 2.5 l 10 PCR buffer (Tris -HCLPH8. 3 100mmol/L, KC1 500mmol/L, MgCL,15mmol/L) , and 5 unit of Taq polymer-ase(TaKaRa Biotechnology Co. ,Ltd). PCR program initialed by a 2min denat-uration step at 94C , Mowed by 30 cycles of 94C for 30s, 56C for 30s, 72C for 30s, and a final elongation step of 72 C for 10 min. The PCR products weredigested overnight at 37C. Tbe digestion product was resolved on 2% agarose gel . The homozygous Arg allele is determined by the presence of two bands at377 and 238 bp, the homozygous Gln allele is determined by the presence of theuncut 615bp band , and the heterozygous Arg/Gln allele is determined by the presence of three bands at 615,377, and 238bp.The statistical significance of the differences in the frequencies of XRCC1 codon 399 genotypes between groups was calculated by x test, the adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. All analyses were performed using SPSS for version 11.5.Results DNA repair system are fundamental to the maintenance of genomic integrity in face of replication errors, environmental insults and cumulative effects of age , and their inactivation can dramatically increase individual susceptibility to cancer.XRCC1 is one of DNA repair gene involved in BER pathway. It acts as a facilitator or coordinator in BER, through its interaction with poly ( ADP - ri-bose)polynerase, DNA polymerase ,and DNA ligaseIII. shen et al identified three coding polymorphisms in the XRCC1 gene at the codons 194, 280, and 399. the 399Gln polymorphism resulting from a guanine to adenine nucleotide occurs in the poly ( ADP - ribose) polynerase binding domain and may affect complex assembly or repair efficiency.In our study, All of the subjects were Shenyang non - smoking female. The mean age was similar between cases(59 10.7) and controls(58. 3 10. 1). Cases showed a higher prevalence of oil smoke compared with controls ( p < 0. 05). the OR for lung cancer by oil smoke was 3.27(95%CI 1. 37 ~7. 81).No significant deviation was observed for the distribution of genotypes between cases and controls. When the cases were categorized by histological type , however, the frequencies of Arg/Arg, Arg/Gln Gin/Gin in the adenocacino-ma group(30.8% ,42.3% 26.9% ) were significantly different from those a-mong controls ( 54% ,42% 4% , respectively, p < 0.05 )When the Arg/Arg genotype was used as the reference group, the Gin/Gin genotype was associated with elevated but not statistically significant risk for all lung cancer. ( adjusted OR = 5.43 95% CI 0. 99 ~ 29. 7) When analyses were stratified by histology ,the individual carrying Gin/Gin genotype was at an increased risk for lung adenocarcinoma as compared with those with the Arg/Arg genotype( OR = 14.12 95% CI 2. 14 ~ 92.95 adjusted for age, and oil smoke exposure) ,furth...
Keywords/Search Tags:female lung cancer, XRCCl gene, genetic polymorphism
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