| Objective: To investigate whether single nucleotide polymorphisms(SNPs) of DNA repair gene excision repair cross-complementation group 1 (ERCC1) and xerodenna pigmentosum group D/excision repair cross-complementation group 2 (XPD/ERCC2)were associated with the sensitivity to platinum-based chemotherapy in advanced non-small-cell lung cancer(NSCLC) patients in Chinese population and to explore the its theoretical evidence to guide cisplatin based individualized chemotherapy for NSCLC patients.Methods: Seventy-eight patient were confirmed with advanced NSCLC pathologically. DNA from peripheral blood was obtained before they were treated with platinum based chemotherapy. Polymorphisms of ERCC1 and XPD were detected by the polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method. Clinical response was evaluated after 2 cycles of chemotherapy.χ2 test was used to analyze the association of polymorphisms of ERCC1, XPD with age,sex, pathology type, staging, smoking status and ECOG performance.The significance of differences in frequencies and genotypes between good and poor responders was calculated using theχ2 test. Fishe's exact test was performed when theoretical frequency had expected count less than1 or n﹤40.The logistic regression model was used to calculate the odds ratios (OR) and their 95% confidence intervals (CI) after corrected factor of age, sex, smoking status and score of ECOG performance .Results: In 78 patients, the range of age was from 29 to 81,mean age(57.50±1.56) years,43(55.1%) patients were older than 60 years, 24 (30.8%) were between (40-60)years, included 60 years.11 (14.1%) were younger than 40 years; There were 52 males(66.7%) and 26 females(33.3%); Thirty-three(42.3%)were squamous cell carcinoma, 42(53.9%)were adenocarcinoma and 3(3.8%) were undifferentiated carcinoma; In Chemothrapy, DP was 11(14.1%),GP was 61(78.2%) and NP was 6(7.7%);Smoking history: 30(38.5%)with no smoking history,48(61.5%) with smoking history;ECOG performance status : 33(42.3%) were 0,40(51.3%)were 1 and 5(6.4%) were 2;Clinical tumor stage:49(62.8%) wereⅢB stage and 29(37.2%) wereⅣstage. Polymorphisms: There were 48(61.5%),28(35.9%) and 2 (2.6%) patient,s ERCC1 C118T genotype as C/C,C/T and T/T respectively, there were 63(80.8%),14(17.9%),1(1.3%) patient,s XPD(Lys751Gln) genotype as Lys/Lys, Lys/Gln and Gln /Gln respectively.No associations were detected between polymorphisms of ERCC1,XPD and age,sex, histologic type,ECOG performance status, smoking history and clinical tumor stage(P﹥0.05). The difference of clinical response was not found between age,sex, ECOG performance status and smoking history(P>0.05).The polymorphic genotypes of ERCC1 (Asn118Asn) were related to chemotherapy sensitivity. Among responders, the allele frequencies of homozygous wild type(C/C) , heterozygous (C/T) , and homozygous variant (T/T) were 7(35.0%),11(55.0%) and 2(10.0%) respectively. The corresponding genotypes in the nonresponders were 41(70.7%), 17(29.3%) and 0(0%) respectively. The difference between the 2 groups was statistically significant (P=0.003).After combining the T/T and C/T genotypes, the difference remained statistically significant (P=0.005). The odds ratio (OR) for responders was 0.223(P=0.005) and the 95% confidence interval (CI) was between 0.076 and 0.657. After using the logistic regression model to correct the factors of age,sex,smoking history and ECOG performance status, OR of clinical response to platinum based chemotherapy. of patients carrying the C allele(C/C) with those who carry at least 1 T allele (T/T+C/T)was 0.128 (P=0.000), 95%CI:0.058-0.286), b=-2.053.Conclusion: Single nucleotide polymorphisms of ERCC1 was associated with sensitivity to platinum-based chemotherapy in advanced NSCLC patients. patients carrying at least 1 T allele (T/T C/T)were more likely to be responders to chemotherapy compared with those who carrying the C allele; suggesting T allele may be a predictor for advanced NSCLC patients who would be sensitive to platinum agents. |
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