Caspase3 Gene Promoter Region Rs12108497 A/G Polymorphism Associated With Risk And Efficacy Of Lung Cancer

Objective:The incidence and mortality of lung cancer ranks the first in the world.Abnormal apoptosis can lead to malignant tumors occurrence.Caspase gene plays a crucial role in regulating apoptosis.Caspase3 is the final executor of apoptosis reaction.Domestic and foreign studies have shown that Caspase3 single nucleotide polymorphism(single nucleotide polymorphism,SNP)is associated with malignant tumor’s occurrence and curative effect.Platinum can inhibit DNA synthesis and induce cell apoptosis.Patinum-based chemotherapy has become the prior choice for lung cancer chemotherapy,but usually different patients have remarkable difference in the efficacy of platinum-based combination chemotherapy.Individual differences in medication are often associated with genetic factors.At present,there are few studies on the Caspase3 promoter region polymorphism association with tumor susceptibility and treatment efficacy.This study was designed to investigate the association between Caspase3 rs12108497 A/G single nucleotide polymorphism and the risk of lung cancer and the efficacy of late stage NSCLC standard platinum-based combination chemotherapy efficacy.Methods:Peripheral blood samples and clinical data has been collected from the people who has been diagnosed lung cancer by pathologic methods(203patients)and the healthy people(106 controls).Using proteinase K-salting method to extract genomic DNA,Using PCR-RFLP(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)method detect Caspase3 rs12108497 SNP.Using RECIST standard evaluation the efficacy of the patients with platinum-based combination chemotherapy.All data were analyzed by SPSS 21.0 software,and it was considered that P<0.05 was statistically significant.Result:1 In the cases group smokers account for 57.6%,in the control group smokers account for 43.4%.Two groups have significant statistical differences(P = 0.017),adjusted age,gender calculate OR=2.479(95%CI=1.210-5.082)indicating that smoking is a risk factor for lung cancer.2 The frequencies of the Caspase3 promoter region rs12108497 A/G(AA AG GG)in the cases group are 49.8%,44.3%,5.9%.In the controls group are39.6%,48.1%,12.3%,the genotype distribution between the two groups have no statistical differences(P=0.073).The frequency of G allele in the case group VS in the control group is 28.1%VS36.3%.G alleles distribution has statistical difference in the the two groups(P=0.035).After sex,age and smoking status adjusted,OR= 0.679(95%CI=0.465-0.991),indicating that G allele can decrease the risk of lung cancer.After adjusting for gender,age,smoking status,AA genotype as the reference,OR of AG genotype is0.776(95%CI=0.467-1.289,P=0.22),GG genotype OR is 0.395(95%CI=0.163-0.958,P=0.026),indicating GG genotype compared with AA geneotype can reduce the risk of lung cancer.According to smoking status,as AA genotype for a reference,in the smokers,AG genotype calculate OR=0.804(95%CI=0.395-1.636,P=0.445),GG genotype calculate OR=0.388,(95%CI=0.106-1.420,P=0.186).In the none smokers,AG genotype calculate OR=0.749,(95%CI=0.360-1.560,P=0.413),GG genotype calculate OR=0.382,(95%CI=0.114-1.279,P=0.256).It is not found that the relationship between Caspase3 rs12108497 A/G and the risk of lung cancer in the smokers or in the none smokers.3 According to the type of lung cancer hierarchical illustrate: It is no correlation between Caspase3 rs12108497 A/G polymorphism and the risk of adenocarcinoma,squamous cell carcinoma and small cell carcinoma.AA genotype as a reference,P value respectively is 0.189;0.086;0.556;Adjusted sex,age and smoking status OR(95%CI)respectively is:0.748(0.157-3.569);0.911(0.187-4.45);0.612(0.120-3.118).4 Case group has been excepted surgery radiotherapy molecular targeteddrugs and give up treatment,totally 88 non-small cell lung cancer patients received first-line platinum-containing chemotherapy.According to RECIST(Response Evaluation Criteria In Solid Tumor,RECIST)to evaluate the efficacy.CR,PR,SD are divided into effective group,PD is divided into ineffective group.Genotype distribution not be found significant difference in the two groups.There is no significant difference between GG+AG genotype and AA genotype(P=0.782).Hierarchical According to the type of lung cancer hierarchical :It was no significant correlation between Caspase3 rs12108497A/G polymorphism and the efficacy of adenocarcinoma,squamous cell carcinoma with platinum-based chemotherapy(P=0.805;P=0.376).Conclusion:1 Smoking significantly increases the risk of lung cancer.2 Caspase3 rs12108497 G allele decreases the risk of lung cancer.3 Compared with Caspase3 rs12108497 AA genotype,GG genotype is a protective factor for lung cancer,AG genotype does not change the risk of lung cancer.4 Smokers or non-smokers with lung cancer are not be found the relationship between Caspase3 rs12108497A/G polymorphism and correlation between the risk of lung cancer.5 According the type of lung cancer hierarchical Caspase3rs12108497A/G polymorphism can not increase the risk of adenocarcinoma,squamous cell carcinoma and small cell carcinoma.6 Caspase3 rs12108497A/G polymorphism not associate with the efficacy of NSCLC by platinum-based chemotherapy.According to the type of NSCLC hierarchical,Caspase3 rs12108497A/G polymorphism are not correlated with the efficacy of adenocarcinoma,squamous cell carcinoma and small cell carcinoma by advanced platinum with a two-drug combination chemotherapy.