Polymorphism Of Caspase3 Associated With The Risk And Efficacy Of Lung Cancer

Objective: Aspartate-specific cysteine protease digestion(cysteinyl aspartate-specific proteinases, Caspase) family apoptotic cascade is essential in the process of signal transduction.Caspase3,the core of the implementation process of apoptosis,which is a critical step and all common pathway of apoptosis signaling.Some research have shown that Caspase3 gene polymorphism is responsible for hematological malignancies, gastric cancer, liver cancer, lung cancer.But with the deepening studies of the gene non-coding region, and small non-coding RNA(Micro RNA) plays an important role in the development of tumors.Thus, the relationship between mi RNA polymorphism with cancer has become a hot.Platinum-based combination chemotherapy is the cornerstone of the treatment of advanced non-small cell lung cancer by inhibiting replication of DNA and further inhibiting cell division to induce cells apoptosis. But the drug susceptibility of different patients often have significant differences and the genetic differences between individuals are the main factors of individual differences.Therefore, we hypothesized that one mi RNA(mir-181)SNP site(rs1049216 C>T) of Caspase3 3'UTR maybe associate with the risk of lung cancer of northern Chinese Han population and the efficacy sensitivity of advanced NSCLC of platinum-based combination chemotherapy,providing a theoretical basis for the pathogenesis and individualized treatment of lung cancer.Methods: This article uses the method of case-control study.The case group selected 214 lung cancer patients in the fourth Hospital of Hebei Medical University,Department of Respiratory Medicine and Thoracic Surgery of hospitalization,and all of them were confirmed by the tissue or cell with pathologically.Before chemotherapy fasting,their blood and detailed records of basic patient information are collected.At the same time,the control group were 110 cases in our hospital healthy people, excepting extrapulmonary and lung cancer through imaging and no family history of genetic disease.Using proteinase K-salting method to extract genomic DNA, polymerase chain reaction-restriction fragment length polymorphism(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP) method to detect the distribution of various genotypes of polymorphism of Caspase3 3'UTR rs1049216 C>T.Using RECIST evaluated the solid tumor effect of chemotherapy of 118 patients, platinum-based combination chemotherapy.Result: 1 In the cases and normal control group, the smoking rate was 54.2% and 40.0%, respectively, compared to the two groups were significantly different,P =0.02. After age and sex-adjusted, OR=2.47(95% CI = 1.46-4.21), suggesting that smoking significantly increased the risk of lung cancer. 2 The frequencies of the Caspase3 3'UTR rs1049216 C>T(C/C,C/T,T/T) genetypes among case group were 44.4%, 42.5%, 13.1%, whereas controls were 47.3%, 35.5%, 17.2%, the two groups showed no significant difference(P=0.38);the frequency of C?T alleles of the Caspase3 3'UTR rs1049216 C>T in cases was no different from that in healthy controls(P=0.87).After age, sex, smoking status corrected,compared with C/C genotype reference,C/T genotype and T/T genotype OR values were 1.20(0.71-2.00)and 0.73(0.37-1.45), and independent of the overall risk of lung cancer.Stratified according to smoking status, C/T genotype and T/T genotype does not change the risk of lung cancer among smokers and non-smokers, P values were P= 0.34,OR=1.46(0.68-3.16),P=0.98,OR=0.98(0.37-2.62)and,P=0.73,OR=1.13(0.57-2.22),P= 0.30,OR=0.60(0.23-1.58). 3 Depending on the type of lung cancer hierarchical display: After sex, age and smoking status corrected in C/C as a reference, T allele(C/T + T/T) does not change adenocarcinoma and small cell lung cancer risk, P values were P=0.94, OR0.98(0.58-1.66), P=0.66, OR0.86(0.44-1.69).But the T allele(C/T + T/T) might increase the risk of squamous cell carcinoma of the lung P = 0.04, OR 2.24(95% CI = 1.04-4.83).4 According to first-line platinum-containing chemotherapy of two drugs were divided into effective group and ineffective group, genotype frequencies between the two groups found no significant difference,corrected to C/C type as a reference, T allele(C/T +T/T) does not change the effect of chemotherapy, P=0.11.Conclusion: 1 Smoking increases the risk of lung cancer. 2 Caspase3 3'UTR rs1049216 C>T polymorphism has nothing to do with genetic susceptibility to lung cancer among northern Chinese Han population. And stratified analysis did not find that the relationship beween the polymorphic loci and smokers or non-smoking with lung cancer. 3 Depending on the type of pathology stratified analysis, Caspase3 3'UTR rs1049216 C>T polymorphism does not increase the risk of adenocarcinoma and small cell lung cancer. However, in patients with squamous cell carcinoma of the T allele(C/T + T/T) might increase the risk of squamous cell carcinoma of the lung. 4 The Caspase3 rs1049216 C>T polymorphism were irrelevant with chemotherapy sensitive of advanced non-small cell containing platinum with a two-drug combination.