Association Of Snp In ERCC1 Gene With Sensitivity And Adverse Reactions To Chemotherapy In Patients With Small Cell Lung Cancer

Objective:To investigate the relationship between single nucleotide polymorphism of ERCC1 gene C118 T and short-term curative effect and adverse reaction to chemotherapy in patients with small cell lung cancer. To understand the causes of adverse reactions caused by individual differences in short-term curative effect and patients after chemotherapy.Methods:(1) Research data collection:42 cases were treated in the Department of internal medicine the Second Affiliated Hospital of Dalian Medical University, were confirmed by pathology, diagnosis of small cell lung cancer, expected survival for at least 3 months, is expected to be tolerated at least 4 cycles of chemotherapy, and approved by the ethics committee, and all patients signed informed consent.(2) Chemotherapy curative effect evaluation were according to the 1.1 criteria in solid tumors(Response Evaluation version Criteria in Solid Tumors, RECIST v1.1), 2cycles, curative effect Evaluation of 2 and 4 cycle time is 3 weeks after chemotherapy,21 days for a cycle of chemotherapy. Adverse reactions evaluation were according to the National Cancer Institute(NCI) of Common Adverse event evaluation standard version4.0(CTCAE v4.0) in 2009.(3) Test method: collecting peripheral blood cells in patients with SCLC, genome DNA was extracted, further to C118 T single nucleotide polymorphism in ERCC1 gene by polymerase chain reaction(PCR), the PCR products were detected by using thesecond generation high-throughput gene sequencing line.(4) Statistical methods:Data analysis was performed using Statistical Package for Social Sciences(SPSS 20.0 software).The observed genotype frequencies of the ERCC1C118 T polymorphisms and clinical characteristics was assessed using the chi square test,odds ratio and 95% CIs.All statistics were two-sided,and a P-value<0.05 was considered statistically significant.Results:(1) DNA extraction result: 42 cases of small cell lung carcinoma patients can be extracted DNA, but because the whole blood samples retained in different stages and individual differences in patients, the different concentration of DNA extraction,there was no significant difference in the overall.(2) PCR product electrophoresis results:According to the reaction conditions of PCR,we can smoothly obtain PCR products, a few PCR products were also obtained after fine-tuning the reaction conditions. PCR products and DNA electrophoresis results compared to Marker and that PCR product is the desired product, the electrophoretic bands appear unequally, but had no effect on gene sequencing.(3) PCR products were sequenced: The Shanghai Biological company uses second-generation sequencing methods sequencing, sequencing results obtained by the analysis: 42 patients with small cell lung cancer patients, the frequency of occurrence of a base C 72.6%, accounting for T base 27.4 %. CC homozygous wild-type genotype accounted for 47.6%, heterozygous genotype CT type accounted for 50%, homozygous genotype TT 2.4%. 70.6% of young(≤60 years) small cell lung cancer patients showed CC genotype, age(>60 years) patients showed T-containing genotypes accounted68.0%.the result was no statistically significant in sex, initial blood NSE levels and stages.(4) The C118 T loci SNP of ERCC1 gene were statistically significant in terms of recent chemotherapy in Small cell lung cancer, while no significant difference in gastrointestinal adverse reactions and bone marrow suppression.Conclusion:(1) Primary diagnosis of small cell lung cancer patients, younger(≤60years) patients with the C118 T loci polymorphism of ERCC1 gene more performancefor the CC genotype, elderly patients(> 60 years) showed more T-containing genotypes.(2) The C118 T loci polymorphism of ERCC1 gene showed CC genotype higher sensitivity to hemotherapy containing T genotype in patients with small Cell Lung,which can be used as a biological markers when we evaluate the therapeutic effect to chemotherapy.(3) There are no correlation between the C118 T loci polymorphism of ERCC1 gene and upper gastrointestinal adverse reactions and bone marrow suppression in patients with small cell lung cancer.