| ObjectivePancreatic cancer is currently one of the worst malignant tumors, the mortality and morbidity close0.99:1. Despite a lot of advancement have been obtained at surgery, radiotherapy, chemotherapy and have improved the survival and quality of pancreatic cancer, but in the past25years, the5-year survival rate is only rising from3%to4%. Currently, surgery is still the most effective treatment of pancreatic cancer. However, due to pancreatic cancer progress insidiously, develop rapidly, invade to the surrounding area early, and the lack of early diagnosis methods, thus more than80%of patients is already advanced and lost the surgery opportunity when they have gone to hospital. Gemcitabine chemotherapy combined another therapy is the main treatment for advanced pancreatic cancer. But its effect is still not satisfactory. So, it’s a reasonable choice to select the appropriate individualized drugs for patients, and it will improve the efficiency of chemotherapy and the quality of life by detecting related genes. Ribonucleotide reductase (RR) is the rate-limiting enzyme in the DNA synthesis pathway, and it has two subunits which are RRM1and RRM2. RRM1is the main target of gemcitabine, and have a great impact on chemotherapy. In recent years, several studies have shown that the activity of RRM1gene and the levels of its expression have close relations to the efficacy and side effects of gemcitabine. This study was designed to investigate the susceptibility factors which will affect the effectiveness of gemcitabine chemotherapy in the patients with advanced pancreatic cancer. And provide new ways and target for individualized treatment of patients with pancreatic cancer.Methods1. The collection of samples and clinical date. A hospital-based case-control study was conducted in Tianjin Medical University Cancer Hospital and Institute (TMUCIH) from January,2010to December,2011. A total of175patients who have been pathologically confirmed enrolled in this study. We have collected the medical records of patients using the epidemiological methods, and follow-up the patients when they have discharged from the hospital.2. Genomic DNA extraction, amplification and genotyping. Fasting blood samples were obtained from pancreatic cancer patients and using heparin to anticoagulated. Genomic DNA was extracted using the adsorption method of Chelex100. The RRM1(-)524T>C、RRM1(-)37C>A、RRM1(-)27CA and RRM133A>G SNPs in the gene of RRM1were detected by polymerase chain reaction (PCR). DNA fragments were sequenced in the company.3. Statistics All the experimental data are used SPSS17.0software for statistical analysis. Measurement data represented by X±S. Overall survival (OS) and progression-free survival (PFS) in univariate analysis using Kaplan-Meier method. Multivariate analysis was used Cox analysis test. The differences between genotyping and toxicity were evaluated by Chi-square test and Fisher’s exact tests. With p<0.05was considered statistically significant.Results The patients of pancreatic ductal adenocarcinoma who have the RRM1(-)524CT/CC or RRM133AG/GG gene type have the better chemosensitivity than other patients, and the more gene type the patients have the better chemosensitivity they have been. The patients who have RRM133A>G and RRM1(-)27C>A polymorphisms have the more incidence of severe neutropenia.Conclusion In conclusion, RRM1gene polymorphisms are closely related to the efficacy and toxicity of gemcitabine chemotherapy in the patients with advanced pancreatic cancer. This result will provide a new way for individualized treatment and a new potential target for the treatment of pancreatic cancer. |
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