The Relationship Between DOK5Gene Polymorphism And Different Treatment With The Survival Of Advanced Esophageal Cancer

1Background and ObjectiveChina is the high incidence of esophageal cancer in the world and also the high-mortality country. More than95%patients are in advanced stage in clinical treatment for the first time. The radically therapeutic method of esophageal carcinoma lies in early diagnosis and early treatment. Surgical procedure still plays a leading role in the treatment of esophageal carcinoma. In recent years, comprehensive treatment has gradually gone into the sight of doctors, radiotherapy, chemotherapy, interventional therapy and so on. Generally, doctors will formulate the scientific and reasonable treatment programs to obtain a better prognosis, according to the general condition and the clinical indicators of patients. However, treatment of advanced esophageal cancer was not identical, the appraisal of treatment effect was not exactly, article on the relationship between different treatment and prognosis of advanced esophageal cancer has a significant difference. This article aims to dissert the relationship between different treatment and clinical indicators with the prognosis of esophageal carcinoma, also investigate the efficacy of different kinds of treatments and optimize treatment strategies.Traditionally, the acquired factors accounted for the major role. But we believed that sensitivity of radiotherapy and resistances of chemotherapy were very important when patients chose the treatment strategies. In our laboratory, using genome-wide association analysis (Genome-wide Associate Study, GWAS) have found the variation of the SNP (Single nucleotide polymorphisms, SNP) rs6023640located at DOK5gene is highly correlated with susceptibility of esophageal cancer, while we conducted a comprehensive analysis of this SNP and different treatment at the same time, and recognized the molecular changes of sensitivity of radiotherapy and resistances of chemotherapy to achieve individualized treatment.2Materials and Method2.1Patient2.1.1Treatments and prognosisWe chose4,475patients successfully followed-up with specific record of treatment strategy from1975to2011. Of all the4,475cases, there were2,793males with a mean age of60.38±8.625, and1,682females with a mean age of61.30±8.895. The proportion of male to female was1.66:1, and the ages are ranging from31to95. The4,475cases were mainly from the Taihang Mountains esophageal cancer high incidence on the junction of Henan, Shanxi, Hebei provinces.2.1.2Treatment and rs6023640SNP in DOK5geneOf the345cases, there were132females and213males. In all cases, there were245patients with radiotherapy alone and100patients with chemotherapy alone. The percentage of male to female was1.61:1. The maximum age was86and the minimum age was33. The median age was61and the average ages were61.83±8.94years. The patients were mainly from the hospitals, including those in Shandong, Shanxi, Beijing, Henan, Anhui and other provinces and cities, starting at the end of2008and ending at the end of2009. All these cases were attending the GWAS, and were conformed through pathology examination by two gastroenterologists and were diagnosed through gastro copy by at least two pathologists.2.2Statistical methodsSeveral elements that can influence treatments or prognosis were chosen. Our team measured18SNP loci genotypes by the GWAS and these related dates were accurately quantified and assigned. The life time was counted in months; the relationship between the individual factor and treatment or the SNP was researched by Chi-square test; affect of the individual and genetic on the prognosis of advanced esophageal carcinoma was researched by the Kaplan-Meier survival curves and its statistically significant difference was checked by Log-Rank test; Cox proportional hazard model in multivariate analysis was applied to eliminate the mutual interactions of multiple variables, and significant risk factors to survival time of advanced esophageal carcinoma were filtered out.3Results3.1Relationship between the three treatments stagey and the clinical pathological date3.1.1Relationship between treatment and clinical indicators of each single factorChi-square test result displayed that there had no significant difference (P>0.05) between male and female in three treatments, there were significant difference (P>0.05) between different age groups in radiotherapy combined with (or) chemotherapy. There were significant differences (P<0.05) of different TNM staging and of lymph node metastasis in two groups of surgery patients.3.1.2Relationship between the groups with different treatment and the survivalGroups were in accordance with surgery and not surgery, the median survival time by132months,50months (P<0.05), using the Kaplan-Meier survival curves and Log-Rank test.Groups were in accordance with radiotherapy alone, chemotherapy alone, radiotherapy combined with chemotherapy, the median survival time by48months,35months,54months (P>0.05), the Kaplan-Meier survival curves and Log-Rank test were used.3.1.3TNM staging grouping, relationship between the groups with different treatment and the survivalAccording to different TNM staging, II staging in accordance with surgery alone, surgery combined with radiotherapy and (or) chemotherapy, the median survival time by132months,154months. The Kaplan-Meier survival curves were drew and the entirety has no statistically difference (P>0.05) tested by Log-Rank test.Ⅲ staging in accordance with surgery alone, surgery combined with radiotherapy and (or) chemotherapy, the median survival time by60months, 62months. The Kaplan-Meier survival curves were drew and the entirety has no statistically difference (P>0.05) tested by Log-Rank test.3.1.4Lymph node metastasis grouping, relationship between the groups with different treatments and the survivalAccording to lymph node metastasis, positive patients in accordance with surgery alone, surgery combined with radiotherapy and (or) chemotherapy, the median survival time by111months,89months. The Kaplan-Meier survival curves were drew and the entirety has no statistically difference (P>0.05) tested by Log-Rank test.Negative patients in accordance with surgery alone, surgery combined with radiotherapy and (or) chemotherapy, the median survival time by135months,172months. The Kaplan-Meier survival curves were drew and the entirety has no statistically difference (P>0.05) tested by Log-Rank test.3.1.5Survival affected analysis on advanced esophageal carcinoma of individual independent factor and comprehensive factorsWe picket out independent risk factors analyzing the multivariate Cox proportional hazards model. The consequence showed that lymph node metastasis, age, sex and treatment were independent factors affecting the prognosis of patients with advanced esophageal carcinoma. For overall patients, the results showed that lymph node without metastasis, younger age, female were protective factors on prognosis (P<0.01).3.2Analysis of three treatments, SNP and other clinic pathological date3.2.1Relevance between treatment and SNPThe Chi-square test was used to analyze genotyping with two different treatment (radiotherapy alone and chemotherapy alone) of all the sites which had been done, the outcome showed that the genotype of rs6023640locus in DOK5was related to treatment (P<0.01).3.2.2Relationship between rs6023640locus within DOK5gene and prognosisRadiotherapy alone, there were199cases of GG type,46cases of TG and TT type. The Kaplan-Meier survival curves were drew and the entirety has statistically difference tested by Log-Rank test (x2=4.459, P<0.05)Chemotherapy alone, there were55cases of GG type,45cases of TG and TT type. The Kaplan-Meier survival curves were drew and the entirety has statistically difference tested by Log-Rank test (x2=6.650, P<0.05)4Conclusions4.1Surgery combined with radiotherapy and (or) chemotherapy compared with surgery alone does not prolong survival of patients with advanced esophageal carcinoma;4.2Sex, age, lymph node metastasis and treatment are important factors affected the survival of advanced esophageal cancer;4.3The polymorphic variation of rs6023640locus within DOK5gene was significantly related to treatment. TG/TT type was sensitive to radiotherapy and chemotherapy.