| 1Background and PurposeMost published studies indicate that it is a complex procedure involved in multiple factor, multiple stages for esophageal cancer. In the West, smoking is a certainly risk factor for esophageal cancer, while in China, the conclusion is still controversial. The recent studies suggested that smoking played an important role in this process, and the amount of smoking in a dose-response relationship. Now reports about the relationship between the onset age and age of.smoking initiation, and the correlation between preoperative smoking and patient survival is less investigated, but because of the small sample size, the results exist more controversial. Some studies show that preoperative smoking is an independent prognostic factor for patients with esophageal cancer, and the5-year survival of patients with non-smoking was better than smoking, but the others studies suggest that it had no effect on the prognosis of esophageal cancer. In addition, our research group using the genome-wide association analysis (GWAS) found18SNPs which is closely related to the incidence risk with esophageal cancer, but the relationship with the prognosis survival is unclear. In this study, analysis4330cases of esophageal squamous cell carcinoma of the age of smoking initiation, smoking time, the smoking history and survival, we aim to clarify the relationship between the onset age and age of smoking initiation, and the impact on the survival. Also, analyze the18SNPs of variation to preliminarily study the molecular mechanism of smoking affecting prognosis.2Materials and Methods2.1Patients4330cases diagnosed as esophageal squamous cell carcinoma which has smoking history, clear follow-up records and postoperative pathological in1973to2012, which from Henan Province esophageal biological samples database.25968patients of male median age are60years (34-88y);1734patients of female median age are61years (36-94y).2.2Households survey, Verification hospital data and Follow-upHousehold survey (the contents of the questionnaire include:name, sex, date of birth, age, home address, telephone, hospital treatment, smoking history, family history of malignant tumors and so on) and phone follow-up to record some patient’s basic information and survival, and in accordance with the provided by the patients with treatment of hospital to review, supplement the treatment modalities in patients with and the pathological diagnosis. Follow-up time is from the date of surgery to December8,2012.A11the patients make sure that deaths were exclusively attributed to ESCC.2.3Smoking standardsSmoking:more than one year of continuous smoking≥5cigarettes a day2.4Blood samples, DNA extraction and Taqman genotypingPatient consent, signed informed consent, collecting5ml EDTA anticoagulated peripheral venous blood. Using Flexi Gene DNA extraction kit (Qiagen) to extract the genomic DNA in the blood samples. Using Taqman (?) genotyping technology detects the obvious difference18SNPs with preliminary GWAS work. 2.5Statistical analysisAll data were statistically analyzed using SPSS17.0. Using the Spearman correlation analysis, the Kaplan-Meier methods, Log-rank test the differences, chi-square test and the Cox model statistical methods. Inspection standards:α=0.05.3Results3.1SurvivalIn11,865patients,8914cases have accurate home address and clearly telephone number, successful follow-up is4330patients, follow-up rate is48.6%. This group of patients’5-year survival is52%, and the median survival is67months.3.2The relationship between the onset age and age of smoking initiation and smoking timeThe onset age is highly correlated with the onset age and age of smoking initiation and smoking time (r=0.475, P<0.001), the linear correlation coefficient of0.221.3.3Comparison of survival in patients with smoking and non-smoking2646cases of non-smoking and1684cases of smoking patients have significant differences in prognostic survival, and the survival of former was significantly better than the latter (x2=22.542, P<0.001).1649cases smoking and947cases non-smoking has no significant difference in survival of male patients (x2=1.354, P=0.245).1649male smoking and1699female non-smoking has significant difference in prognosis (x2=37.110, P<0.001).947male non-smoking and1699female non-smoking has significant difference in prognosis (x2=16.884, P<0.001).3.418SNPs Hardy-Weinberg genetic equilibrium testIn2129cases,16SNPs genotyping after by the crowd goodness of fit Hardy-Weinberg equilibrium test observed and predicted values goodness of fit are good (P=0.42), except rs614125(x2=19.763, P<0.001) and rs283856(x2=5.970, P=0.015).3.5Survival analysis of16SNPs and the relationship with smoking historyThe genotype distribution in16SNPs were not statistically significant with smoking history (all p>0.05). Using Kaplan-Meier survival curves, and the log-rank test reveals that the genotype distribution in16SNPs were not statistically significant in prognosis (all p>0.05).4Conclusions4.1The onset age is highly correlated with the onset age and age of smoking initiation.4.2Preoperative smoking has no effect on the prognosis of esophageal cancer.4.3The genotype distribution in16SNPs were not statistically significant in prognosis. |
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