The Relationship Between Gross Type Of Advanced Esophageal Cancer And Rs7946005Locus Variation And Its Impact On Prognosis

1Background and purposeEsophageal cancer is one of the most common malignant tumor in China. Clinically, patients with esophageal cancer in the first visit, more than90%is already advanced. Advanced esophageal cancer has a relatively clear general form. In the late1950s, based on the growth of tumors in different ways, the gross type of esophageal cancer was summarized in four main types, ulcer, medullary, fungating and narrowing type. These classifications contribute to guide for the clinical treatment and prognosis of esophageal cancer, and has been in use today. However, the molecular basis of the growth of the general type of advanced esophageal cancer is unclear. As the change of time and environmental factors, if the proportion of patients with gross type changing corresponding, and the relationship between the clinical pathological TNM staging, as well as its effect on esophageal cancer survival is still lack of large samples and comparison of different time periods. Genetic factors on general growth of esophageal cancer are less clear. This study aims to through the system analysis27,966cases of esophageal cancer from1983to2012by pathological diagnosis of esophageal squamous cell carcinoma in general growth characteristics of the type of clinical pathology and its relationship with TNM stage. Further we combine the type of esophageal cancer with the main variable sites SNP (rs7946005) in genome-wide association analysis of esophageal cancer, to clarify these factors influence on the survival of advanced esophageal cancer, and provide the basis for molecular classification. 2Materials and Methods2.1Patients27,966cases diagnosed as esophageal squamous cell carcinoma in1983to2012, which from Henan Province esophageal biological samples database.17,919patients of male median age are59.00years, age range26-96y;10,047patients of women median age are59.90years, age range21-90years, male to female ratio is1.7:1.2.2Households survey, Verification hospital data and Follow-upHousehold survey or phone follow-up to record the 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 September14,2013.2.3Blood samples, DNA extraction and Taqman genotypingPatient consent, signed informed consent, each patient collecting5ml EDTA anticoagulated peripheral venous blood. Using Flexi Gene DNA extraction kit (Qiagen) to extract the cell genomic-wide DNA in the blood samples. Using Taqman (?) genotyping technology detects TENM4gene rs7946005locus.2.4Statistical analysisAll data were statistically analyzed using SPSS17.0. Count data using x2test; The survival rate was calculated Kaplan-Meier method and Log-rank test to analyze the differences between the different survival group; influencing factors using Cox proportional hazards regression model to analyze the prognosis of patients with esophageal cancer. Test level:a<0.05.3Results3.1The distribution of four general types of advanced esophageal cancer Four general types of advanced esophageal cancer, the most common was ulcer type, accounting for45.2%, followed by medullary and mushroom umbrella, accounting for39.3%and11.0%respectively, at least narrowing type, accounting for4.5%.3.2changes of the distribution of four general types of advanced esophageal cancer in the three decadesFour kinds of gross type in three decades, ulcer type was the most common, medullary and fungating second, narrowing type least. And narrowing type had gradually increased in three decades (P<0.05).3.3The clinical and pathological features of four general types of advanced esophageal and factors impacting on survivalFour general types differed in the distribution of men and women (P<0.05). The proportion of ulcer type with man was more than women, and women’s medullary and fungating types more than men (P<0.05).The distribution of four general types in two different ages, followed as≤50years old and>50years, was different ((P<0.05) The distribution of four general types in high and low incidence areas, urban and rural, and family history of positive-negative that was different, and the difference was statistically significant (P<0.05).The distribution of four general types in tumor location, the degree of invasion, lymph node metastasis, and degree of differentiation was different, and the differences were statistically significant (P<0.05). The proportion of ulcer type in lower section was higher than on the up and middle (P<0.05), while medullary and narrowing type in the up and middle section were higher than the lower section (P<0.05); The proportion of ulcer type with well and middle differentiation is higher than poor differentiation, while narrowing type was the opposite.(P<0.05); narrowed type was more easier metastasis in lymph node than fungating type(P<0.05); the ratio of narrowed type in T3, T4is higher than T1-T2(P<0.05). Single factor survival analysis was carried out on the different clinical and phathological information, and found that gender, age, T staging, lymph node metastasis and esophageal pathology classification were related to the prognosis of patients with esophageal cancer. After multi-factor survival analysis found that gender, age, T staging, lymph node metastasis status were independent prognostic factors of esophageal cancer patients.3.4The relationship between rs7946005loci gene polymorphisms and clinicopathologic features on esophageal cancer and its impact on survivalHardy-Weinberg equilibrium test showed that rs7946005locus in genotype was balance in the distribution of genetic population (P=0.15). Different genotype of rs7946005and clinicopathological features, such as gender, age, gross type,had no correlation(P>0.05). However, rs7946005locus different genotypes of survival, and the difference was statistically significant (P<0.05). Survival of the mutant TT genotype is superior to the other two types (CT and CC).4Conclusion4.1The general types of advanced esophageal have close relationship with clinicopathological features, but survival has no obvious difference between four general types;4.2rs7946005genotype is not associated with general types;4.3rs7946005genotype is relate to esophageal cancer survival, mutation TT type has better prognosis.