| 1. Background and PurposeThe prognosis of patients with advanced esophageal cancer (EC) remains very poor, with a5-year survival rate of only about10%. Over the past decade years for field study in high incidence areas for EC, we have found that there are few patients who could survive over10years with the disease-free, not alone20or more years. Obviously, it is difficult to explain this phenomenon just from the clinical features and morphological changes, so we speculate that there may be some molecular mechanisms involved in the prognosis of EC. Our recent genome wide association study (GWAS) have showed that the single nucleotide polymorphism (SNP) at rs4908343within AT hook DNA binding containing1gene (AHDC1) is highly correlated with the susceptibility to EC. The AHDC1gene, located on chromosome1p36.13, has been reported with ataxia pathogenesis. The protein coded by AHDC1can affect chromosome structure and transcriptional regulation of AT-rich region, and participate in the repair of DNA damage. We assume that the variation of AHDC1gene may be related to the prognosis of patients with EC, and analyze comprehensively the relationship between the two studies with clinical pathological features in order to deepen the understanding of the molecular mechanisms of EC prognosis. This study might provide the clues for the establishment of an objective evaluation system for EC prognosis, then we can handle the risk of prognosis early to improve the living conditions of the patients and to increase survival time. 2Materials and Methods2.1Patient populationIn this study,3,478patients mainly (82%) came from the junction of Henan, Hebei and Shanxi provinces called the high incidences areas of EC of Taihang Mountains. All the patient information was from the database of Henan Key Laboratory for Esophageal Cancer in Zhengzhou University. Of the3,478EC patients, there were2,111males with a mean age of59±9and1,367females with a mean age of60±9. The ratio of male to female was1.5:1. Based on the different treatments (radiotherapy, chemotherapy and other conservative treatment), the patients were divided into two groups, i.e., the surgical and non-surgical group.2.2Follow-up and blood samples collectionHome visits manner, questionnaire and telephone manner were applied to follow-up the survival information of3,478patients with EC, with deadline is December18,2011. The follow-up focused on patients who were alive or death and the cause of death, etc. We verified the pathological information of patients though the departments of pathology in hospitals.5ml fasting peripheral blood samples (EDTA anticoagulant) was collected from each patient, the informed consent was obtained for each participate.2.3AHDC1genotypingTaqman(?) genotyping technology was used to detect the genotype of rs4908343locating at AHDC1gene. The upstream and downstream primers of rs4908343were5’-AACCAGGGTCTGACTAACTCC-3’and5’-GTTGAAGTGCCAAGAAAGGA-3’. The two Taqman probes were5’-FAM-TGGGCTATGACAAAGAG-MGB-3’and5’-HEX-TGGGCTATGACAAGGAG-of MGB-3’.2.4Statistical analysisUsing SPSS17.0statistical software, the influence of sex, treatments, the high-and low-incidence areas, lymph node metastasis, clinical stages and AHDC1genotypes count on the prognosis of patients was analyzed by Kaplan-Meier and Log-rank test; and multivariate analysis was performed using Cox proportional hazards regression model; Hardy-Weinberg equilibrium was used to test the crowd coincide degrees of rs4908343loci; chi-square test the relationship of the distribution of AHDC1genotype and lymph node metastasis, and clinical stages (a=0.05was considered as the test standard).3. Results 3.1There were2,416patients followed-up successfully during3,478patients, with the success rate was69.5%. The patients with EC who came from the high incidence areas (Henan, Hebei, Shanxi, etc) constituted95%(2046cases) of the population that successfully surveyed; in contrast,370(5%) patients were from the low incidence areas (Shandong, Jiangsu, Hubei, etc) for EC. According the follow-up, there were1,574cases alive (65%) and842deaths (35%). All the dead patients were because of EC.3.2Consistent with Hardy-Weinberg equilibrium, observed and expected value had people representative through the crowd goodness of fit tests (χ2=0.031, P>0.05).3.3There was no significant correlation between the variation of AHDC1genotype with depth of tumor invasion, lymph node metastasis, clinical stages, degrees of differentiation, treatments, and the high-and low-incidence areas of EC (P>0.05).3.4The5-year survival rate of patients of EC with AA/AG genotypes of AHDC1was46%, in contrast, the GG type’s5-year survival rate was38%. There was a statistically significant difference between AA/AG and GG genotypes (χ2=6.650, P <0.05).3.5The different5-year survival rates were observed in the patients with invasion to fiber, muscle and mucosa layers (21%,37%,54%, respectively; χ2=52.756, P<0.05).3.6The different5-year survival rates were observed in the patients with lymph node to positive and negative metastasis (15%,38%, respectively; χ2=39.087, P<0.05).3.7The different5-year survival rates were observed in the patients with clinical stage to the early, the middle and the advanced stages (55%,31%,15%, respectively; χ2=61.314,P<0.05).3.8The different5-year survival rates were observed in the patients with differentiation to the well, the moderately and the poorly differentiations (39%,24%,23%, respectively; χ2=3.015, P>0.05).3.9The same5-year survival rates were observed in the patients with the sex to male and female (43%,48%, respectively; χ2=2.734, P>0.05).3.10The different5-year survival rates were observed in the patients with the treatment to undergoing surgery and non-surgical treatments (49%,22%, respectively; χ2=75.635, P<0.05).3.11The different5-year survival rates were observed in the patients with the area to the high incidence, low incidence areas of EC (51%,9%, respectively;χ2=175.205, P <0.05). 3.12Cox multivariate regression analysis was used to analyze the relationship of AHDC1genotypes, clinical stages, the high and low incidence areas and treatments with the survival time. The results showed that AHDC1genetic variation had a significant effect on the prognosis of patients with EC (P<0.05), the risk of the GG type of death in patients was higher than the AA/AG type (HR=1.197,95%CI=1.008,1.421); clinical stages were the risk factor to the survival of patients of EC (P<0.05), the risk of death of the patients who were in middle period was2times of the early patients (HR=2.004,95%CI=1.358-2.956), and the advanced patients’ were almost4times of the early (HR=3.594,95%CI=2.392-5.399); the patients in the high incidence areas had longer survival time than that of low incidence areas (P<0.05), Cox regression showed that the patients in high incidence areas had lower risk of death than patients in low incidence areas (HR=2.891,95%CI=2.242-3.726); the difference of the treatment was not statistically significant (P>0.05). So the high-and low-incidence area, clinical stages and AHDC1genotypes were independent prognostic factors of EC.4Conclusions4.1The variation at rs4908343loci is significantly related with the prognosis of patients of EC, and the AA/AG type is the protective factor for the prognosis of EC.4.2The variation at rs4908343loci does not significantly relate with the depth of invasion, lymph node metastasis, clinical stages, the degree of differentiation, treatments and the high-and low-incidence areas.4.3The depth of invasion, lymph node metastasis, clinical stages, the high-and low-incidence areas have a significant correlation with the prognosis of patients of EC.4.4The sex, treatments and differentiation of tumor do not significantly relate with the prognosis of patients of EC. |
PDF Full Text Request