Trends In Mortality Of Upper Gastrointestinal Cancer In The Risk-region Of Esophageal Cancer And Study On Molecular Mechanisms

Incidence rates have risen for gastric cardia adeno- carcinoma and have decreased for noncardia adenocarcinoma, while rates have remained stable for esophageal squmous cell carcinoma in many western countries. Cixian County and Shexian County both are the high-risk areas for esophageal cancer in China, as well as in the world. Cixian County and Shexian County are also geographical regions which have very high incidences of esophageal cancer, cardia cancer and noncardia cancer. Detailed epidemiological analyses of their demographic trends and risk factors will help guide future cancer control strategies. The aim of this study was to describe and analyze trends in mortalitye rates for esophageal cancer, gastric cardia cancer and noncardia cancer for 29 years.In our study, considerable evidence exists that reduced DNA repair capacity may increase the risk of tumor.Nucleotide Excision Repair (NER) is a versatile in DNA repair systems. XPA play an important role in NER.Because a deficiency in XPA is associated with an increased risk of tumor. We investigated the association of polymorphisms of XPA with the risk of susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. According to the results, we can put out a project with pertinence and serve for solving down-to-earth matter.Part 1 Trends in Mortality of the Upper Gastrointestinal Cancer in the High-risk Regions of Esophageal CancerObjective : We studied the mortality rates of upper gastrointestinal cancer in CiXian, SheXian which are the high-risk regions of esophageal cancer of Hebei province China from 1974 to 2002. We found out the difference of trends and characteristics between the two regions in order to provide clue for upper gastrointestinal cancer. We can put out a project with feasibility.Methods:Hebei Cancer Institute has carried out three investigations on the cause of death of malignant tumor, in 1970′s(from 1974 to 1976),1980′s(from 1984 to 1986),1990′s(from 1990 to 1992) respectively in SheXian and CiXian. Data of the new century (from 2000 to 2002) come from the registery department of SheXian and CiXian.The register was conducted by the three-level prevention web in CiXian and SheXian. Each clinic doctor in every township (prevention web I) was required to report each new case of cancer occurring in the township by a standard card, then the cards were send to the clinic of the rural administration unit (prevention web II).They were sorted and sent to the Cixian Cancer Registry and Shexian Cancer Registry (prevention web III) once a month. They checked the quality of the registration.We calculated the standard rate of mortality of China using the population of 1982, and the standard rate of mortality of world using world population of 1985 using the direct method.All the data was checked and analyzed by SPSS11.5 software. For evaluation of incidence trends,we have used alinear regression analysis based on the logarithm of observed incidence rates.Logarithmic transformation was preferred specifically because this facilitates the comparison of trends at varing incidence levels.A model fitting this data is the logarithm Y=ABX whimatich represents a linear regression model,where Y is the estimated incidence rate per100,000 of the population and X is the calendar year minus the initial year for the current data.If therefore the estimated rate of the initial year and(B-1)*100 gives the average annual percentage change in the incidence rate,during this period.The carcinoma was coded according to International Classification of DiseaseⅨ(ICD-9) and X (ICD-10).Results: Mortality tends: From 1970 ' s to the new century,the mortality rate of esophageal cancer has a trend of descending in CiXian and SheXian,the mortality rate are 127.14/105, 103.17/105 , 86.18/105 and 126.37/105, 78.73/105, 59.49/105. The mortality rate of esophageal cancer is descend of 40.96/10,000 in CiXian and of 65.74/10,000 in SheXian The mortality rate of cardia cancer are 8.72/105,6.14/105,9.11/105 in CiXian and 13.60/105,22.91/105,44.18/105 in SheXian. The mortality rate of cardia cancer has not more alteration in CiXian. The mortality rate of cardia cancer has been increased obviously in SheXian.The mortality rate of noncardia gastric cancer are 17.33/105,24.16/105,16.59/105 and 71.14/105,62.82/105,36.70/105 , respectively in CiXian and SheXian.The mortality rate of noncardia cancer is not more alteration in CiXian and it is descending obviously in SheXian.Sex ratio: The sex ratio (male vs female) are 2.12,2.38,2.45 and 1.75,2.09,2.11 respectively in CiXian and SheXian. Mortality rate of age group: The mortality rate of upper gastrointestinal cancer increased in accordance with age. The geographic trends: The highest mortality rate area is mountain region in CiXian. The annual average mortality of cardia cancer is 11.21/105.Conclusion: Mortality rate of esophageal cancer has presented a descending trend in the past 29 years in CiXian and SheXian.The mortality of cardia and noncardia cancer have changed fluctuantly in rescent decades in CiXian. The cardia cancer has been increasing, while the noncardia cancer has been decreasing in SheXian. Part2 Correlation of Nucleotide Excision Repair Gene XPA Polymorphisms to Esophageal Squamous Cell Carcinoma and Gastric Cardiac AdenocarcinomaObjective: The polymorphisms of XPA (A23G, at posit- ion-4 from the ATG start condon) was genotyped by polymerase chain reaction–restriction fragment length poly-morphism (PCR-RFLP) analysis in 327 ESCC patients, 253 GCA patients and 612 controls.Because of the importance of maintaining genomic integrity in the general and specialized functions of cells as well as in the prevention of carcinogenesis, genes coding for DNA repair molecules have been proposed as candidate cancer- susceptibility genes. Xeroderma pigmentosum (XP)-A was involved in nucleotide excision repair (NER), Single nucleotide polymorphisms (SNP) in XPA gene may modify DNA repair capacity and genetic susceptibility to cancer. Polymorphisms in the exon may lead to amino acid change, which may cause the function alteration of the coding protein in some extent. Polymorphisms in the intron may affect DNA Repair Capacity (DRC) by linking to other cancer- susceptibility genes or leading to abnormal splice, which at last results in the difference of susceptibility to cancer.We investigated the association of two polymorphisms of XPA with the risk of susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of high incidence region of Hebei Province.Methods: This population-based case-control study included 580 cancer patients (327 with ESCC and 253 with GCA) and 612 controls. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. Polymorphisms of XPA gene was analyzed by PCR-restriction fragment length polymorphism analysis (RFLP) and primer- introduced restriction analysis PCR (PIRA-PCR).Statistical analysis was performed using SPSS11.5 software package.P<0.05 was considered significant for all statistical analyses.Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in study groups using Chi-square test. Comparison of the XPA genotype, allelotype and haplotype distribution in cancer patients and controls was performed by means of two-sided contingency tables using Chi-square test. The odds ratio (OR) and 95% confidence Interval (CI) were calculated using an unconditional logistic regression model and adjusted by age, gender, smoking status and family history of upper gastrointestinal cancer(UGIC) accordingly.Results1 The frequency of positive family history of upper gastrointe- stinal cancer (UGIC) in ESCC (48.0%) and GCA (47.8%) patients was significantly higher than that in controls (34.2%) (χ2=17.22 and 14.19, P=0.000). Family history of UGIC may increase the risk of developing ESCC and GCA (age, gender and smoking status adjusted OR=1.80 and 1.75, 95% CI = 1.36-2.38 and 1.29-2.36, respectively).2 The overall genotype and allelotype distributions of XPA A23G in ESCC patients were significantly different from that in controls(P<0.05). The A/G+G/G genotype significantly decreased the risk of developing ESCC compared with A/A genotype. (Adjusted odds ratio (OR) =0.60; 95% confidence interval (CI) =0.45~0.80).3 When stratified for smoking status, the A/G+G/G genotype was associated with a significantly decreased risk for ESCC in non-smokers (adjusted OR=0.64; 95% CI=0.44~0.93) and smokers (adjusted OR=0.54; 95%CI=0.35~0.84).4 When stratified for family history of UGIC, compared with A/A genotype, A/G+G/G genotype significantly decreased the risk of ESCC in groups with negative history of UGIC. (Adjusted OR=0.54; 95%CI=0.37~0.78).5 The overall genotype and allelotype distributions of XPA A23G in GCA patients were not significantly different from that in controls(P>0.05). Compared with A/A genotype, A/G+G/G genotype significantly decreased the risk of GCA. (Adjusted OR=0.70; 95% CI=0.51~0.86).6 When stratified for smoking status, the genotype distributions of XPA A23G in GCA patients were significantly different from that in control(sP<0.05). Compared with A/A genotype, A/G+G/G genotype significantly decreased the risk of GCA in non-smoker group. (Adjusted OR=0.55; 95% CI= 0.36 ~0.85).Conclusions1 Family history of UGIC increases the risk of developing ESCC and GCA.2 The A/G+G/G genotype significantly decreased the risk of developing ESCC compared with A/A genotype.3 The A/G+G/G genotype was associated with a significantly decreased risk for ESCC in non-smokers and smokers.4 Compared with A/A genotype, A/G+G/G genotype signif icantly decreased the risk of ESCC in groups with negative history of UGIC.5 Compared with A/A genotype, A/G+G/G genotype signi- ficantly decreased the risk of GCA.6 Compared with A/A genotype, A/G+G/G genotype signi- ficantly decreased the risk of GCA in non-smoker group.