Molecular Epidedmiology Of Esophageal Squamous Cell Carcinoma And Evaluation Of Early Diagnosis And Early Treatment In Yangzhong County, Jiangsu Province, China

Malignant tumor is a kind of disease that seriously affects human health and threatens human life span.Yangzhong County,Jiangsu Province is one of the places with high risk of cancer,the high incidence of esophageal cancer and stomache cancer has been heavy economic and life burden of local people.Researchs on potential risk factors of cancer,large scals of early diagnosis and early treatment is a must of local government and people.[Objective]This study is to investigate the role of polymorphisms of genes like: XPD,XRCC1,P53and MDM2,environmental factors and their interactions in the development of Esophageal Squamous Cell Carcinoma(ESCC);to investigate the role of P53and MDM2 protein expression and their relation with the clinical characters of ESCC;to evaluate the Early Diagnosis and Early Treatment(EDET) of ESCC Project and investigate people's knowledge and attitude towards ESCC.[Methods]A population-based case-control study was carried out in Yangzhong County,Jiangsu Province,China,with histologically confirmed ESCC cases who were diagnosis between Jan.2004 to Mar.2006 while controls were selected from the local cancer-free people and group matched with cases by sex and age.PCR-RFLP was used to detect the polymorphisms of XPD Lys751G1n,XRCC1 Arg399G1n,P53Arg/Pro和MDM2 SNP309 T/G and calculate the interaction with the environmental factors under multiple model.Histologically confirmed ESCC cases from Jan.2005 to Nov.2006 were also collected with paraffin-embedded slides and take another 10 cancer-free individuals with their paraffin-embedded slides. Immunohistochemistry of P53and MDM2 analysis was conducted with these samples.Colleting individuals take part in the EDET project from Sept.2006 to Aug. 2007;each was investigated with endoscope screening and knowledge and attitude towars ESCC.Epidata,SPSS 11.0 and Stata 9.2 statistical software was used to input and analysis data,x~2 tests and non-conditional Logistic Regression were used to study the assosiations with ESCC. [Results]Totally,355 cases(average age:61.5+7.9 years old) and 408 controls (average age:60.8+8.3 years old) were enrolled in the study.Stratified by sex and found cigarette smoking,alcohol drinking and family history have association with male ESCC.Compared with non-smokers,former smokers have a of 2.80(95%CI. 1.38-5.67),current smokers have a risk of 1.41(95%CI:0.91-2.18alcohol drinkers have a risk of 1.84(95%CI:1.23-2.77);people whose both parents having ESCC have a risk of 3.39(95%CI:1.25-9.19).Education and family history have association with female ESCC.Middle School and above have a risk of 3.56(95%CI: 1.17-10.58)and people whose either parents having ESCC have a risk of 2.26(95% CI:1.31-3.90).Compared with wild type Lys/Lys,male case with XPD Lys/Gln+Gln/Gln genotype have a risk of 1.64(95%CI:1.01-2.65) of developing ESCC,adjusted by age, cigarette smoking,alcohol drinking and family history and get an OR of 1.58(95%CI: 1.00-2.49).Compared with wild type Arg/Arg,female cases with Arg/Gln+Gln/Gln genotype have a risk of 1.46(95%CI:0.89-2.41) of developing ESCC,adjusted by age,cigarette smoking,alcohol drinking and family history and get an OR of 1.64(95%CI:1.01-2.66).Crossover tests shows a significant interaction between cigarette smoking,alcohol drinking and ESCC in male cases with OR of 2.01(95%CI:1.14-2.76) and 4.47(95%CI:1.71-11.64).Compared with wild type Arg/Arg,individuals with P53Pro/Pro have a risk of 4.09(95%CI:2.34-7.12) of developing ESCC,adjusted by sex,age,cigarette smoking,alcohol drinking and family history and get an OR of 4.05(95%CI: 2.30-7.16).Compared with wild type T/T,individuals with T/G and G/G have a risk of 1.88(95%CI:1.39-2.55) and 6.13(95%CI:3.99-19.450 of developing ESCC, adjusted OR are 1.52(95%CI:1.12-2.06) and 8.82(95%CI:3.99-19.45).Cigarette smoking have an interaction with P53Arg/Pro,OR is 1.54(95%CI:1.02-2.33), alcohol drinking have interactions with MDM2 309 T/T,OR are 1.73(95%CI: 1.04-2.88).Compared with wild type of P53and MDM2,when MDM2 has mutation, OR is 4.72(2.45-9.56);when P53has mutation,OR is 5.07(95%CI:2.85-9.36);when both P53and MDM2 have mutation,OR is 12.60(1.67-560).Immunohistochemistry analysis detected a P53positive rate of 70.77%while MDM2 positive rate is 74.8%.There was no association with P53and MDM2 protein expression.MDM2 expression was associated with tumor stage,stageⅡpatients have a high level of expression.There were no association between P53gene mutation and P53protein expression,neither do MDM2 gene mutation and MDM2 protein expression.1797 people were recruited from Sept.2006 to Aug.2007 in the EDET project.The average age of the investigator was 52.65±8.55 years old.43 new patients were detected and among the 32 ESCC 25 were in the early stage.For willingness to pay out-of-pocket for physical examination,the median fee was l00 rmb.The median score of cancer knowledge is 44,25%quantile is 31 and 75%quantile is 56.Orderial Logistic Regression shows the scores have relation with family history,alimentary canal history,sex,income and education.[Conclusion]XPDLys751Gln polymorphisms were associated with male individual susceptibility to ESCC in Yangzhong County and XRCC1 Arg399Gln polymorphisms were associated with female individual susceptibility to ESCC. P53codon 72 Arg/Pro and MDM2 polymorphisms were associated with individual susceptibility to ESCC.The expression of MDM2 protein was associated with tumor stage,stageⅡpatients have a high level of expression.EDET detected 43 new cases; risks for cancer knowledge scores were family history,alimentary canal history,sex, income and education.