| Pancreatic cancer is known as a highly malignant gastrointestinal cancer with a similar mortality and incidence rate. The5-year overall survival rate of pancreatic cancer is less than5%. Recent years, the incidence and mortality of pancreatic cancer rises in worldwide. In fact, the secondary prevention programs and strategies are not well developped. As we all know, the key of effective secondary prevention in Chinese population is indentification of pancreatic cancer associated genetic factors and environmental risk factors. The susceptibility genes and gene mutations are involved as genetic factors. Environmental factors include smoking, drinking, high fat diet, exposure to carcinogens and the risk of some diseases such as diabetes, chronic pancreatitis. As reported, age and smoking are regarded as two important independent environmental risk factors in pancreatic cancer. The association between other factors and risk of pancreatic cancer is still in debate due to different research results. Here, we reported our study into two parts, aims to:1. To determine the pancreatic cancer prevalence risk factors, we studied the associtaion between risk factors such as environmental factors, disease factors and psychological factors and incidence of pancreatic cancer in Chinese population by stratified analysis and multivariate logistic regression study.2.To explore the relations of nuclear receptor gene NR5A2gene polymorphism (rs3790844, rs3790843and rs12029406) and genetic susceptibility in pancreatic cancer.3. To establish the theoretical model of pancreatic cancer risk factors in Chinese population and to find the secondary prevention strategy for pancreatic cancer.Part1:the study of pancreatic risk factorsMothods:We collected the questionnaires of patients with pancreatic cancer in Chinese Han population from four hospitals include Peking Union Medical College Hospital.The healthy subjects were matched to the cases. Clinical data were collected including demographics, smoking, drinking, diet, past history, family history, social stressevents and psychological status assessment. Univariate analysis and multivariate logistic regression methods were applied to assess the differences of various factors between pancreatic cancer group and control group. We also studied the correlation between environmental factors, disease factors and risk of pancreatic cancer.Results:1. The healthy control group was matched to pancreatic cancer group by sex, age (±5years old) in2:1ratio. A total of180questionnaires were completed in pancreatic cancer group, and360questionnaires in healthy control group.2.Univariate analysis showed the frequency of clinical factors with significant difference in the case and control groups as follows:smokers were41.67%and28.89%(P=0.0029) in pancreatic cancer group and healthy control group, respectively. The percentage of smoking more than22.5pack-years was21.11%and13.89%(P=0.0322). Alcohol consumption greater than76.8Cup-years was12.78%and6.67%, respectively (P=0.018). The incidence of diabetes was27.78%and8.89%, respectively (P<0.0001). The duration of diabetes were6.87±7.33years and12.53±11.33years, respectively. The percentage of past acute pancreatitis was5.56%and0.56%(P=0.0004). The percentage of past chronic pancreatitis was2.22%and0%(P=0.0013). Family history of pancreatic cancer was5.6%and1.7%in case and control group (P=0.012). The depression with severe depressed was14.44%and8.33%in two groups. The percent of severe melancholy frustrated was5.56%and0.83%(P=0.0003). The pecentage of mild to moderate remorse in control group was26.67%and11.67%, higher than16.11%and6.11%in case group (P=0.002). The percentage of mild and moderate anxiety in controls (47.78%) was higher than in cases (32.22%)(P=0.0188).3.By using binary logistic regression analysis, multivariate analysis between clinical factors and risk of pancreatic cancer showed:odds ratio (OR) of cigarette consumption>22.5pack-years was1.651(95%CI=1.228-2.219, P=0.0009) after adjustment of age, sex and drinking cup-years. OR of alcohol consumption>76.8Cup-years was0.966(95%CI=0.696-1.342, P=0.8373) after adjustment of age, gender and smoking. By adjusting age, sex, smoking and drinking, OR and P valu of other risk factors associated with pancreatic cancer were as follows:diabetes (OR=3.869,95%CI=2.331-6.422, P=0.000), disease duration<four years (OR=4.043,95%CI=1.231-13.282, P=0.021), history of acute pancreatitis (OR=12.606,95%CI,2.668-59.565, P=0.001), chronic pancreatitis history (P=0.999), the degree of depression (OR=1.353,95%CI=1.071-1.709,P=0.011), degree of remorse (OR=0.734,95%CI=0.561-0.960, P=0.024), and the degree of anxiety (OR=0.878,95%CI=0.686-1.125, P=0.303).Summary of Part1:Smoking, duration of diabetes less than four years, family history of pancreatic cancer and depression degree were associated with elevated pancreatic cancer risk in Chinese Han population. The history of acute pancreatitis may predict pancreatic cancer.Part2:Association of NR5A2gene polymorphism and risk of pancreatic cancer in Chinese Han populationMethods:The single nucleotide polymorphisms (rs3790844, rs3790843and rs12029406) of nuclear receptor superfamily NR5A2gene were genotyped by Taqman method in127patients with pancreatic cancer and127healthy controls. Then we studied the contribution of genotypes and haplotypes to risk of pancreatic cancer including smoking, alcohol consumption, diabetes, chronic cholecystitis, cholelithiasis and other possible risk factors by interact analysis and stratified analysis. Finally, the nonsuperiority test was used to determine the credibility of the negative results.Results:1.There was no significant association of NR5A2rs3790844, rs3790843and rs12029406polymorphism in pancreatic cancer (p>0.05).2. The nonsuperiority test showed Prs3790844=0.0980>0.05,Prs3790843=0.2950>0.05, Prs12029406=0.0107<0.05, which indicated rs12029406was not an independent risk factor of pancreatic cancer in northern China Han population and the association of rs3790844, rs3790843in pancreatic cancer was not determinated.3.Haplotype analysis in women showed rs3790844A-rs3790843C-rsl2029406T haplotype decreased pancreatic cancer risk (OR=0.16,95%CI=0.03-0.74, P=0.022) by comparing to rs3790844G-rs3790843T-rsl2029406T haplotype after adjusting for age, smoking and drinking. The result indicated that rs3790844A-rs3790843C-rsl2029406T haplotype might protect northern China Han women from pancreatic cancer.Summary of Part2:There was no significant association between NR5A2rs12029406and increased pancreatic cancer risk in northern China Han population. The correlation between rs3790844, rs3790843and pancreatic cancer needed to be further confirmed. Haplotype rs3790844A-rs3790843C-rsl2029406T might play a protective role in Chinese Han women from pancreatic cancer.Conclusion:Environmental factors (heavy smoking), disease factors (new-onset diabetes and family history of pancreatic cancer), and psychological and behavioral factors (depression, frustration) were significantly associated with risk of pancreatic cancer in Chinese Han population. The relationship between risk of pancreatic cancer and some single nucleotide polymorphisms (rs3790844, rs3790843)of NR5A2gene, which is a diabetes nuclear receptor and suspected as a highly risk factor in pancreatic cancer, have not been determinated and are needed to be further verified. There was no significant association between NR5A2rs12029406and increased pancreatic cancer risk in China Han population. |
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