The Association Between The Single Nucleotide Polymorphisms Of Diabetes-associated Gene And Pancreatic Cancer:a Case-control Study

BACKGROUNDPancreatic cancer is the most malignant digestive system tumors with poor prognosis. The incidence of pancreatic cancer increased rapidly. Because of the atypical clinical manifestations, and rapidly metastasis, lacking of effective early diagnosed methods, about half of the patients lost the surgery opportunity when they were diagnosed. Also, pancreatic cancer is not sensitive to the current chemotherapy and radiotherapy,5 years of survival rate is less than 5%. Moreover, more than half of the patients died within half a year when they are diagnosed. So, the situation is very serious. Early diagnosis is the key to improve the prognosis of pancreatic cancer.A single nucleotide polymorphism (SNP) is a variation in a single nucleotide which could occurs at any position of the genome, widely distributed in the human genome. Functional SNPs were thought to be the reasons of some diseases,could induce some tumors developed. So far, SNPs are now thought to be a prospect biomarker in the field of tumor diagnostic, prognostic, and predictive.Diabetes is closely associated with pancreatic cancer, is considered to be a risk factor for pancreatic cancer or its associated symptoms. A meta-analysis reported that the risk for pancreatic cancer is 82% higher among diabetics compared with those without diabetes. However, the underlying factor still remain to unknown. A lot of SNPs has be found associated with diabetes, So, we guess may these SNPs are the bridge combined diabetes and pancreatic cancer.OBJECTIVETo discussion the correlation between single nucleotide polymorphism (SNP) associated with diabetes and pancreatic cancer, and to search for a suitable biological indicator as an early screening for those of high-risk of pancreatic cancer.METHODSWe genotyped five SNPs selected upon literature reviewed, which were closely related to diabetes, reported in the field of colon cancer, breast cancer et al, but were rarely studied in pancreatic cancer, including TCF7L2 (rs290487), TCF7L2 (rs7903146), GCKR (rs780094), PPARG (rsl801282), ADIPOQ (rsl501299).We examined their associations with pancreatic cancer risk in a case-control study including 198 cases and 200 controls from the Second Affiliated Hospital of Zhejiang University of Medicine. Collected detailed information on their lifestyle factors (include gender, age, BMI, smoking history, drinking history, history of diabetes, and family history). DNA was extracted from 2ml peripheral blood. Genotyping was performed using Snapshot SNPtype assays.Genotypes in case and control groups were evaluated Chi-square test. Logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between these diabetes related SNPs and pancreatic cancer risk.RESULT1、Cigarette smoking, drinking, history of diabetes is a risk factor for pancreatic cancer, after multiariable analysis, found that drinking was not associated with pancreatic cancer, and smoking has been related risk factors of pancreatic cancer and diabetes (cigarette smoking:OR=2.288,95%CI:1.249-4.193, P=0.007; history of diabetes:OR=12.090,95%CI:6.038-24.209, P< 0.001; drinking history:OR=1.510,95%CI:0.811-2.812, P=0.194=.2、With the exception of rs290487 in the TCF7L2 gene (P=0.010), no significant differences in other 4 SNP were found between cases and controls. SNP rs290487 in the TCF7L2 gene was positively associated with pancreatic cancer risk, for T/T genotype vs C/C genotype, OR was 2.093,95%CI:1.183-3.703. However, C/T genotype didn’t show differences between cases and controls. After adjustment for age, sex, cigarette smoking, drinking and diabetes history, the C> T varies in rs290487 was still the risk factor for pancreatic cancer (C/T-17T genotype vs C/C genotype:OR=1.916,95%CI:1.064-3.449, P=0.030).3、In the hierarchical analysis, we observed T-SNP was the pancreatic cancer risk factor in cigarette quitting group (T/T genotype:OR=2.440,95%CI: 1.201-4.955, P=0.012), but did not found significance in cigarette smoking group. Drinking degree was not found statistical significance with the risk of pancreatic cancer (P> 0.05), In non-drinking patients, rs290487 C> T polymorphism is a risk factor for pancreatic cancer (T/T genotype, OR= 2.156, 95% CI:1.0854.283, P= 0.027).4、With the exception of rs7903146 in the TCF7L2 gene, other 4 SNPs were all associated with the diabetes mellitus (DM)CONCLUSION1、 Rs290487 TCF7L2 gene single nucleotide polymorphisms (C> T) associated with pancreatic cancer, is a independent risk factor for pancreatic cancer occurs.2、Cigarette smoking is a risk factor for pancreatic cancer occurs, and pancreatic cancer risk associated with the degree of smoking. In the case of not smoking, TCF7L2 gene single nucleotide polymorphism (C> T) is associated with the occurrence of pancreatic cancer.