| BackgroundsAs medical technology advances, the treatment and prognosis of some forms of cancer have been greatly improved while those of pancreatic cancer (PC) is still in a relatively different situation. According to the latest statistics, PC is the eighth leading cause of cancer-related death in the world and fourth in the developed countries with approximately266000deaths each year. Being one of the most lethal malignant carcinoma in digestive system, PC is characterized by a very poor prognosis due to the asymptomatic nature in early stage and rapid progression thereafter, with most patients dying within12months after diagnosis. Although for the pancreatic cancer patients in early phases, the5-year survival rate after surgery has exceeded to approximately20%, the5-year overall survival rate is only about5%. Therefore the recognition of risk factors and application of primary prevention for pancreatic cancer is of vital importance in the treatment and prognosis of the disease.Risk factors associated with PC can be divided into two main categories. One is the genetic factors. At present, because of the rapid developments in genomics and epidemiology, many studies have proved that some kinds of gene polymorphisms are associated with PC. It has been proved that vitamin D (VD) as a kind of hormone, can significantly inhibit the proliferative activity of many cancer cells included pancreatic cancer cell in vitro and the dietary VD or sunlight exposure may be protective from PC. However, little is known about association about vitamin D receptor (VDR) gene polymorphisms with PC.The other is environmental factors and modifying factors, such as smoking, alcohol, obesity and chronic pancreatitis (CP). In the last5years, some cohort and case-control studies have been conducted to estimate the relationship of hepatitis B virus (HBV) status and PC. The results were controversial.This study is divided into two parts, respectively. In part one, we investigate the relationship of VDR gene rs2228570、rs1544410polymorphisms and PC; in part two, a case control study and an updated meta analysis are performed to discuss the relationship of HBV status and PC.Part1The association of vitamin D receptor gene rs2228570、rs1544410polymorphisms with pancreatic cancerAs one kind of nuclear receptor protein, VDR is widely distributed in different body cells. The first and classical function of VDR is to adjust the calcium-phosphorus balance in blood. As the recently studies, VD and VDR also can regulates cell cycle, inhibit cell proliferation and promote cell differentiation and apoptosis. So many researches have focused on the association of the expression of VDR and VDR gene polymorphisms with different tumors. We conduct the case control study to investigate the relationship between VDR gene polymorphisms and the onset risk, location, TNM classification and pathological differentiation of PC separately. Objective and methodsIn this part, we perform a case control study to value the relationship of VDR gene rs2228570、rs1544410polymorphisms and PC respectively. In this study,258PC patients and385healthy controls were enrolled. The genotypes of rs2228570and rs1544410were assayed using the method of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analysis was done to determine the association of onset risk with gene polymorphisms. Contingency table analysis was done to value the relationship between gene polymorphisms and the location, the TNM classification and pathological differentiation of PC.Result1. rs2228570polymorphisms and PCIn the univariate regression analysis and multivariate logistic regression analysis adjusted by age, gender, history of tobacco, history of alcohol and diabetes, the genotype TT can increase the risk of PC significantly (univariate: OR=3.024,95%CI=1.919-4.764, P=0.005; multivariate:AOR=2.978,95%CI=1.844-4.81, P=0.0006); the genotype with at least one T gene loci can increase the risk of PC significantly (univariate:OR=2.424,95%CI-1.718-3.420, P=0.001; multivariate:AOR=1.995,95%CI=1.311-3.035, P=0.0013); the frequencies of T allele in PC group was significantly higher than in controls (OR=1.869,95%CI=1.489-2.347, P=0.0001). In the contingency table analysis, the rs2228570polymorphisms were correlated with pathological differentiation of PC significantly.2. rs1544410polymorphisms and PCIn the univariate regression analysis and multivariate logistic regression analysis adjusted by age, gender, history of tobacco, history of alcohol and diabetes, the genotype with at least one G gene loci could decrease the risk of PC significantly (univariate:OR=0.631,95%CI=0.449-0.887, P=0.008; multivariate: AOR=0.648,95%CI=0.453-0.928, P=0.0179); the frequencies of G allele can decrease the risk of PC significantly (OR=0.756,95%CI=0.603-0.947, P=0.015). In the contingency table analysis, the rs1544410polymorphisms were correlated with TNM classification of PC significantly.Conclusion1.In this study, the VDR gene polymorphisms were significantly correlated to with the onset risk of PC. In rs2228570, the T loci and genotype with T allele could increase the risk of PC; in rs1544410, the G loci and genotypes AG+GG could decrease the onset risk of PC significantly.2.The VDR gene polymorphisms were correlated with pathological differentiation and TNM classification of PC significantly. So these polymorphisms might affect the prognosis of this disease.Part2The association of hepatitis B virus status with pancreatic cancer including a case control study and an updated meta analysis.HBV is still responsible for heavy disease burdens in China. Chronic HBV status refers to the infection of HBV for more than6months, this infection status could attribute to a history of acute HBV infection or infant period HBV infection in which the hepatitis B virus are not completely cleaned up due to the imperfect development of the immune system. In2006, according to the Ministry of Health of China, the national prevalence of HBV was about7%. And today, more and more researches were focused on the occult HBV status which is significantly associated with simply presence of anti-HBc antibody. Several studies found that HBV could replicate in human pancreatic tissue and that patients with HBV infection have impairments of pancreatic function. Some cohort and case-control studies have been conducted to estimate the relationship between HBV status and PC, providing somewhat conflicting results. In this part, we conducted a case control study and update the meta analysis to investigate the relationship of HBVstatus and PC. Objective and methodsIn this part, we perform a case control study and a meta analysis to further value the relationship of HBV status and PC. In the case control study,258PC patients and385healthy controls were enrolled. Nine studies were included to perform the meta analysis together with the result of our case control study. The characteristics of the patients and controls were collected such as age, gender, history of tobacco and alcohol exposure and diabetes. Univariate and multivariate logistic regression analysis was done to determine the association of PC onset risk and HBV; contingency table analysis was done to value the relationship between HBV and the location, the TNM classification and the pathological differentiation of PC. The adjusted RRs, HRs or ORs were collected to compute a summary OR and95%CI. HRs, RRs were directly considered as ORs. Heterogeneity across studies was tested using the Q and I2statistic. Stratified meta analysis was conduct according to region and study design.ResultIn the univariate regression analysis and multivariate logistic regression analysis adjusted by age, gender, history of tobacco, history of alcohol and diabetes, the chronic HBV infection can increase the risk of PC significantly (univariate:OR=2.380,95%CI=1.556-3.606, P=0.001; multivariate: AOR=3.339,95%CI=2.081-5.358, P=0.001), in the the stratified analysis according to HBV serological markers, the group HBsAg+/anti-HBcAb+can increase the risk of PC significantly; the occult HBV carrier status also can increase the risk of PC significantly, the AOR was1.163(95%CI=0.774-1.747, P^O.031). In the meta analysis, the overall OR was1.392(95%CI=4.167-1.660, P=0.00) assembly to the result of submeta analysis according to region. Only a borderline significant association was observed when combining all cohort studies (OR-1.307,95%CI=0.966-1.715, P=0.053). Given cohort study was more powerful to detect a causal relationship than case-control one, this result should be interpreted with caution. In the contingency table analysis, the HBV status was correlated with pathological differentiation of PC significantly. Conclusion1.The chronic HBV infection and occult HBV carrier might increase the onset risk of PC significantly, but further multi-center large sample clinical studies especially cohort studies are required to investigate the relationship.2. The HBV status was correlated with pathological differentiation of PC significantly. So hepatitis B virus might affect the prognosis of the disease. |
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