Etiology Of Pancreatic Cancer Research Articles

Abstract 5376: Expression of histone deacetylases (HDACs) 1, 2, 3 and 7 in pancreatic cancer cell lines: The role of indole-3-carbinol.

Abstract Pancreatic cancer has the poorest prognosis of most cancers, mainly due to its resistant phenotype. Early or late biomarkers are greatly needed in this cancer. Scientists have shown that epigenetic mechanisms may be involved in the etiology and progression of pancreatic cancer. Epigenetic changes involve modification of the DNA through hyper- and hypo-methylation, histone modification and modulation in expression of microRNAs. Histone deacetylases modify tails on the histones, which can result in repressive chromatin formation and inactivation of specific genes. This study, using real-time PCR, examined the level of HDACs 1, 2, 3 and 7 in four pancreatic cancer cell lines (BXPC, CFPAC,ASPC and MIA). The highest level of expression of HDAC 1 and 3 was found in CFPAC and MIA cells compared to BXPC and ASPC cells. Indole-3 carbinol, in previously published studies from our laboratory, have shown several anti-cancer activities, including the re-expression of p16 in MIA cells (Lyn-Cook et al, 2010 Anticancer Res., 30:4907-4914). The current study demonstrated that indole-3-carbinol at concentrations of 20 μM and 100 μM significantly decreased expression of HDAC 3 by 2-fold and 3-fold in MIA cells, respectively. Results further showed that indole-3 carbinol decreased expression of HDAC 1 in CFPAC cells and HDAC 7 in BXPC cells by 2-fold. No change in expression was shown in any of the cell lines on HDAC 2. This study showed that indole-3-carbinol may exert histone deacetylase inhibitory effects. Further studies are needed to confirm these results. Specific HDACs as potential targets for pancreatic cancer are growing among the scientific community. HDACs are known to be regulators of growth, differentiation and cell death and dysfunction of transcriptional repression mediated by HDACs may lead to the development of cancer. Citation Format: Beverly D. Lyn-Cook, Li Pang, Lascelles E. Lyn-Cook, Beverly Word, George Hammons. Expression of histone deacetylases (HDACs) 1, 2, 3 and 7 in pancreatic cancer cell lines: The role of indole-3-carbinol. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5376. doi:10.1158/1538-7445.AM2013-5376

Detection ofTP53R249 Mutation in Iranian Patients with Pancreatic Cancer

The TP53 gene encodes tumor protein p53 which play a major role in the etiology of pancreatic cancer. The important role of codon 249 of TP53 for binding of p53 to its sequence-specific consensus site in DNA has been revealed by crystallography's studies, and mutation at this codon was detected in the plasma of some human cancers. The TP53 Mut assessor software within the International Agency for Research on Cancer (IARC) TP53 Database was performed to evaluate every possible mutation at codon 249. DNA was extracted from the plasma of 133 pancreatic cancer patients and 85 noncancer-bearing individuals. Exon 7 in TP53 was amplified, and mutation at R249 was identified by the endonuclease cleavage of HaeIII. The group of patients showed a frequency of 11% (22 of 133 samples) R249 mutation compared to 3.5% (3 of 85 samples) in the group of control which was significant (P = 0.03). This mutation demonstrated statistically significant association with pancreatic cancer risk in unadjusted odds ratio (OR: 3.74, 95% CI: 1.1–13.2; P = 0.041); however when adjusted for confounding factors, it was marginally significant because of lower control samples. These findings demonstrate that mutation at R249 of TP53 can be considered for increasing risk of pancreatic cancer that needs more research.

Insights into Pancreatic Cancer Etiology from Pathway Analysis of Genome-Wide Association Study Data

BackgroundPancreatic cancer is the fourth leading cause of cancer death in the U.S. and the etiology of this highly lethal disease has not been well defined. To identify genetic susceptibility factors for pancreatic cancer, we conducted pathway analysis of genome-wide association study (GWAS) data in 3,141 pancreatic cancer patients and 3,367 controls with European ancestry.MethodsUsing the gene set ridge regression in association studies (GRASS) method, we analyzed 197 pathways identified from the Kyoto Encyclopedia of Genes and Genomes database. We used the logistic kernel machine (LKM) test to identify major contributing genes to each pathway. We conducted functional enrichment analysis of the most significant genes (P<0.01) using the Database for Annotation, Visualization, and Integrated Discovery (DAVID).ResultsTwo pathways were significantly associated with risk of pancreatic cancer after adjusting for multiple comparisons (P<0.00025) and in replication testing: neuroactive ligand-receptor interaction, (Ps<0.00002), and the olfactory transduction pathway (P = 0.0001). LKM test identified four genes that were significantly associated with risk of pancreatic cancer after Bonferroni correction (P<1×10−5): ABO, HNF1A, OR13C4, and SHH. Functional enrichment analysis using DAVID consistently found the G protein-coupled receptor signaling pathway (including both neuroactive ligand-receptor interaction and olfactory transduction pathways) to be the most significant pathway for pancreatic cancer risk in this study population.ConclusionThese novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer.

Gene-Wide Association Study on the TERT Locus and PDAC Susceptibility. Results from the PANDoRA Consortium

Context SNPs in the telomerase reverse transcriptase ( TERT ) locus were reported to be associated with pancreatic cancer risk in a genome-wide association study (GWAS). TERT is essential for maintaining telomere ends. Its over-expression in normal cells can lead to prolonged cell lifespan and transformation. While telomerase activity cannot be detected in most normal tissues, it is seen in approximately 90% of human cancers. Objective We attempted to replicate and expand the association with the locus in a series of PDAC and healthy controls of European ancestry within the PANcreatic Disease ReseArch (PANDoRA) consortium. Methods We genotyped 13 SNPs in 1,034 PDAC cases and 2,443 controls from the PANDoRA consortium. We tested each SNP for association with PDAC risk and also with survival of the patients. Results We replicated the association reported in the GWAS with rs401681 (OR=1.53; 95%C;I 1.22-1.92; P=0.0002) and found a novel association between rs2736098 and decreased PDAC risk (OR=0.75; 95%CI: 0.63-0.88; P=0.001). Another polymorphism (rs4246742) was associated with worse survival (HR=1.75, 95%CI: 1.15-2.67; P=0.009). Conclusion We report here two novel findings: an association with risk (rs2736098) and one with survival of the patients (rs4246742). These results further contribute to our understanding in the genetic etiology of pancreatic cancer and suggest a new marker for disease prognosis.

Green tea drinking and risk of pancreatic cancer: A large-scale, population-based case–control study in urban Shanghai

Background: Little is known about the etiology of pancreatic cancer. Epidemiological studies on tea consumption and pancreatic cancer risk have been inconclusive. The purpose of the present study was to investigate the association between green tea drinking and the risk of pancreatic cancer in urban Shanghai, China. Methods: In this population-based case–control study conducted in urban Shanghai, 908 cases of pancreatic cancer and 1067 healthy controls were recruited. Information on tea drinking, including type of tea, amount of tea consumption, temperature of tea, and the duration of regular tea drinking, were collected via interview questionnaire. Results: We examined the association of multiple tea drinking habits with the risk of pancreatic cancer. In women, regular green tea drinking was associated with 32% reduction of pancreatic cancer risk (OR 0.68, 95% CI 0.48–0.96), compared to those who did not drink tea regularly. Increased consumption and longer duration of tea drinking were both associated with reduced pancreatic cancer risk in women. Among regular tea drinkers, lower temperature of tea was associated with reduced risk of pancreatic cancer in both men and women, independent of amount or duration of tea drinking. Conclusions: Habits of green tea drinking, including regular drinking, amount of consumption, persistence of the habit, and tea temperature, may lower pancreatic cancer risk.

MiR‐301a promotes pancreatic cancer cell proliferation by directly inhibiting bim expression

It is well known that microRNAs (miRNAs) play an important role in many diseases, including tumorigenesis. However, the mechanisms by which miRNAs regulate pancreatic cancer (PC) development remain poorly understood. In the present study, we assayed expression level of miR-301a in PC tissues by real-time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We first verified that the expression level of miR-301a was significantly increased in PC tissues. Moreover, miR-301a overexpression promoted PC cell proliferation, whereas its depletion decreased cell proliferation. We further demonstrated that miR-301a directly targeted 3'-UTR of Bim gene, and inhibited its protein expression in vitro and in vivo. Importantly, Bim re-expression reduced PC cell proliferation induced by miR-301a. These data suggest an important role of miR-301a in the molecular etiology of PC and implicate the potential application of miR-301a in PC therapy.

Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers

ObjectiveTo investigate whether the dietary antioxidants vitamins C and E, selenium and zinc decrease the risk of developing pancreatic cancer, for the first time using 7-day food diaries, the most...

N-3 fatty acids in the aetiology of pancreatic cancer. Data from a uk prospective cohort study using 7-day food diaries

s / Pancreatology 12 (2012) e1–e8 e3 Results: A total of 214 patients were identified. 62 patients underwent a CT scan and were thus eligible for inclusion. Visceral fat volume was the volumetric fat parameter with the most significant associationwith severe acute pancreatitis (p1⁄40.003). There was a significant association between visceral fat volume and subsequent development of systemic complications of severe acute pancreatitis (p1⁄40.003). There was a strong association between mortality and visceral fat volume (p1⁄40.019). Conclusion: Overall, CT volumetry indicates a strong association between visceral fat, severe acute pancreatitis and the subsequent development of systemic complications. This data suggests that visceral fat volume analysis should be incorporated into future predictive scoring systems. Take-home message: Visceral fat volume significantly contributes to the pro-inflammatory milieu experienced by patients with acute pancreatitis.

Abstract 1402: A xenograft pancreatic cancer mouse model to study the function of extracellular DNA in metastasis

Abstract Pancreatic cancer is one of the most lethal cancers with the lowest survival rate of all solid cancers. This is largely due to its highly aggressive metastasis, which almost always leads to death. Understanding the mechanisms and the process of pancreatic cancer metastasis is critical towards its prevention and treatments. Although the etiology of pancreatic cancer is not well understood, the relationship between inflammation and the development of this cancer has been well recognized. Extracellular DNA (exDNA) is a newly discovered component associated with inflammation. exDNA production can be induced by interleukin 8 (IL-8), one of the major inflammatory and angiogenic cytokine. IL-8 exhibits a significantly elevated level in pancreatic cancer cell lines MiaPaCa-2 and BxPC3 and has been shown to play a role in stimulating pancreatic tumorigenesis and metastasis. With this background, we initiated a study to examine the presence of exDNA associated with pancreatic cancer cells. We have discovered a large amount of extracellular DNA associated with cultured pancreatic cancer cells but not with the normal pancreatic cells. Here, we tested the hypothesis that pancreatic cancer cells produce extracellular DNA to promote their metastasis. Our in vitro study showed that removal of the exDNA by DNase I inhibited metastasis-associated characteristics of cancer cells including cell migration, invasion, and adhesion. To test our hypothesis in vivo, we generated the orthotopic xenograft pancreatic cancer mouse model. We used the pancreatic cancer cell line MiaPaCa-2/LucE expressing luciferase to induce tumors. We assessed the effect of DNase I treatment on pancreatic cancer metastasis from pancreases, the primary tumor site, to different organs. Tumors were examined directly in size and weight, and indirectly by the bioluminescent signal intensity that corresponds to the tumor size. Our preliminary data showed that continuous applications of a low dosage of DNase I reduced the tumor incidences and the tumor size measured by the chemiluminescence in all the organs examined. When mouse tumor tissues were stained with DAPI, a DNA-specific fluorescent dye and examined through immunohistochemistry (IHC) with DNA-specific antibody, high level of exDNA was found in the tumor tissues. More exDNA was found to be associated with the inflammatory area in the tumor tissues. We conclude that extracellular DNA play a novel role in metastatic behaviors of pancreatic cancer cells in vitro and facilitate metastasis in vivo. To our knowledge, this is the first report on the presence of exDNA associated with pancreatic cancer tissues and the first report on the inhibition of DNase I treatment on pancreatic cancer metastasis. Our results open new avenues for understanding the metastasis of pancreatic cancer, and facilitate the identification of new drug targets and development of new treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1402. doi:1538-7445.AM2012-1402

Fiber intake and pancreatic cancer risk: a case–control study

Scanty and inconsistent studies are available on the relation between dietary fiber intake and pancreatic cancer. A case-control study was carried out in northern Italy to further investigate the role of various types of dietary fibers in the etiology of pancreatic cancer. Cases were 326 patients with incident pancreatic cancer, excluding neuroendocrine tumors, admitted to major teaching and general hospitals during 1991-2008. Controls were 652 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for intake quintiles of different types of fiber after allowance for total energy intake and other potential confounding factors. Total fiber intake was inversely related to risk of pancreatic cancer (OR=0.4 for highest versus lowest quintile of intake; 95% CI 0.2-0.7). An inverse association emerged between pancreatic cancer and both soluble (OR=0.4; 95% CI 0.2-0.7) and total insoluble fiber (OR=0.5; 95% CI 0.3-0.8), particularly cellulose (OR=0.4; 95% CI 0.3-0.7) and lignin (OR=0.5; 95% CI 0.3-0.9). Fruit fiber intake was inversely associated with pancreatic cancer (OR=0.5; 95% CI 0.3-0.8), whereas grain fiber was not (OR=1.2; 95% CI 0.7-2.0). This study suggests that selected types of fiber and total fiber are inversely related to pancreatic cancer.

Pancreatic cancer risk and levels of trace elements

Background and AimsKnowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a...

MUC6 mucin expression inhibits tumor cell invasion

The MUC6 mucin has a critical protective function in the normal stomach, pancreas and duodenum and is aberrantly expressed during the progression of some gastrointestinal cancers. Our aim was to determine whether MUC6 contributes to the etiology or progression of pancreatic cancer and elucidate the molecular basis of its involvement. Expression of MUC6 glycoprotein was examined in pancreatic cancer tissues by immunofluorescence and loss of MUC6 was observed. Next, to determine whether MUC6 inhibits tumor growth and metastasis by altering cell adhesion and invasion, recombinant MUC6 cDNA and separate MUC6 N-terminal and C-terminal domains were transfected into pancreatic, colorectal and breast cancer cell lines. The recombinant N- and C-terminal proteins were each seen to oligomerize under non-reducing conditions. Overexpression of both domains of the MUC6 glycoprotein significantly inhibited cell adhesion to matrix proteins (collagen I, collagen IV, fibronectin and laminin) in LS 180 but not in PANC-1 cells. Moreover, the N- and C-terminal domains of MUC6 inhibited invasion of both LS 180 and PANC-1 cells by 40% and 70%, respectively, in comparison with controls. These results suggest that MUC6 may inhibit invasion of tumor cells through the basement membrane of the pancreatic duct and slow the development of infiltrating carcinoma.

Pancreatic cancer and diabetes mellitus: A retrospective cohort study.

4102 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States, with PC-related mortality of over 36,000 in 2010. The etiology of PC remains elusive. An association with diabetes mellitus (DM) has been suggested, but due to the inconsistencies of the epidemiologic studies addressing this association, a consensus has not been reached. Evidence is rising for hyperinsulinemia, which exists in Type II DM, as a risk factor for developing PC. We have studied the incidence of PC in two large cohorts of patients with and without Type II DM. Methods: This is a retrospective cohort study utilizing the health-care database maintained by the Veterans Integrated Services Network 16 (VISN16), which consists of 10 Veterans Health Administration (VHA) hospitals in the south-central USA. The two cohorts of the study consisted of a DM cohort of patients diagnosed with Type II DM between October 1st, 1996 and September 30th, 2006, and a control cohort of non-diabetics matched to DM patients by year of birth (YOB), gender, and VHA hospital. After 365 required cancer-free days on study, members of both cohorts were followed for the development of PC. Incidence during follow-up was compared between groups via stratified Cox regression with year of birth, gender, and VHA hospital as the stratification factors. Results: 322,614 subjects met inclusion criteria, including 110,919 DM subjects and 211,695 controls. Cohorts remained well-matched for gender (2.3% females in each) and YOB (medians of 1939 in each). The DM cohort had 124 PCs develop during 0.558 million person-years (MPY) of follow-up (222 PCs/MPY), whereas the control cohort had 140 PCs develop during 1.299 MPY of follow-up (108 PCs/MPY). Stratified Cox regression of PC incidence yielded a hazard ratio (95% CI) of 2.17 (1.70–2.77) for Type II DM compared to controls (chi-square =38.9, DF=1, P<10-9). Conclusions: This is one of the largest studies to examine the incidence of PC in patients with Type II DM. It shows a significantly higher incidence of PC in patients with DM. This study would provide a strong support for the etiologic role of DM II and hyperinsulinemia in the pathogenesis of PC.

Aspirin, NSAIDs, Calcium-Channel Blockers and Statins in the Aetiology of Pancreatic Cancer: Preliminary Results From a Case-Control Study in Two Centres in the UK

Introduction There are plausible mechanisms that carcinogenesis may be altered by: aspirin, NSAIDs, calcium-channel blockers and statins, through both inhibition of cyclo-oxygenase enzymes and the production of mediators of the cell cycle. The current epidemiological data in this area is either limited, reports conflicting results or does not consider important confounders. The aim of this study was to investigate whether there is a negative association between these medications and the development of pancreatic cancer in a case-control study in the UK. Methods Clinical management databases were used to identify patients diagnosed with pancreatic cancer managed in Norfolk (years 2004–2006) and Leicestershire (2007). The use of these medications, prior to diagnosis, was recorded from a detailed review of the medical records. The control group were 251 dermatology patients of similar ages treated for basal cell carcinoma. ORs with 95% CI, for the development of pancreatic cancer for each medication, were estimated using unconditional logistic regression and adjusted for gender, age at diagnosis, cigarette smoking and type II diabetes. Results A total of 206 cases of adenocarcinoma of the pancreas (median age=71 years, range 49–99 years, 52% women, a median survival of 3.5 months) and 251 controls were identified. Aspirin use was negatively associated with the development of pancreatic cancer (OR=0.49, 95% CI 0.29 to 0.84, p=0.01). There were no associations with either NSAIDs (OR=0.98, CI 0.50 to 1.91, p=0.95), statins (OR=0.64, CI 0.38 to 1.11, p=0.11) or calcium-channel blockers (OR=0.78, 95% CI 0.43 to 1.39, p=0.40). Conclusion The data support a protective role for aspirin, but not currently for the remaining medications in the aetiology of pancreatic cancer. The work is continuing to identify more cases and controls that may confirm our preliminary results for aspirin9s negative association and also show an effect for statins. Before aspirin can be recommended as a chemo-preventive agent, further population-based studies are required to confirm the association and provide detailed information on the dose of aspirin needed and its duration of use.

Physical Activity and the Risk of Developing Pancreatic Cancer – Data From a UK Prospective Study (EPIC-Norfolk)

Introduction Physical activity may reduce the risk of developing pancreatic cancer by preventing weight gain and improving glucose tolerance and insulin sensitivity. Previous epidemiological investigations of physical activity in large cohort studies have reported inconsistent results, although many showed no associations. The aim of this UK prospective cohort study was to investigate physical activity assessed by a questionnaire validated against detailed physiological measurements. Methods A total of 25 639 participants (56% women) aged 40–74 years were recruited into the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk). Participants attended a health check at enrolment where weight and height were recorded and they completed a questionnaire, which recorded occupational and recreational physical activity, which had been validated, firstly against energy expenditure (assessed by 4-day heart rate monitoring), and secondly cardio-respiratory fitness (assessed by sub-maximal oxygen uptake).From the questionnaire participants were classified into four groups of physical activity: active, moderately active, moderately inactive and inactive. The cohort was then monitored for 16 years and cancer registry data used to identify those who subsequently developed pancreatic cancer. A cohort analysis was performed using Cox regression modelling to estimate the hazard ratios (HR) for developing pancreatic cancer for each category of physical activity, adjusted for age, gender, smoking status, body mass index and diabetes. Results A total of 93 participants (52.6% women, mean age of diagnosis=72.2 years (SD=9.0 years)) developed pancreatic cancer with 77% having advanced disease. The interval between recruitment and diagnosis was 8.6 years (SD=3.7 years). No associations were found between increased physical activity and pancreatic cancer (active vs inactive HR=1.03, 95% CI 0.52 to 2.01, trend across categories HR=1.04 95% CI 0.84 to 1.28). Conclusion Physical activity was not associated with the risk of developing pancreatic cancer in a UK population, a result supported by most previous studies. The evidence is emerging that physical activity is not involved in the aetiology of pancreatic cancer.

Abstract 1872: A prospective cohort study of shift work and pancreatic cancer risk in Japanese men

Abstract The etiology of pancreatic cancer remains largely unknown. The lack of effective screening tools coupled with the dismal prognosis make it crucial to identify modifiable risk factors that can be incorporated into a prevention strategy for pancreatic cancer. Approximately 15-20% of the working population in industrialized countries engages in night-shift work, drawing considerable interest in the effect of such work patterns on health, including on the formation of cancers. We analyzed data from a large-scale, prospective cohort study of middle-aged and elderly Japanese individuals (the JACC Study) to test the hypothesis that rotating shift work might be associated with an increased risk of pancreatic cancer. Our analysis was restricted to 18,745 men who were 40-60 years of age at baseline (1988-1990) and who reported working full-time or were self-employed. Information on occupation and lifestyle factors was collected using a self-administered questionnaire. Mortality from pancreatic cancer was ascertained from the causes of death recorded on death certificates. The Cox proportional hazards model was used to estimate relative risk (RR) and confidence interval (CI) for the association between shift work and pancreatic cancer risk. A total of 70 pancreatic cancer deaths were observed until Dec 31, 2008. Overall, we found no statistically significant increase in the risk of death from pancreatic cancer associated with rotating shift work. As compared to day-shift workers, the RRs were 0.89 (95%CI: 0.40-1.96) for rotating shift workers and 0.27 (0.04-1.93) for fixed night-shift workers, after adjustment for potential confounding factors. In conclusion, shift work is not associated with the risk of death from pancreatic cancer in this cohort of Japanese men. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1872. doi:10.1158/1538-7445.AM2011-1872

Aspirin, NSAIDS, Calcium-channel blockers and statins in the aetiology of pancreatic cancer: preliminary results from a case-control study in two centres in the UK

IntroductionThere are plausible mechanisms that carcinogenesis may be altered by: aspirin, NSAIDs, calcium-channel blockers and statins, through both inhibition of cyclo-oxygenase enzymes and the production of mediators of the cell...

Physical activity and the risk of developing pancreatic cancer - data from a UK prospective study (EPIC-NORFOLK)

IntroductionPhysical activity may reduce the risk of developing pancreatic cancer by preventing weight gain and improving glucose tolerance and insulin sensitivity. Previous epidemiological investigations of physical activity in large cohort...

New Developments in Pancreatic Cancer

Pancreatic adenocarcinoma presents in an advanced stage and has a dismal prognosis. Extensive recent research efforts have provided us with greater insight into the etiology of pancreatic cancer and have also improved our means of prognostication. Molecular analysis demonstrated that specific pathways involved in pancreatic carcinogenesis are perhaps more valuable to study than single genetic aberrations. Previous risk factors, including family history, body mass index, and current cigarette smoking, were validated and novel risks, such as ABO blood group alleles, were identified. Similar to other illnesses, combinations of healthful habits, such as not smoking, adhering to a Mediterranean dietary pattern, and engaging in physical activity, may decrease pancreatic cancer risk. Finally, CA 19-9 levels, the presence of diabetes mellitus, and a six-gene signature provided critical information regarding survival that could help guide treatment of individuals diagnosed with pancreatic adenocarcinoma.

Superoxide Dismutase and Nicotinamide Adenine Dinucleotide Phosphate

Pancreatic carcinoma etiology and molecular pathogenesis is weakly understood. According to the assumption that genetic variation in carcinogen metabolism further modifies the risk of exposure-related cancers, an association of functional polymorphisms in oxidative stress-modifying genes superoxide dismutase 2 (SOD2 [Ala16Val, rs4880]), SOD3 (Arg231Gly, rs1799895), nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase (NQO1 [Pro187Ser, rs1800566], and NQO2 (Phe47Leu, rs1143684) with pancreatic cancer risk was studied. Polymorphisms were studied by allelic discrimination. In a hospital-based case-control study on 500 individuals (235 cases and 265 controls) of Czech white origin, SOD2, SOD3, NQO1, and NQO2 polymorphisms showed no significant association with pancreatic cancer risk. Major lifestyle factors such as smoking and alcohol, coffee, or tea consumption did not modify the effect of the studied polymorphisms. The first European study of the SOD2, SOD3, NQO1, and NQO2 roles in pancreatic cancer etiology did not find significant associations. Despite this observation, other populations with different lifestyle(s) may be at risk and should be further studied.