Risk Factor For Chronic Pancreatitis Research Articles

Pancreatitis-Diabetes-Pancreatic Cancer

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article.

Gastric Mucosal Calcinosis: A Rare Cause of Bleeding

A52-year-old man with end-stage renal disease on hemodialysis presented with coffee-ground emesis and black stools. The physical examination revealed pale conjunctivae but was otherwise unremarkable. The laboratory analysis was significant for hemoglobin 4.4 g/dL, creatinine 7.8 mg/dL, and normal calcium and phosphorus (8.7 mg/dL and 2.5 mg/dL, respectively). The esophagogastroduodenoscopy revealed multiple smooth, nonbleeding nodules measuring 3–5 mm in diameter, extending radially in linear rows throughout the antrumwith an overlying clot (Figure A). Two similar lesions were noted in the second portion of the duodenum (Figure B). Biopsies showed benign gastric and small bowel mucosa with calcinosis (Figure C). The bone scan demonstrated radiotracer within the region of the stomach, also compatible with calcinosis. The computed tomography scan was significant for mitral annular calcification and scattered pancreatic parenchymal calcifications. The patient did not have any risk factors for chronic pancreatitis. A review of laboratory studies over the past year revealed a persistently elevated parathyroid hormone as well as frequent hyperphosphatemia with occasional hypercalcemia. Two sessions of argon plasma coagulation, 14 days apart, were performed on the gastric lesions. No other endoscopic therapy was undertaken. After 8 months of follow-up, the patient did not have further bleeding. Gastric mucosal calcinosis (GMC) is a rare disorder typically encountered incidentally on routine biopsy or at autopsy. Metastatic calcification is the most common cause of GMC and occurs in the setting of abnormal calcium-phosphate metabolism. Hypercalcemia and/or hyperphosphatemia cause the deposition of calcium salts

Role of tobacco as compared with alcohol in the activation of pro-inflammatory factors and cytokine release from pancreatic acinar cells

s / Pancreatology such as organ failure, necrosis, and mortality. The amount of fluid over the first 24-48 hours needed to be provided. When combining the various studies, the weighted mean of power (sample size) was used to determine the relative value of significance. Sensitivity analysis evaluated sample sizes, timing, type of fluids and severity of patients included. Ten published studies fulfilled the criteria to be included in the analysis, which included 1495 patients. There were 6 retrospective, 4 prospective studies. While 3 studies concluded that aggressive hydration was beneficial, 7 studies showed no benefit and/or harm. Using a weighted mean analysis, when evaluating the effectiveness of aggressive intravenous hydration beyond 24 hours, there was no significant difference in the development of organ failure, pancreatic necrosis or mortality (OR 1.2, CI 0.4 -1.9). However, in a subgroup analysis excluding patients presenting with severe disease, there was a significant benefit to aggressive intravenous hydration in preventing organ failure and/or pancreatic necrosis (OR 1.8, CI 1.5 -2.8, p 1⁄4 0.02). Additionally, there was a significant decrease in organ failure and/or pancreatic necrosis if the aggressive intravenous hydration was given early, within the first 24 hours (OR 2.1, CI 1.6 – 2.9, p1⁄4 0.03) and 6-12 hours (p 1⁄4 0.02). Based on this meta-analysis, aggressive intravenous hydration appears to be most beneficial when applied to patients with acute pancreatitis early in the course of the disease, within the first 6-24 hours, before severe disease develops. In general, there does not appear to be a benefit to aggressive hydration in patients with acute pancreatitis beyond the first 24 hours. Clinicians should recognize the importance of applying the principles of aggressive hydration as early as possible, especially to patients who have mild disease. The benefit of early aggressive hydration appears to be preventing severe disease, organ failure and/or pancreatic necrosis. O-14 Abstract id: 189. Role of tobacco as compared with alcohol in the activation of pro-inflammatory factors and cytokine release from pancreatic acinar cells Maria Luaces-Regueira , Margarita Casti~ neira-Alvari~ no , Julio IglesiasGarcia , Jos e Lari~ no-Noia , J. Enrique Dominguez-Mu~ noz . 1 Foundation for Research In Digestive Diseases, Spain University Hopital of Santiago de Compostela. Foundation for Research in Digestive Diseases, Spain Introduction: Triggering of the inflammatory process through the activation of pro-inflammatory transcription factors, as NFkappaB, and secretion of pro-inflammatory cytokines is a central pathogenic mechanism of chronic pancreatitis (CP). Previous studies suggest a role for alcohol in this inflammatory process, but the effect of tobacco, which is a recognized risk factor for CP, is unknown. Aims: To analyse the effect of tobacco compared with alcohol in the activation of pro-inflammatory factors and cytokine release from pancreatic acinar cells in culture. Materials & methods: Pancreatic acinar cells were isolated from Swiss mouse pancreas by enzymatic (collagenase) and mechanic degradation, filtration and centrifugation. Cells were stimulated over 3 hours with cholecystokinin (CCK, positive control), alcohol (at 10,25,50,75,100 mM) and tobacco (at 0.001,0.01,0.1,0.2,0.4 mg/ml). NFkappaB activation (translocation of the subunit p65 into the nucleus) was measured by Western blot. Interleukin-1b secretionwas analyzed by ELISA in cellular supernatant. Data are shown as mean and standard error, and analyzed by ANOVA test. Results: Tobacco, but not alcohol, induces activation of NFKappaB (2.69þ1.05 fold increase of p65 translocation at 0.1 mg/ml over the negative control). Neither tobacco nor alcohol induces interleukin-1b release, ranging between 14.1 1.1 pg/ml (negative control) to 20.1 3.6 pg/ml (tobacco 0.1 mg/ml), and to 23.8 9.2 pg/ml (ethanol 100 mM) (n.s.). Conclusion: Tobacco, but not alcohol, initiates the inflammatory process through the activation of NFKappaB in acinar cells. By this mechanism, tobacco can act as a pathogenic factor in chronic pancreatitis. O-15 Abstract id: 248. Serotonin mediates pancreatic acinar cell cytoskeletal remodeling in mice Enrica Saponara, Sabrina Sonda, Kamil e Grabliauskaite, Theresia

Su1315 Etiology and Risk Factors for Chronic Pancreatitis (CP) in the United States: A Report of the North American Pancreas Study (NAPS2) Group

Su1315 Etiology and Risk Factors for Chronic Pancreatitis (CP) in the United States: A Report of the North American Pancreas Study (NAPS2) Group

The Epidemiology of Pancreatitis and Pancreatic Cancer

Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer.

Smoking and Pancreatic Disease

Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.

Obesity and Pancreatic Diseases

Obesity is defined as BMI (calculated as weight in kg divided by height in m2) more than 30, and overweight is defined as BMI of 25-29.9. Obesity has been considered as a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Severe acute pancreatitis is significantly more frequent in obese patients. Furthermore, obese patients develop systemic and local complications of acute pancreatitis more frequently. The underlying mechanisms are increased inflammation and necrosis from increased amount of intra- and peri-pancreatic fat. In addition, obesity is a poor prognostic factor in acute pancreatitis, and overweight before disease onset appears to be a risk factor for chronic pancreatitis. Overweight and/or obesity are associated with greater risk of pancreatic cancer and younger age of onset. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight. Long-standing diabetes increases the risk of pancreatic cancer. The pathogenic mechanism is that obesity and physical inactivity increase insulin resistance. In a state of hypersinulinemia, increased circulating level of insulin-like growth factor-1 induces cellular proliferation of pancreatic cancer. Obesity is associated with negative prognostic factor and increased mortality in pancreatic cancer. However, there are controversies regarding the effects of obesity on long-term post-operative results in the patient with pancreatic cancer.

PRSS1 intron mutations in patients with pancreatic cancer and chronic pancreatitis

Genetic risk factors of chronic pancreatitis (CP) have been identified and a number of studies have found that CP can lead to pancreatic cancer. Therefore, the detection of pancreatitis-associated gene mutations can aid the pancreatic cancer diagnostic process. Mutations in three genes, the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the pancreatic secretory trypsin inhibitor (SPINK1) gene, have been identified as risk factors for CP. The aim of this study was to describe specific novel mutations in the intron of the PRSS1 gene in patients with pancreatic cancer and CP. A total of 65 unrelated patients with pancreatic cancer and 29 with CP were reviewed. Mutations and polymorphisms of the PRSS1 gene were analyzed by direct sequencing. Information regarding clinical data and smoking exposure was collected by personal interviews using a structured questionnaire. IVS 3+36 A>G mutation in the PRSS1 gene was found in 2 cases with pancreatic cancer, and these 2 patients were classified as never-smokers. IVS 3+127 T>A and IVS 3+157 G>C double mutations were identified in one patient with CP. All patients were found to have serum trypsin levels lower than that of the normal controls. Therefore, the PRSS1 gene mutation may be a special common cause of pancreatic cancer and CP.

Is smoking a risk factor for acute pancreatitis?

Smoking is known to be a risk factor for chronic pancreatitis. However, to date, few studies have investigated the association between smoking and the risk of acute pancreatitis. A recent prospective, population-based study provides strong evidence that smoking should be considered a risk factor for acute pancreatitis.

Smoking Is Underrecognized as a Risk Factor for Chronic Pancreatitis

Background/Aims: Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor. Methods: We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject's self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor. Results: Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor. Conclusions: Physicians often underrecognize smoking as a CP riskfactor. Efforts are needed to raise awareness of the association between smoking and CP.

Alcohol and Smoking as Risk Factors in an Epidemiology Study of Patients With Chronic Pancreatitis

Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP.

M1372 Smoking is Under Appreciated as a Risk Factor for Chronic Pancreatitis

Background: Despite data showing an independent association between smoking and chronic pancreatitis (CP), it is unclear how often physicians consider smoking as a CP risk factor. Aim: Identify how often and in which patients physicians identify smoking as a CP risk factor. Methods: We analyzed data on CP patients (n = 535) prospectively enrolled in the multicenter North American Pancreatitis Study 2 (NAPS2). Patient self-reported smoking status was stratified as never, past, or current, and the amount and duration of smoking was quantified. For each patient, we noted whether the enrolling physician classified alcohol as the diagnostic etiology for CP and whether or not smoking was selected as a risk factor. Results: Among 382 (71.4%) self-reported past or current smokers, physicians cited smoking as a risk factor in only 173 (45.3%) patients, more often when they considered alcohol as CP etiology (54.5 vs. 32.5%, p<0.001). Among patients considered to have alcohol as an etiology, physicians identified smoking as a risk factor equally irrespective of the status (current vs. past) (55.4 vs. 51.1%, p= NS) or the amount of smoking. Among patients not classified as having an alcohol etiology, physicians were more likely to cite smoking as a risk factor in current rather than past smokers (47.4% vs. 19.0%, p<0.001) and in patients who reported higher amount and duration of smoking. Although patient's self-reported smoking status was generally similar across participating centers, a wide variability in physician decision to cite smoking as a risk factor was observed (Figure 1). On multivariable regression analyses however, the association between smoking and CP was independent of physician's decision to cite smoking as a risk factor. Conclusions: Cigarette smoking is common in CP patients. Physicians often underestimate smoking as a CP risk factor. Efforts are needed to increase awareness of the association between smoking and CP.

M1374 Epidemiology of Chronic Pancreatitis (CP) at U.S. Referral Centers: Data From the North American Pancreatitis Study 2 (Naps2)

Background: Despite data showing an independent association between smoking and chronic pancreatitis (CP), it is unclear how often physicians consider smoking as a CP risk factor. Aim: Identify how often and in which patients physicians identify smoking as a CP risk factor. Methods: We analyzed data on CP patients (n = 535) prospectively enrolled in the multicenter North American Pancreatitis Study 2 (NAPS2). Patient self-reported smoking status was stratified as never, past, or current, and the amount and duration of smoking was quantified. For each patient, we noted whether the enrolling physician classified alcohol as the diagnostic etiology for CP and whether or not smoking was selected as a risk factor. Results: Among 382 (71.4%) self-reported past or current smokers, physicians cited smoking as a risk factor in only 173 (45.3%) patients, more often when they considered alcohol as CP etiology (54.5 vs. 32.5%, p<0.001). Among patients considered to have alcohol as an etiology, physicians identified smoking as a risk factor equally irrespective of the status (current vs. past) (55.4 vs. 51.1%, p= NS) or the amount of smoking. Among patients not classified as having an alcohol etiology, physicians were more likely to cite smoking as a risk factor in current rather than past smokers (47.4% vs. 19.0%, p<0.001) and in patients who reported higher amount and duration of smoking. Although patient's self-reported smoking status was generally similar across participating centers, a wide variability in physician decision to cite smoking as a risk factor was observed (Figure 1). On multivariable regression analyses however, the association between smoking and CP was independent of physician's decision to cite smoking as a risk factor. Conclusions: Cigarette smoking is common in CP patients. Physicians often underestimate smoking as a CP risk factor. Efforts are needed to increase awareness of the association between smoking and CP.

Alcohol Consumption, Cigarette Smoking, and the Risk of Recurrent Acute and Chronic Pancreatitis

Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are associated with alcohol consumption and cigarette smoking. The etiology of RAP and CP is complex, and effects of alcohol and smoking may be limited to specific patient subsets. We examined the current prevalence of alcohol use and smoking and their association with RAP and CP in patients evaluated at US referral centers. The North American Pancreatitis Study 2, a multicenter consortium of 20 US centers, prospectively enrolled 540 patients with CP, 460 patients with RAP, and 695 controls from 2000 to 2006. Using self-reported monthly alcohol consumption during the maximum lifetime drinking period, we classified subjects by drinking status: abstainer, light drinker (< or =0.5 drink per day), moderate drinker (women, >0.5 to 1 drink per day; men, >0.5 to 2 drinks per day), heavy drinker (women, >1 to <5 drinks per day; men, >2 to <5 drinks per day), or very heavy drinker (> or =5 drinks per day for both sexes). Smoking was classified as never, past, or current and was quantified (packs per day and pack-years). Overall, participants' mean (SD) age was 49.7 (15.4) years; 87.5% were white, and 56.5% were women. Approximately one-fourth of both controls and patients were lifetime abstainers. The prevalence of very heavy drinking among men and women was 38.4% and 11.0% for CP, 16.9% and 5.5% for RAP, and 10.0% and 3.6% for controls. Compared with abstaining and light drinking, very heavy drinking was significantly associated with CP (odds ratio, 3.10; 95% confidence interval, 1.87-5.14) after controlling for age, sex, smoking status, and body mass index. Cigarette smoking was an independent, dose-dependent risk factor for CP and RAP. Very heavy alcohol consumption and smoking are independent risks for CP. A minority of patients with pancreatitis currently seen at US referral centers report very heavy drinking.

Etiology of chronic pancreatitis: Has it changed in the last decade?

The evidence from recent surveys on chronic pancreatitis carried out around the world shows that alcohol remains the main factor associated with chronic pancreatitis, even if at a frequency lower than that reported previously. It has further confirmed that heavy alcohol consumption and smoking are independent risk factors for chronic pancreatitis. Autoimmune pancreatitis accounts for 2%-4% of all forms of chronic pancreatitis, but this frequency will probably increase over the next few years. The rise in idiopathic chronic pancreatitis, especially in India, represents a black hole in recently published surveys. Despite the progress made so far regarding the possibility of establishing the hereditary forms of chronic pancreatitis and the recognition of autoimmune pancreatitis, it is possible that we are more inaccurate today than in the past in identifying the factors associated with chronic pancreatitis in our patients.

Chronic pancreatitis: Report from a multicenter Italian survey (PanCroInfAISP) on 893 patients

No data on chronic pancreatitis in Italy are available yet. To evaluate demographic, clinical, diagnostic and therapeutic aspects in patients suffering from chronic pancreatitis. Eligible patients were prospectively enrolled from 2000 to 2005. Information concerning demographic data, lifestyle risk factors, family and clinical history, associated factors (alcohol, autoimmunity, cystic dystrophy of the duodenal wall, obstruction, genetic mutations) concomitant diseases, diagnostic findings, and pharmacological, endoscopic and surgical therapy were gathered. 893 patients (74% males, mean age 53.7+/-15.2 years) were evaluated. 519/859 patients (60%) were drinkers and 555/840 (66%) were smokers. A strong positive correlation between drinking and cigarette consumption (R=0.53; p<0.0001) was found. Heavy alcohol consumption (>80g of alcohol/day for more than 5 years) was considered the most important risk factor in 300 patients (34%), obstruction in 238 (27%), alcohol and obstruction in 82 (9%), autoimmunity in 34 (4%), cystic dystrophy of the duodenal wall/groove pancreatitis in 55 (6%), gene mutations in 36 (4%), and none (idiopathic) in 148 (17%). Bile stones were diagnosed in 287 patients (33%) and cholecystectomy was performed in 329 patients (38%). Pancreatic calcifications were diagnosed in 547/879 patients (62%). Pancreatic surgery was performed in 273 patients (31%). Endoscopic sphincterotomy was performed in 371 patients (42%). Exocrine and endocrine insufficiency were found, respectively, in 373/834 (45%) and 275/885 patients (31%). An unexpected low frequency of alcohol abuse and new emerging associated risk factors for chronic pancreatitis were observed in Italy.

Genetic risk factors in chronic pancreatitis

Chronic pancreatitis is a persistent inflammatory disorder of the pancreas, characterized by destruction of the pancreatic parenchyma, maldigestion, chronic pain and diabetes mellitus. Genetic factors determining susceptibility to chronic pancreatitis can be classified in two groups: 1. rare gene mutations affecting the cationic trypsinogen gene that directly cause the disease, and 2. genetic variants that increase the risk for chronic pancreatitis but require additional risk factors to precipitate the disease. These gene variants are considered genetic risk factors, which emerged during the past decade and now represent a clinically important etiological category. Susceptibility to chronic pancreatitis is inherited in a complex manner, which can involve alterations in several genes conferring various degrees of risk. The biochemical mechanism behind the genetic risk includes increased ectopic activation of the digestive enzyme trypsin in the pancreas and failure of protective mechanisms responsible for trypsin inactivation.

MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma

Chronic pancreatitis and pancreatic adenocarcinoma are extensively studied as common and potentially lethal disorders. However, their causes and genetic background in most cases remain unclear. The C677T polymorphism in 5',10'-methylenetetrahydrofolate reductase (MTHFR) gene may modulate the risk of pancreatic disorders. In this study, we tested whether MTHFR C677T polymorphism is associated with chronic pancreatitis and pancreatic adenocarcinoma in the Serbian population. DNA was extracted from blood samples of 51 chronic pancreatitis patients, 21 pancreatic adenocarcinoma patients, and a control group consisting of 50 healthy smokers. The MTHFR C677T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Although, no statistically significant differences were observed in the distribution of MTHFR genotype or allele frequencies between patients and control groups, the results showed an increased frequency of homozygotes for MTHFR C677T polymorphism in chronic pancreatitis patients (14%) and a decreased frequency in pancreatic adenocarcinoma patients (5%) in comparison to the control group (8%). We speculate that the MTHFR C677T polymorphism could act as a possible risk factor for chronic pancreatitis and a possible protective factor in pancreatic adenocarcinoma. This observation needs further investigation in prospective studies on a larger number of patients, in which the effect of other genetic and environmental factors should also be taken into consideration.

A novel A121T mutation in human cationic trypsinogen associated with hereditary pancreatitis: functional data indicating a loss-of-function mutation influencing the R122 trypsin cleavage site

Background:The understanding of genetic risk factors for chronic pancreatitis increased in the last decade with the discovery of mutations in the cationic trypsinogen gene (PRSS1). The first mutation was detected...

Microsatellite Scan Identifies New Candidate Genes for Susceptibility to Alcoholic Chronic Pancreatitis in Japanese Patients

Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years) and 99 healthy Japanese controls were enrolled in this study. This was an association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. This search revealed 10 candidate susceptibility regions and 5 candidate resistant regions throughout the genome. No specific microsatellite markers were detected in association with previously reported susceptibility genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007 on chromosome 15q14 showed strong evidence for disease susceptibility (70.8% vs. 35.1%, Pc = 0.0001). Within 500 kb of D15S1007, several genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281, LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and 5 candidate resistant regions that may contain genes involved in ACP pathogenesis.