Pancreatic injury, genetic variation of PNPLA3, and risk of pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 141-141
Author(s):  
Mohammed Aly ◽  
Ibrahim Halil Sahin ◽  
Donghui Li ◽  
Mohamed Fahd Khalil ◽  
Ping Chang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Cancer ◽  
Fatty Liver ◽  
Genetic Susceptibility ◽  
Fatty Infiltration ◽  
A Genome ◽  
Increased Risk ◽  
History Of ◽  
History Of Obesity ◽  
Pancreatic Steatosis

141 Background: Similar to primary liver cancer, obesity, diabetes mellitus and hepatitis B virus infection have been associated with increased risk of pancreatic cancer (PC) development. A genome-wide association study has reported that a polymorphic variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene was associated with a higher susceptibility to fatty liver and liver cancer. The relationship between this variation and PC has not been previously examined. We investigated the correlation in the degree of organ damage between the liver and the pancreas in patients with PC. In addition, we examined the effect of PNPLA3genetic variation (rs738409: C>G) on PC development. Methods: Using resources of our case-control study in MD Anderson Cancer Center, we analyzed 544 pathologically confirmed PC patients and 498 healthy controls. Cases and controls were frequency matched by age, gender, and race. Multivariate logistic regression analysis was performed to adjust for the confounding factors. Medical records of PC patients were reviewed for pancreatic and liver fatty changes. Results: We found that 18.8% of PC patients had evidence of pancreatic steatosis, fibrosis, or pancreatitis. Fatty liver was observed in 14.5% of PC patients which was frequently detected in patients with pancreatitis (p=0.002). A significant correlation between pancreatitis and cirrhosis was observed in PC patients with a prior history of obesity but not in patients without a history of obesity (p=0.001). On the other hand, we observed no significant association between PNPLA3 genotype and risk of PC. The adjusted odds ratio (OR) was 1.4 (95% confidence interval [CI], 0.7-2.7) for the homozygous variant GG genotype compared with the CC/CG genotypes. Conclusions: We concluded that despite the similarities between the liver and the pancreas, genetic susceptibility to fatty infiltration and its effect on cancer development may differ between the two organs. Evaluation and assessment of nonalcoholic fatty pancreatic disease (NAFPD) in PC patients and genetic susceptibility of NAFPD may be warranted in future research.

Extended evidence for association between the melanoma inhibitory activity 3 gene and myocardial infarction

2011 ◽  
Vol 105 (04) ◽  
pp. 670-675 ◽  
Author(s):  
Anna Schatke ◽  
Hannah Wolferstetter ◽  
Jakob Mueller ◽  
Albert Schömig ◽  
Adnan Kastrati ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inhibitory Activity ◽  
Chromosome 1 ◽  
Nucleotide Polymorphisms ◽  
Current Cigarette Smoking ◽  
A Genome ◽  
Increased Risk ◽  
Melanoma Inhibitory Activity ◽  
History Of ◽  
The Impact

SummaryIn a genome-wide scan, isolated single nucleotide polymorphisms (SNPs), including rs17465637, in the melanoma inhibitory activity 3 gene (MIA3) on chromosome 1 were identified to be associated with coronary artery disease and myocardial infarction (MI). Because the role of common variation at the MIA3 locus has not yet been investigated, the aim of this case-control study was to determine the impact of haplotype-tagging SNPs and haplotypes in the MIA3 region on the risk of MI. In a set of nine haplotype-tagging SNPs, rs17465637, but none of the other SNPs, was associated with MI. After adjustments were made for age, gender, history of arterial hypertension, history of hyper-cholesterolaemia, current cigarette smoking and diabetes mellitus, multiple logistic regression analyses showed an increased risk in the carriers of one or two C alleles [adjusted odds ratio (OR) 1.17, 95% confidence interval (CI) 1.04–1.32, and 1.37, 95% CI 1.08–1.74, respectively]. Nine common haplotypes (frequency >1%) were established across the MIA3 region. Two of the haplotypes were associated with an increased risk of MI: the frequent (48%) TGACCAAAG haplotype and the rare (2%) CGACCAAAG haplotype (adjusted OR 1.102, 95% CI 1.002–1.212, and 1.574, 95% CI 1.077–2.298, respectively). Showing association between rs17465637 and MI, this work was consistent with results from the original detection study and most prior replication studies addressing this issue. In addition to correspond with such isolated evidence of association with MI, the present study identified specific haplotypes capturing the risk-related variation in the entire MIA3 region.

scholarly journals Study of the Association between Hypothyroidism and Non-Alcoholic Fatty Liver Disease

2019 ◽  
Vol 9 (5-s) ◽  
pp. 4-6
Author(s):  
Anoop Uniyal ◽  
Prashant Mathur ◽  
Yogesh Joshi
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Data Gathering ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Significant Difference ◽  
History Of ◽  
Thyroid Profile ◽  
Alcoholic Fatty Liver Disease

Aim: The aim of the present study was to investigate the association between hypothyroidism and non-alcoholic fatty liver disease (NAFLD). Methods: In a prospective observational study, the hypothyroidism patients were evaluated for NAFLD using ultrasonography. The participant’s characteristics such as age, gender, thyroid profile, history of diabetes, hypertension, ischemic heart disease (IHD) were recorded using a data gathering form. Results: A total of 51 participants were included in this study. From 51 participants, 47 (92.18%) individuals were females whereas 4 (7.82%) individuals were males. Out of 51 participants 27 individuals had NAFLD. There was statistically significant difference in FT4 levels with the participants with NAFLD. Conclusion: Results from this study suggested that low FT4 concentration is associated with increased risk of NAFLD. Keywords: Hypothyroidism, NAFLD, ultrasonography, FT4.

Association of fatty pancreas with increased risk of pancreatic adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16729-e16729
Author(s):  
Bara El Kurdi ◽  
Adam Bataineh ◽  
Sumbal Babar ◽  
Mahmoud El Iskandarani ◽  
Mohammad Alomari ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Pancreatitis ◽  
Family History ◽  
Pancreatic Adenocarcinoma ◽  
Meta Analysis ◽  
Fatty Infiltration ◽  
Diagnostic Approach ◽  
Increased Risk ◽  
History Of ◽  
Meta Regression

e16729 Background: Pancreatic adenocarcinoma (PADC) remains one of the most fatal malignancies with poor outcomes and prognosis. Several risk factors have been associated with its development such as smoking, age, obesity, chronic pancreatitis, diabetes mellitus and a family history of PADC. Furthermore, recent pathologic studies demonstrated that fatty infiltration of the pancreas (FP) is positively correlated with PADC development. We sought to systematically review the literature and perform the first meta-analysis to study the risk of PADC among patients with FP. Methods: We conducted a systematic search of the Pubmed, EMBASE, and Cochrane databases from inception through November-2019 for studies correlating FP with PADC. Relevant data was extracted and analyzed using comprehensive meta-analysis software. Random-effects model was used for all variables. Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic. Publication bias was assessed using Egger’s test. Meta regression models accounting for independent variables such as age, sex, smoking, family history of PADC, chronic pancreatitis and method of FP diagnosis were constructed to explain heterogeneity. Results: Five observational case-control studies published between 2014 and 2019 including a total of 761 patients (320 PADC patients and 441 controls) were included. FP was associated with increased PADC with an OR 4.6 (CI 2.4-8.9) compared to controls with a considerable heterogeneity (I2= 69%). Meta regression analysis accounting for modality used to diagnose FP was able to explain 100% of the noted heterogeneity. Conclusions: While we noted FP to be significantly associated with increased PADC, heterogeneity in FP diagnostic approach resulted in significant inter-study variation. A consensus on a clear definition of FP with a standardized diagnostic approach is needed to better appraise literature on this emerging disease entity. Further prospective studies are needed to validate our results and explore the possible role for PADC screening in FP in addition to known factors such as family history and new-onset diabetes mellitus.

Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion

2019 ◽  
Vol 37 (2) ◽  
pp. 153-164 ◽  
Author(s):  
Elena M. Stoffel ◽  
Shannon E. McKernin ◽  
Randall Brand ◽  
Marcia Canto ◽  
Michael Goggins ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Adenocarcinoma ◽  
Health Care Providers ◽  
Expert Panel ◽  
Familial Pancreatic Cancer ◽  
Care Providers ◽  
Increased Risk ◽  
History Of

Purpose An ASCO provisional clinical opinion (PCO) offers timely clinical direction to ASCO’s membership and other health care providers. This PCO addresses identification and management of patients and family members with possible predisposition to pancreatic adenocarcinoma. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature published from January 1998 to June 2018. Results of the databases searched were supplemented with hand searching of the bibliographies of systematic reviews and selected seminal articles and contributions from Expert Panel members’ curated files. Provisional Clinical Opinion All patients diagnosed with pancreatic adenocarcinoma should undergo assessment of risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma. Assessment of risk should include a comprehensive review of family history of cancer. Individuals with a family history of pancreatic cancer affecting two first-degree relatives meet criteria for familial pancreatic cancer (FPC). Individuals (cancer affected or unaffected) with a family history of pancreatic cancer meeting criteria for FPC, those with three or more diagnoses of pancreatic cancer in same side of the family, and individuals meeting criteria for other genetic syndromes associated with increased risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates for genetic testing. Germline genetic testing for cancer susceptibility may be discussed with individuals diagnosed with pancreatic cancer, even if family history is unremarkable. Benefits and limitations of pancreatic cancer screening should be discussed with individuals whose family history meets criteria for FPC and/or genetic susceptibility to pancreatic cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

scholarly journals Intrahepatic Cholangiocarcinoma Masquerading as Acute Fatty Liver of Pregnancy: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Ayman Qasrawi ◽  
Omar Abughanimeh ◽  
Mouhanna Abu Ghanimeh ◽  
Simran Arora-Elder ◽  
Osama Yousef ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Intrahepatic Cholangiocarcinoma ◽  
Fatty Infiltration ◽  
Signs And Symptoms ◽  
Gastrointestinal Malignancies ◽  
History Of ◽  
Acute Fatty Liver ◽  
Laboratory Investigations ◽  
Upper Abdominal ◽  
Elevated Transaminases

Cholangiocarcinoma (CCA) is an uncommon cancer and accounts only for 3% of all gastrointestinal malignancies. In this report, we present a case of an intrahepatic cholangiocarcinoma masquerading as acute fatty liver of pregnancy (AFLP). A 38-year-old female who is 36-week pregnant presented with a 1-week history of headache, nausea, vomiting, and right upper abdominal pain, along with hepatomegaly. Laboratory investigations were remarkable for mild leukocytosis, hyperbilirubinemia, proteinuria, and elevated transaminases and prothrombin time. Ultrasound of the liver revealed hepatomegaly, fatty infiltration, and a right hepatic lobe mass. Based on the overall picture, AFLP was suspected, and the patient underwent delivery by Cesarean section. However, bilirubin and liver enzyme levels gradually increased after delivery. MRI revealed a large dominant hepatic mass along with multiple satellite lesions in both lobes. Biopsy revealed the presence of intrahepatic CCA. CCA presenting during pregnancy is extremely rare with only 9 other cases reported in the literature. Therefore, the signs and symptoms can be easily confused with other more common disorders that occur during pregnancy.

scholarly journals Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

2019 ◽  
Vol 55 (4) ◽  
pp. 453-461 ◽  
Author(s):  
Nele Brusselaers ◽  
Omid Sadr-Azodi ◽  
Lars Engstrand
Keyword(s):  
Pancreatic Cancer ◽  
Receptor Antagonist ◽  
Proton Pump ◽  
Population Based ◽  
H2 Receptor Antagonist ◽  
H2 Receptor ◽  
Increased Risk ◽  
History Of ◽  
Rate Ratios

Abstract Background The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among long-term PPI users in Sweden. Methods This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison. Results Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12–2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90, 95% CI 4.26–16.37), and among individuals with a history of Helicobacter pylori (SIR = 2.99, 95% CI 2.54–3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38–1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66–1.51). Conclusions This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users.

ATM mutation carriers and family history of pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1529-1529
Author(s):  
Jeannie Klavanian ◽  
Dana Zakalik ◽  
Anish S Konde ◽  
Tara Rangarajan
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Gene Mutations ◽  
Close Relative ◽  
Degree Relative ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Age Of Diagnosis ◽  
History Of ◽  
Atm Gene

1529 Background: Multigene panel testing (MGT) is commonly utilized in patients with a personal or family history of cancer. One of the more common gene mutations identified is in the ATM gene, associated with a moderately increased risk of breast and other cancers. There are reports of an association with pancreatic cancer, however the exact risks are unclear. The aim of this study is to describe the family history of pancreatic cancer in a cohort of ATM mutation carriers, and to evaluate possible genotype/phenotype correlation. Methods: Patients who underwent MGT, between ‘13 and ‘19, and tested positive for a pathogenic/likely pathogenic ATM mutation were included in this study. Family history, with a focus on pancreatic cancer, and genetic testing results were analyzed. Results: A total of 114 patients were identified to carry an ATM mutation. Twenty-two (19.3%) individuals had a family history of pancreatic cancer in a close relative, and of those, 13 (11.4%) had an affected first degree relative, and 11 (9.6%) had an affected second degree relative. Among the families with pancreatic cancer, 20 close relatives had a personal history of pancreatic cancer, with the youngest diagnosed at age 40, the oldest diagnosed at age 91, and a mean age of diagnosis of 66.5 years. Thirteen unique variants were identified: 4 splice site, 3 missense, 3 frameshift, 1 nonsense, and 1 silent. Two families had the known high-penetrance ATM mutation, c.7271T > C (p.V2424G). Conclusions: This study describes the association of pancreatic cancer in individuals found to carry pathogenic ATM mutations. A significant proportion (19.3%) of patients had a family history of pancreatic cancer in a close relative, diagnosed as young as age 40. The mean age of diagnosis was slightly younger than the average age in the general population (age 70). As pancreatic cancer screening continues to improve, this information will be an important component to help guide cancer risk assessment and future screening recommendations for ATM mutation carriers. Additional larger studies are needed to further characterize pancreatic cancer risks in patients with ATM gene mutations.

Mendelian Randomization Analysis Dissects the Relationship between NAFLD, T2D, and Obesity and Provides Implications to Precision Medicine

2019 ◽  
Author(s):  
Zhipeng Liu ◽  
Yang Zhang ◽  
Sarah Graham ◽  
Roger Pique-Regi ◽  
Xiaocheng Charlie Dong ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Total Cholesterol ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Central Obesity ◽  
Mendelian Randomization ◽  
Alcoholic Fatty Liver ◽  
A Genome ◽  
Increased Risk

ABSTRACTBackgroundNon-alcoholic fatty liver disease (NAFLD) is epidemiologically correlated with both type 2 diabetes (T2D) and obesity. However, the causal inter-relationships among the three diseases have not been completely investigated.AimWe aim to explore the causal relationships among the three diseases.Design and methodsWe performed a genome-wide association study (GWAS) on fatty liver disease in ∼400,000 UK BioBank samples. Using this data as well as the largest-to-date publicly available summary-level GWAS data, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis. This analysis tested the causal inter-relationship between NAFLD, T2D, and obesity, as well as the association between genetically driven NAFLD (with two well-established SNPs at the PNPLA3 and TM6SF2 loci) and glycemic and lipidemic traits, respectively. Transgenic mice expressing the human PNPLA3 I148I (TghPNPLA3-I148I) and PNPLA3 I148M (TghPNPLA3-I148M) isoforms were used to further validate the causal effects.ResultsWe found that genetically instrumented hepatic steatosis significantly increased the risk for T2D (OR=1.3, 95% CI: [1.2, 1.4],p=8.3e-14) but not the intermediate glycemic phenotypes at the Bonferroni-adjusted level of significance (p<0.002). There was a moderate, but significant causal association between genetically driven hepatic steatosis and decreased risk for BMI (β=- 0.027 SD, 95%CI: [−0.043, −0.01],p=1.3e-4), but an increased risk for WHRadjBMI (Waist-Hip Ratio adjusted for BMI) (β=0.039 SD, 95%CI: [0.023, 0.054],p=8.2e-7), as well as a decreased level for total cholesterol (β=-0.084 SD, 95%CI [−0.13, −0.036],p=6.8e-4), but not triglycerides (β=0.02 SD, 95%CI [−0.023, 0.062],p=0.36). The reverse MR analyses suggested that genetically driven T2D (OR=1.1, 95% CI: [1.0, 1.2],p=1.7e-3), BMI (OR=2.3, 95% CI: [2.0, 2.7],p=1.4e-25) and WHRadjBMI (OR=1.5, 95% CI: [1.3, 1.8],p=1.1e-6) causally increase the NAFLD risk. In the animal study, as compared to the TghPNPLA3-I148I controls, the TghPNPLA3-I148M mice developed higher fasting glucose level and reduced glucose clearance. Meanwhile, the TghPNPLA3-I148M mice demonstrated a reduced body weight, increased central to peripheral fat ratio, decreased circulating total cholesterol as compared to the TghPNPLA3-I148I controls.ConclusionThis large-scale bidirectional MR study suggests that lifelong, genetically driven NAFLD is a causal risk factor for T2D (hence potentially a “NAFLD-driven T2D” subtype) and central obesity (or “NAFLD-driven obesity” subtype), but protects against overall obesity; while genetically driven T2D, obesity, and central obesity also causally increase the risk of NAFLD, hence a “metabolic NAFLD”. This causal relationship revealed new insights into disease subtypes and provided novel hypotheses for precision treatment or prevention for the three diseases.

scholarly journals Family History of Cancer and Tobacco Exposure in Index Cases of Pancreatic Ductal Adenocarcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
R. Lochan ◽  
A. K. Daly ◽  
H. L. Reeves ◽  
R. M. Charnley
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pancreatic Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Tobacco Exposure ◽  
Degree Relative ◽  
Family History Questionnaire ◽  
Increased Risk ◽  
History Of ◽  
History Of Cancer

Aim. To examine interaction between history of cancer in first-degree relatives and tobacco smoking in index patients of pancreatic adenocarcinoma.Methods. We carried out a case-control involving 113 patients with pancreatic adenocarcinoma and 110 controls over a 12-month period at the Freeman Hospital, Newcastle upon Tyne, UK. They were all administered a detailed tobacco exposure questionnaire and a family history questionnaire. We calculated cumulative tobacco exposure and risk for pancreas cancer.Results. Both smokers (OR 3.01 (95% CI: 1.73 to 5.24)) and those with a family history of malignancy (OR 1.98 (95% CI: 1.15–3.38)) were more likely to develop pancreatic cancer. Having more than one first-degree relative with cancer did not significantly further increase the risk of pancreatic cancer. Amongst pancreatic cancer cases, cumulative tobacco exposure was significantly decreased () in the group of smokers (current and ex-smokers) who had a family history of malignancy [mean (SD): 30.00 (24.77) pack-years versus 44.69 (28.47) pack-years with no such history].Conclusions. Individuals with a family history of malignancy are at an increased risk of pancreatic cancer. Furthermore, individuals with a family history of malignancy and who smoke appear to require a lesser degree of tobacco exposure for the development of pancreatic cancer.

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