Higher Risk Of Pancreatic Cancer Research Articles

Survival benefit associated with screening of patients at elevated risk for pancreatic cancer.

All patients enrolled in screening at a High-Risk Pancreatic Cancer Clinic (HRC) from July 2013 to June 2020 were identified from a prospectively maintained institutional database and compared to patients evaluated at a Surgical Oncology Clinic (SOC) at the same institution during the same period. Clinical outcomes of patients selected for surgical resection, particularly clinicopathologic stage and overall survival, were compared. Among 826 HRC patients followed for a median (IQR) of 2.3 (0.8-4.2) years, 128 were selected for surgical resection and compared to 402 SOC patients selected for resection. Overall survival was significantly longer among HRC patients (median survival: not reached vs. 2.6 years, p < 0.001). Among 31 HRC and 217 SOC patients with a diagnosis of pancreatic ductal adenocarcinoma(PDAC), the majority of HRC patients were diagnosed with stage 0 disease (carcinoma in situ), while the majority of SOC patients were diagnosed with stage II disease (p < 0.001). Overall survival after resection of invasive PDAC was also significantly longer among HRC patients compared to SOC patients (median survival 5.5 vs. 1.6 years, p = 0.002). Patients at increased risk for PDAC and followed with guideline-based screening exhibited downstaging of disease and improved survival from PDAC in comparison to patients who were not screened.

Trends of pancreatic cancer-related mortality among patients with type 2 diabetes mellitus in the United States, 1999-2020.

e22523 Background: The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) is complex and bidirectional. While T2DM can be a risk factor for PC, pancreatic cancer can also lead to the onset or exacerbation of T2DM. Especially when these conditions coexist, individuals confront heightened mortality risks due to the compounded effects of both. Thus, our CDC analysis delves into mortality trends among patients affected by both conditions from “1999 to 2020”. By analyzing extensive datasets we scrutinized how factors such as gender, race, region of residence, and level of urbanization intersect with mortality rates. Our trend analysis highlights the need for effective strategies and interventions for individuals facing these complex health challenges simultaneously. Methods: We used the CDC Wonder database to analyze trends in PC-related mortality in patients with T2DM from 1999 to 2020. Age-adjusted mortality rate (AAMR) per 100,000 people with 95% confidence intervals was calculated for the total population, stratified by gender, race, urban/rural status, and census region. We used the Joinpoint regression software to calculate annual percentage change (APC) trend for each stratification. Results: In the US between 1999 and 2020, there were 20,980 deaths from PC in patients with T2DM. The overall AAMR showed a gradual rise from 0.15 per 100,000 in 1999 to 0.27 in 2008 (APC: 6.23), a relatively constant rate of 0.27 till 2013 (APC: -0.79), followed by a more recent sharp rise to 0.48 in 2020 (APC: 8.86). While both genders showed an increase in AAMR, men showed consistently higher AAMR than women in 1999 (AAMR Men: 0.20 vs Women: 0.12) and 2020 (AAMR Men: 0.60 vs Women: 0.37). Moreover, when stratified by race NH Blacks showed higher AAMR than NH Whites in 1999 (AAMR Black: 0.22 vs White: 0.14) and 2020 (AAMR Black: 0.51 vs White:0.48). Rural areas showed consistently higher AAMR than urban areas throughout the study period, from 1999 (AAMR Rural: 0.22 vs Urban: 0.14) till 2020 (AAMR Rural: 0.64 vs Urban:0.44). Finally, the highest mortality rate was observed in Western region (AAMR: 0.39), followed by the Midwestern region (AAMR: 0.36), Southern region (AAMR: 0.26), and Northeastern region (AAMR: 0.20). Conclusions: PC remains one of the leading causes of cancer-related deaths in developed high-income countries and despite the advancements in medicine, the median survival rate remains low. Considering the high risk of PC in patients with T2DM, it is imperative to devise regulations for regular screening to avoid delays in diagnosis and ensuing treatments. Our study underscores the need for larger population-based studies to further understand the primary factors influencing the observed geographical, racial, and gender disparities.

Circulating microRNAs in association with pancreatic cancer risk within 5 years.

Early detection is critical for improving pancreatic cancer prognosis. Our study aims to identify circulating microRNAs (miRNAs) associated with pancreatic cancer risk. The two-stage study used plasma samples collected ≤5 years prior to cancer diagnosis, from case-control studies nested in five prospective cohort studies. The discovery stage included 185 case-control pairs from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Replication stage samples comprised 277 pairs from Shanghai Women's Health Study/Shanghai Men's Health Study, Southern Community Cohort Study, and Multiethnic Cohort Study. Seven hundred and ninety-eight miRNAs were measured using the NanoString nCounter Analysis System. Odds ratios (OR) and 95% confidence intervals (CI) for per 10% change in miRNAs in association with pancreatic cancer risk were derived from conditional logistic regression analysis in discovery and replication studies, separately, and then meta-analyzed. Stratified analysis was conducted by age at diagnosis (<65/≥65 years) and time interval between sample collection and diagnosis (≤2/>2 years). In the discovery stage, 120 risk associated miRNAs were identified at p < .05. Three were validated in the replication stage: hsa-miR-199a-3p/hsa-miR-199b-3p, hsa-miR-767-5p, and hsa-miR-191-5p, with respective ORs (95% CI) being 0.89 (0.84-0.95), 1.08 (1.02-1.13), and 0.90 (0.85-0.95). Five additional miRNAs, hsa-miR-640, hsa-miR-874-5p, hsa-miR-1299, hsa-miR-22-3p, and hsa-miR-449b-5p, were validated among patients diagnosed at ≥65 years, with OR (95% CI) of 1.23 (1.09-1.39), 1.33 (1.16-1.52), 1.25 (1.09-1.43), 1.28 (1.12-1.46), 0.76 (0.65-0.89), and 1.22 (1.07-1.39), respectively. The miRNA targets were enriched in pancreatic carcinogenesis/progression-related pathways. Our study suggests that circulating miRNAs may identify individuals at high risk for pancreatic cancer ≤5 years prior to diagnosis, indicating its potential utility in cancer screening and surveillance.

A Simple Clinical Scoring System to Determine the Risk of Pancreatic Cancer in the General Population.

This study aimed to develop and validate a simple scoring system to determine the high-risk group for pancreatic cancer (PC) in the asymptomatic general population. The scoring system was developed using data from PC cases and randomly selected non-PC cases undergoing annual medical checkups between 2008 and 2013. The performance of this score was validated for participants with medical checkups between 2014 and 2016. In the development set, 45 PC cases were diagnosed and 450 non-PC cases were identified. Multivariate analysis showed three changes in clinical data from 1 year before diagnosis as independent risk factors: ΔHbA1c ≥ 0.3%, ΔBMI ≤ -0.5, and ΔLDL ≤ -20 mg/dL. A simple scoring system, incorporating variables and abdominal ultrasound findings, was developed. In the validation set, 36 PC cases were diagnosed over a 3-year period from 32,877 participants. The AUROC curve of the scoring system was 0.925 (95%CI 0.877-0.973). The positive score of early-stage PC cases, including Stage 0 and I cases, was significantly higher than that of non-PC cases (80% vs. 6%, p = 0.001). The simple scoring system effectively narrows down high-risk PC cases in the general population and provides a reasonable approach for early detection of PC.

IGF2BP2-related modification patterns in pancreatic cancer: A machine learning-driven approach towards personalized treatment

Pancreatic cancer (PC) is a malignant digestive system tumor with a very poor prognosis. N6-methyladenosine (m6A) is mediated by a variety of readers and participates in important regulatory roles in PC. Based on TCGA_PAAD, ICGC_AU_PAAD, ICGC_CA_PAAD, GSE28735 and GSE62452 datasets, We mapped the multi-omics changes of m6A readers in PC and found that m6A readers, especially IGF2BP family genes, had specific changes and were significantly associated with poor prognosis. An unsupervised consensus clustering algorithm was used to explore the correlation between specific expression patterns of m6A readers in PC and enrichment pathways, tumor immunity and clinical molecular subtypes. Then, the principal component analysis (PCA) algorithm was used to quantify specific expression patterns and screen core genes. Machine learning algorithms such as Bootstrapping and RSF were used to quantify the expression patterns of core genes and construct a prognostic scoring model for PC patients. What's more, pharmacogenomic databases were used to screen sensitive drug targets and small molecule compounds for high-risk PC patients in an all-around and multi-angle way. Our study has not only provided new insights into personalized prognostication approaches, but also thrown light on integrating tailored risk stratification with precision therapy based on IGF2BP2-mediated m6A modification patterns.

Correlation between main pancreatic duct diameter measurements: Special pancreatic ultrasonography versus magnetic resonance cholangiopancreatography.

Main pancreatic duct (MPD) dilatation is reported to be a risk factor for pancreatic cancer (PC). Although magnetic resonance cholangiopancreatography (MRCP) and ultrasonographic modalities are valuable for monitoring the pancreas, there is limited information on the efficacy of different imaging modalities in measuring MPD diameter. To improve pancreatic imaging, we developed a specialized ultrasound approach focusing on the pancreas (special pancreatic US). We aimed to examine the correlation between MPD diameter measurements using special pancreatic US versus MRCP. We retrospectively reviewed the clinical data of patients with MPD dilation (≥2.5 mm) via special pancreatic US used for screening at our institution between January 2020 and October 2022 and included patients who underwent magnetic resonance imaging 2 months before and after pancreatic US. The MPD diameter on MRCP was measured at the pancreatic locus, where the maximum MPD diameter was obtained on special pancreatic US. This study included 96 patients, with a median interval of 8.5 days between the date of special pancreatic US and the date of undergoing MRCP. MPD dilatation and/or pancreatic cysts were diagnosed in 86 patients, PC in 5 patients, and other diseases in 5 patients. The median MPD diameter, measured using special pancreatic US, was 3.4 mm (interquartile range: 2.9-4.9 mm), whereas it was 3.5 mm using MRCP (interquartile range: 2.8-4.5 mm). There were strong positive correlations between MPD diameter measured on special pancreatic US and that measured on MRCP (R = 0.925, P < .001). This study revealed strong positive correlations between the MPD diameter measurements using special pancreatic US and MRCP. MPD diameter measurements from each imaging method can be helpful during follow-up in individuals at a high risk of PC.

Identification and characterization of interferon-γ signaling-based personalized heterogeneity and therapeutic strategies in patients with pancreatic cancer.

Interferon-γ (IFN-γ) is a key cytokine with diverse biological functions, including antiviral defense, antitumor activity, immune regulation, and modulation of cellular processes. Nonetheless, its role in pancreatic cancer (PC) therapy remains debated. Therefore, it is worthwhile to explore the role of Interferon-γ related genes (IFN-γGs) in the progression of PC development. Transcriptomic data from 930 PC were sourced from TCGA, GEO, ICGC, and ArrayExpress, and 93 IFN-γGs were obtained from the MSigDB. We researched the characteristics of IFN-γGs in pan-cancer. Subsequently, the cohort of 930 PC was stratified into two distinct subgroups using the NMF algorithm. We then examined disparities in the activation of cancer-associated pathways within these subpopulations through GSVA analysis. We scrutinized immune infiltration in both subsets and probed classical molecular target drug sensitivity variations. Finally, we devised and validated a novel IFN-γ related prediction model using LASSO and Cox regression analyses. Furthermore, we conducted RT-qPCR and immunohistochemistry assays to validate the expression of seven target genes included in the prediction model. We demonstrated the CNV, SNV, methylation, expression levels, and prognostic characteristics of IFN-γGs in pan-cancers. Notably, Cluster 2 demonstrated superior prognostic outcomes and heightened immune cell infiltration compared to Clusters 1. We also assessed the IC50 values of classical molecular targeted drugs to establish links between IFN-γGs expression levels and drug responsiveness. Additionally, by applying our prediction model, we segregated PC patients into high-risk and low-risk groups, identifying potential benefits of cisplatin, docetaxel, pazopanib, midostaurin, epothilone.B, thapsigargin, bryostatin.1, and AICAR for high-risk PC patients, and metformin, roscovitine, salubrinal, and cyclopamine for those in the low-risk group. The expression levels of these model genes were further verified through HPA website data and qRT-PCR assays in PC cell lines and tissues. This study unveils IFN-γGs related molecular subsets in pancreatic cancer for the first time, shedding light on the pivotal role of IFN-γGs in the progression of PC. Furthermore, we establish an IFN-γGs related prognostic model for predicting the survival of PC, offering a theoretical foundation for exploring the precise mechanisms of IFN-γGs in PC.

Gallstones, cholecystectomy and the risk of pancreatic cancer: an updated systematic review and meta-analysis of cohort studies.

The effect of gallstones and cholecystectomy on the development of pancreatic cancer has recently prompted many population-based studies. However, the results are controversial. We conducted an updated systematic review and meta-analysis to explore the causality among gallstones, cholecystectomy and pancreatic cancer. Cohort studies published in the PubMed, Web of Science, Embase, and Cochrane Library databases up to May 2023 were retrieved. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were analyzed using a random-effects model. We screened 1391 articles and included 16 studies. Gallstones were not associated with an increased risk of pancreatic cancer ( P = 0.082), with only the Asian population ( P = 0.011) showing an increased risk in the subgroup analysis. A markedly higher risk of pancreatic cancer was observed among patients with cholecystectomy (RR = 1.23; 95% CI, 1.07-1.41; P = 0.004; I 2 = 74.4%). The association remained significant in the Asian population ( P = 0.004), in the subgroup analyses stratified by sex, lag period, and time interval since cholecystectomy, and when the models were adjusted for diabetes, smoking, and BMI. Interestingly, cholecystectomy due to gallstones (RR = 1.30; 95% CI, 1.14-1.48; P < 0.001; I 2 = 30.8%), rather than for unspecified reasons ( P = 0.116), markedly increased the risk of pancreatic cancer. In conclusion, cholecystectomy due to gallstones, rather than gallstone formation, conferred an increased risk for pancreatic cancer. There was a higher risk for the Asian population for both gallstones and cholecystectomy.

Validation of a real-time biliopancreatic endoscopic ultrasonography analytical device in China: a prospective, single-centre, randomised, controlled trial

Endoscopic ultrasonography (EUS) is a key procedure for the diagnosis of biliopancreatic diseases. However, the performance among EUS endoscopists varies greatly and leads to blind spots during the operation, which can impair the health outcomes of patients. We previously developed an artificial intelligence (AI) device that accurately identified EUS standard stations and significantly reduced the difficulty of ultrasonography image interpretation. In this study, we updated the device (named EUS-IREAD) and validated its performance in improving the quality of EUS procedures. In this single-centre, randomised, controlled trial, we updated EUS-IREAD so it consisted of five learning models to identify eight EUS stations and 24 anatomical structures. The trial was done at the Renmin Hospital of Wuhan University (Wuhan, China) and included patients aged 18 years or older with suspected biliopancreatic (pancreas and biliopancreatic duct) lesions due to clinical symptoms, radiological findings, or laboratory findings, and with a high risk of pancreatic cancer. Patients were randomly assigned (1:1) by a dedicated research assistant using a computer-generated random number series (with a block size of four) to undergo the EUS procedure with or without the assistance of EUS-IREAD. Endoscopists in the EUS-IREAD-assisted group were required to observe all standard stations and anatomical structures according to the prompts by the AI device. Data collectors, the independent data anaylsis team, and patients were masked to group allocation. The primary outcome was the missed scanning rate of standard stations between the two groups, which was assessed in patients who underwent EUS procedure in accordance with the assigned intervention (per protocol). This trial is registered with ClinicalTrials.gov, NCT05457101. Between July 9, 2022, and Feb 28, 2023, 290 patients (mean age 55·93 years [SD 14·06], 152 [52%] male, and 138 [48%] female) were randomly assigned and analysed, including 144 in the EUS-IREAD-assisted group and 146 in the control group. The EUS-IREAD-assisted group had a lower missed scanning rate of stations than the control group (4·5% [SD 0·8] vs 14·3% [1·0], -9·8% [95% CI -12·2 to -7·5]; odds ratio 3·6 [95% Cl 2·6 to 4·9]; p<0·0001). No significant adverse event was found during the study. Our study confirms the capability of EUS-IREAD to monitor the blind spots and reduce the missed rate of stations and structures during EUS procedures. The EUS-IREAD has the potential to play an essential part in EUS quality control. Innovation Team Project of Health Commission of Hubei Province and College-enterprise Deepening Reform Project of Wuhan University.

Epidemiology of pancreatic cancer

At present, pancreatic cancer morbidity continues to grow at an accelerated rate worldwide. At the same time the five-year survival rate of patients with pancreatic cancer remains low, occupying a significant position in the mortality structure. This is mainly due to late diagnosis, as well as to the increasing proportion of the elderly population. Factors influencing the prognosis include age, sex, blood group, family history and genetic predisposition, diabetes, smoking, alcohol, chronic pancreatitis, and obesity. Objective: to present up-to-date data on pancreatic cancer epidemiology in the world, Russian Federation and Omsk region. Materials and methods: the article analyzes the data of morbidity, mortality and five-year survival rate of patients with pancreatic cancer for the years 2020-2021. Results: the growth of morbidity and persistent low survival rates emphasize the necessity of determining methods of screening patients with high risk of pancreatic cancer, developing methods of early detection and improving both surgical and drug treatment of these patients, as well as prophylaxis.

Immunohistochemical, pharmacovigilance, and omics analyses reveal the involvement of ATP-sensitive K+ channel subunits in cancers: role in drug-disease interactions.

Background: ATP-sensitive-K+ channels (KATP) are involved in diseases, but their role in cancer is poorly described. Pituitary macroadenoma has been observed in Cantu' syndrome (C.S.), which is associated with the gain-of-function mutations of the ABCC9 and KCNJ8 genes. We tested the role of the ABCC8/Sur1, ABCC9/Sur2A/B, KCNJ11/Kir6.2, and KCNJ8/Kir6.1 genes experimentally in a minoxidil-induced renal tumor in male rats and in the female canine breast cancer, a spontaneous animal model of disease, and in the pharmacovigilance and omics databases. Methods: We performed biopsies from renal tissues of male rats (N = 5) following a sub-chronic high dosing topical administration of minoxidil (0.777-77.7mg/kg/day) and from breast tissues of female dogs for diagnosis (N = 23) that were analyzed by immunohistochemistry. Pharmacovigilance and omics data were extracted from EudraVigilance and omics databases, respectively. Results: An elevated immunohistochemical reactivity to Sur2A-mAb was detected in the cytosol of the Ki67+/G3 cells other than in the surface membrane in the minoxidil-induced renal tumor and the breast tumor samples. KCNJ11, KCNJ8, and ABCC9 genes are upregulated in cancers but ABCC8 is downregulated. The Kir6.2-Sur2A/B-channel opener minoxidil showed 23 case reports of breast cancer and one case of ovarian cancer in line with omics data reporting, respectively, and the negative and positive prognostic roles of the ABCC9 gene in these cancers. Sulfonylureas and glinides blocking the pancreatic Kir6.2-Sur1 subunits showed a higher risk for pancreatic cancer in line with the positive prognostic role of the ABCC8 gene but low risks for common cancers. Glibenclamide, repaglinide, and glimepiride show a lower cancer risk within the KATP channel blockers. The Kir6.2-Sur1 opener diazoxide shows no cancer reactions. Conclusion: An elevated expression of the Sur2A subunit was found in proliferating cells in two animal models of cancer. Immunohistochemistry/omics/pharmacovigilance data reveal the role of the Kir6.1/2-Sur2A/B subunits as a drug target in breast/renal cancers and in C.S.

Metformin inhibits neutrophil extracellular traps-promoted pancreatic carcinogenesis in obese mice

Obesity has been linked to a higher risk of pancreatic cancer. However, the mechanism by which obesity promote pancreatic carcinogenesis is still unclear. We investigated the effect of obesity on pancreatic carcinogenesis in Pdx1-Cre; LSL-KrasG12D+/− (KC) mice. Metformin was administrated to rescue the effects of obesity and NETs. The pro-tumorigenic effects of neutrophil extracellular traps (NETs) were further evaluated in vivo and vitro. We found that obesity significantly promoted the progression of murine pancreatic ductal intraepithelial neoplasia (mPanIN). The proliferation rate and epithelial-mesenchymal transition (EMT) of mPanIN ductal cells were increased in obese mice. More visceral adipocytes, PD-L1+ neutrophil infiltration and NETs formation were found in the pancreas of obese mice and visceral adipocytes could recruit neutrophils and promote NETs formation. The latter could induce an inflammatory response in ductal cells via TLR4-dependent pathways both in vivo and vitro, as demonstrated by upregulation of IL-1β. Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro. Our study provides causal evidence for the contribution of obesity in promoting pancreatic carcinogenesis in genetic model and reveals the mechanism by NETs to regulate mPanIN progression.

Dietary sugar consumption and health: umbrella review

ObjectiveTo evaluate the quality of evidence, potential biases, and validity of all available studies on dietary sugar consumption and health outcomes.DesignUmbrella review of existing meta-analyses.Data sourcesPubMed, Embase, Web of Science,...

Prospective characterization of oral and gut microbiome in a high-risk pancreatic cancer cohort.

691 Background: Pancreatic cancer (PC) is the third leading cause of cancer death in the United States. The high mortality associated with PC is attributed to multiple reasons: lack of effective therapies, aggressive biology and late diagnosis. Due to the absence of reliable early disease biomarkers, PC screening is largely dependent on imaging. Recent studies have highlighted the importance of the gut and tumor microbiome in PC. We present here the first report of oral and gut microbiome prospective analysis of PC high-risk individuals (PC-HRI) undergoing screening. Methods: We collected periodontal and stool samples at the University of Texas MD Anderson Cancer Center from 2017-2022. A total of 448 samples, consisting of 250 oral and 198 gut samples were obtained. Samples were collected from PC (n=73), PC-HRI (n=34), and healthy (n=143) individuals. 16s rRNA sequencing was used to characterize the oral and gut microbiome and statistical analysis and correlation with imaging and clinical characteristics were performed. Results: We identified three phyla, namely Proteobacteria, Actinobacteria, and Fusobacteria as significantly more abundant in the gut microbiome of PC patients. Conversely, Proteobacteria was decreased in the oral microbiome of PC patients. At the class level, Gammaproteobacteria (GP) oral/gut ratio was significantly decreased in PC patients compared with healthy individuals (p=0.02). Analysis of PC-HRI revealed also low GP oral/gut ratio in high-risk individuals who were diagnosed with worrisome pancreatic focal lesions. Interestingly, Gammaproteobacteria (GP) is one of the main classes of bacteria detected in pancreatic cancer tissue. GP shifts in oral and gut environments could be implicated in pancreatic early tumorigenesis and serve as biomarker of the disease. Additionally, gut bacteria with metabolic pathways related to lipid metabolism were more enriched in PC patients and PC-HRI with focal lesions compared to healthy controls. Conclusions: Gammaproteobacteria oral/gut ratio represents a potential novel biomarker which could predict presence of early high risk-pancreatic focal lesions in PC-HRI. Taken together, this report provides observational evidence about changes in oral and gut microbiome in patients with pancreatic cancer but even more importantly, the fact that those changes could be detected in PC-HRI with early high-risk lesions. Broader validation in other high-risk cohorts would be required. Detection of GP oral/gut ratio would represent an inexpensive, non-invasive method that could be useful for PC screening. Functional studies should be performed to determine how GP shifts can contribute with pancreatic tumorigenesis. Research supported by CPRIT (Grant Number: RP200173) and philanthropic funding through the MD Anderson Moonshot Program.

Pancreatic Cancer in Celiac Disease Patients-A Systematic Review and Meta-Analysis.

Background: Celiac disease (CD) is an autoimmune enteropathy affecting approximately 1% of the population and is associated with an increased risk of enteropathy-associated T-cell lymphoma and small bowel adenocarcinoma, whereas the association between CD and other malignancies is unclear. Since pancreatic cancer (PC) remains one of the most lethal neoplasms and its incidence is increasing despite numerous ongoing research on diagnostic biomarkers and novel therapies, we aimed to investigate whether CD has an impact on the risk of PC. Material and Methods: We performed a systematic review of the literature published from January 2000 to March 2022 in two databases: Web of Science and Scopus and a meta-analysis of eligible studies. Results: Our search identified eight publications included in the systematic review. A total of five studies involving 47,941 patients, including 6399 CD patients with malignancies and 1231 PC cases were included in the meta-analysis and 221 cases of PC in CD patients with other cancers were recognized. The pooled OR for PC was 1.46 (95% CI 1.26−1.7) with significant heterogeneity (89.1%; p < 0.05), suggesting that CD patients with malignancies were at higher risk for PC. Conclusions: The association between CD and PC is uncertain. However, the results of the current meta-analysis may indicate an increased risk of PC in the group of patients with CD and other cancers. Further multicenter studies are warranted.

Cuproptosis-related LncRNAs signature as biomarker of prognosis and immune infiltration in pancreatic cancer.

Background: Pancreatic cancer (PC) is a malignant gastrointestinal tumor with a terrible prognosis. Cuproptosis is a recently discovered form of cell death. This study is intended to explore the relationship between cuproptosis-related lncRNAs (CRLncs) signature with the prognosis and the tumor microenvironment (TME) of PC. Methods: Transcript sequencing data of PC samples with clinical information were obtained from the Cancer Genome Atlas (TCGA). Univariate Cox regression analysis and LASSO regression analysis were employed to construct the prognostic signature based on CRLncs associated with PC survival. A nomogram was created according to this signature, and the signaling pathway enrichment was analyzed. Subsequently, we explored the link between this prognostic signature with the mutational landscape and TME. Eventually, drug sensitivity was predicted based on this signature. Results: Forty-six of 159 CRLncs were most significantly relevant to the prognosis of PC, and a 6-lncRNA prognostic signature was established. The expression level of signature lncRNAs were detected in PC cell lines. The AUC value of the ROC curve for this risk score predicting 5-year survival in PC was .944, which was an independent prognostic factor for PC. The risk score was tightly related to the mutational pattern of PC, especially the driver genes of PC. Single-sample gene set enrichment analysis (ssGSEA) demonstrated a significant correlation between signature with the TME of PC. Ultimately, compounds were measured for therapy in high-risk and low-risk PC patients, respectively. Conclusion: A prognostic signature of CRLncs for PC was established in the current study, which may serve as a promising marker for the outcomes of PC patients and has important forecasting roles for gene mutations, immune cell infiltration, and drug sensitivity in PC.

Diabetes Mellitus and Pancreatic Cancer: Investigation of Causal Pathways Through Mendelian Randomization Analysis

Abstract Objective: This study was aimed at investigating the association between diabetes mellitus and susceptibility to pancreatic cancer by using Mendelian randomization (MR) methods and an extensive human genome-wide association study (GWAS) dataset. Methods: The publicly accessible MR Base database was used to obtain the complete genome, relevant research findings, and summary data pertaining to diabetes mellitus and pancreatic cancer. Genetic variables, specifically single-nucleotide polymorphisms closely associated with diabetes mellitus, were selected for analysis. Four methods—inverse variance weighted (IVW) analysis, weighted median analysis, weighted mode, and MR-Egger regression—were used. Statistical analysis was conducted to explore the potential association between diabetes mellitus and susceptibility to pancreatic cancer. Results: The results of the IVW analysis (OR = 11.56519319, 95% CI 1.275068624–104.8992116, P = 0.0296) indicated a significant causal relationship between diabetes and elevated pancreatitis risk. Furthermore, the absence of horizontal pleiotropic effects (Egger intercept = 0.29, P = 0.384) and heterogeneity (P = 0.126) suggested that the observed association was not influenced by confounding factors. Sensitivity analysis and other statistical methods also supported the conclusion that genetic pleiotropy did not introduce bias to the findings. Conclusion: A causal relationship exists between diabetes mellitus and the occurrence of pancreatic cancer. People with diabetes mellitus are at high risk of pancreatic cancer and should receive early screening. The IGF signaling pathway may be a key mediator of the effects of diabetes on pancreatic cancer pathogenesis.

Pancreatitis and Pancreatic Cancer Risk.

Purpose: The present retrospective study aimed to explore the relationship between pancreatitis and pancreatic cancer in the population cohort of the UK Biobank (UKB) (https://www.ukbiobank.ac.uk). Methods: From the 500 thousand population cohort of UKB, according to the age and gender of patients with pancreatic cancer 1:10, matching the control without pancreatic cancer, the binary Logistic regression model was used to analyze the relationship between pancreatitis and pancreatic cancer, and subgroup analyses were used to identify potential effect modifiers. Results: A total of 1538 patients with pancreatic cancer were compared with 15 380 controls. In the fully adjusted model, patients with pancreatitis had a significantly increased risk of pancreatic cancer compared with no pancreatitis. The risk of pancreatitis and pancreatic cancer increased with the age of pancreatitis, and the risk of pancreatic cancer was highest in the 61 to 70 age group. In addition, in the first 3 years of acute pancreatitis, the risk of pancreatic cancer increased significantly with the increase in the duration of the disease (odds ratio [OR] 29.13, 95% confidence interval [CI]: 16.34-51.93), after 3 years, the trend of increase decreased. After more than 10 years, there was no significant correlation between the risk of acute pancreatitis and pancreatic cancer. However, patients with chronic pancreatitis were significantly associated with an increased risk of pancreatic cancer only in the first 3 years (OR 28.14, 95% CI: 14.86-53.31). Conclusion: Pancreatitis may associate with an increased risk of pancreatic cancer. The older the age of pancreatitis, the higher the risk of pancreatic cancer. The risk of pancreatic cancer increases significantly in the first 3 years of the course of pancreatitis. This may provide an alternative strategy for the early identification of individuals at high risk of pancreatic cancer.

Circulating gamma-glutamyl transpeptidase and risk of pancreatic cancer: A prospective cohort study in the UK Biobank.

To determine whether serum gamma-glutamyl transpeptidase (GGT) level is associated with pancreatic cancer risk in a large prospective cohort. The study analyzed serum GGT concentration at baseline of 421,032 participants recruited in the UK Biobank since 2006 through 2010. Information on incidence of pancreatic cancer was obtained from cancer and death registers, updated until 2015 in Scotland or 2016 in England and Wales. Adjusted Cox proportional hazards models were used to measure the association between serum GGTand pancreatic cancer risk. The study identified 586 cases of pancreatic cancer over a median follow-up period of 7.16 years. In the multivariable-adjusted Cox model, serum GGT level was associated with 14% higher pancreatic cancer risk (hazard ratio (HR) per one standard deviation increment of log2 GGT level=1.14, 95% confidence interval (CI) 1.02-1.28, p= 0.025). In the total population, the HR for the highest GGT group was 1.68 (95%CI: 1.22-2.30) versus the lowest GGT group. The HR for the highest GGT group in men (≥50.2U/L) was 1.72 (95%CI: 1.14-2.61) and that in women (≥31.6U/L) was 1.75 (95%CI: 1.06-2.88) versus the lowest GGT group. Our findings suggested a positive association of serum GGT in pancreatic cancer etiology, implying the potential of monitoring GGT level for identifying at-risk individuals for pancreatic cancer.

Difference of Risk of Pancreatic Cancer in New-Onset Diabetes and Long-standing Diabetes: A Population-based Cohort Study.

Considering the absence of methods to find pancreatic cancer early, surveillance of high-risk groups is needed for early diagnosis. The study aimed to investigate the effect in the incidence of pancreatic cancer and the differences between new-onset diabetes mellitus (NODM) and long-standing DM (LSDM) since NODM group is a representative high-risk group. The Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013 data were used. Regarding 88 396 people with DM (case group), we conducted a 1:1 propensity score matching to select a matched non-DM population (control group). To investigate the interaction between DM and the time variable distinguishing NODM and LSDM, we performed a multivariate time-dependent Cox regression analysis. The incidence of pancreatic cancer was higher in the DM group compared to the non-DM group (0.52% vs 0.16%; P < .001). The DM group had shown different risk of pancreatic cancer development according to the duration since the DM diagnosis (NODM hazard ratio (HR): 3.81; 95% CI, 2.97-4.88; P < .001; LSDM HR: 1.53; 95% CI, 1.11-2.11; P < .001). When the NODM and the LSDM groups were compared, the risk of pancreatic cancer was higher in the NODM group than in the LSDM group (HR: 1.55; P = .020). In subgroup analysis, NODM group showed that men (HR = 4.42; 95% CI, 3.15-6.19; P < .001) and patients who were in their 50 seconds (HR = 7.54; 95% CI, 3.24-17.56; P < .001) were at a higher risk of developing pancreatic cancer than matched same sex or age control group (non-DM population), respectively. The risk of pancreatic cancer was greater in people with DM than in a non-DM population. Among people with DM, NODM showed a higher risk of pancreatic cancer than LSDM.