Pancreatic Cancer Mortality Research Articles

US Cancer Mortality Trends Among Asian and Pacific Islander Populations

Cancer is the leading cause of death among Asian American individuals and the second leading cause of death among Native Hawaiian and Pacific Islander people. To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Asian American and Pacific Islander populations in the US by demographic characteristics. This cross-sectional study used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to obtain age-adjusted cancer death rates among Asian American and Pacific Islander individuals of all ages between January 1, 1999, and December 31, 2020. Data were analyzed from January 12 to March 19, 2024. Age, sex, cancer type, and US census regions. Trends and average annual percent changes (AAPCs) in age-adjusted cancer-specific mortality (CSM) rates for non-Hispanic Asian American and Pacific Islander populations were estimated by cancer type, age, sex, and region using Joinpoint regression. Between 1999 and 2020, 305 386 Asian American and Pacific Islander individuals (median [IQR] age, 69.5 [58.5-79.2] years; 51.1% male) died of cancer in the US. Overall, the CSM rate decreased by 1.5% annually. Men experienced a greater CSM rate decrease (AAPC, -1.8%; 95% CI, -2.2% to -1.3%) compared with women (AAPC, -1.1%; 95% CI: -1.2% to -1.0%). For women, death rates decreased for most cancer types but increased for uterine (AAPC, 2.5%; 95% CI, 2.0%-3.0%) and brain and central nervous system (AAPC, 1.4%; 95% CI: 0.7%-2.1%) cancers. Colorectal cancer mortality rates increased among men aged 45 to 54 years (AAPC, 1.3%; 95% CI, 0.5%-2.1%). Liver and intrahepatic bile duct cancer mortality increased for both men and women in all US census regions, uterine cancer mortality increased in all regions for women, and pancreatic cancer mortality increased in the Midwest for both men and women. Although these findings show an overall decrease in CSM among Asian American and Pacific Islander populations, specific cancer types exhibited increased mortality rates, with further disparities by sex and age. Targeted, culturally adapted clinical and public health interventions are needed to narrow disparities in cancer mortality.

Mortality for pancreatic cancer throughout 2003-2022 in the US

Mortality for pancreatic cancer throughout 2003-2022 in the US

Association Between Physical Activity and Pancreatic Cancer Risk and Mortality: A Systematic Review and Meta-Analysis

Background: Physical activity has been associated with a lower risk of various types of cancer and reduced cancer-specific mortality. Less is known about its impact on pancreatic cancer. The aim of this systematic review and meta-analysis was to summarize evidence on the association between physical activity and pancreatic cancer risk and mortality. Methods: PubMed and Embase were searched until May 2024 for studies examining physical activity in relation to pancreatic cancer incidence and mortality. Summary risk estimates for highest vs. lowest physical activity levels were calculated using a random-effects model. The risk of publication bias was assessed with a funnel plot and Egger’s regression test. Results: A total of seven case–control and eighteen prospective cohort studies were included that investigated the association between physical activity and pancreatic cancer incidence. Our meta-analysis showed a summary estimate of 0.75 (95% CI 0.64–0.88) for case–control studies (I2 = 23%, n = 7) and a summary estimate of 0.91 (95% CI 0.86–0.97) for prospective cohort studies (I2 = 5%, n = 18). Among the six prospective cohort studies that assessed pancreatic cancer mortality, the summary estimate was 1.03 (95% CI 0.83–1.27), I2 = 50%. Conclusions: Higher levels of physical activity were associated with reduced pancreatic cancer risk. Evidence from a limited number of studies suggests that pre-diagnosis physical activity does not affect pancreatic cancer mortality.

Trend and forecast analysis of the changing disease burden of pancreatic cancer attributable to high fasting glucose in China, 1990-2021.

Pancreatic cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors. PC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection. The number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73-1.52) and 1.00% (95% CI, 0.63-1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032. It was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country's future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important.

S115 Gender and Racial Disparities in Pancreatic Cancer Mortality in Texas: A Statewide Population-Based Study

S115 Gender and Racial Disparities in Pancreatic Cancer Mortality in Texas: A Statewide Population-Based Study

S10 Trends and Disparities in Pancreatic Cancer Mortality in the United States From 1999 to 2020

S10 Trends and Disparities in Pancreatic Cancer Mortality in the United States From 1999 to 2020

Global Trend in Pancreatic Cancer Prevalence Rates Through 2040: An Illness-Death Modeling Study.

Despite remarkable progress in contemporary medical technology and enhanced survival outcomes for various cancer types, pancreatic cancer (PC) continues to stand out as a particularly deadly gastrointestinal malignancy. Given a persistent rise in both incidence and the corresponding mortality rates of PC globally, evaluations of PC burden by sex are of great importance. Here, we used the illness-death multi-state model (IDM) to forecast the prevalence of PC through the year 2040. IDM was established based on obtainable data to predict the future prevalence of PC on global, regional, and national scales from 2019 to 2040. Analyses were also performed regarding sex and 95% confidence intervals (CIs) are presented for all estimates. The projected prevalence rate for 2040 is anticipated to be 6.093 ([95% CI 5.47-6.786] per 100,000) worldwide, indicating a significant increase of 31.45% since 1990, and a 12.29% increase since 2019. The estimated average annual increase since 2020 was 0.5%. Considering sex differences, females are expected to have a steeper slope in prevalence rate than males. Intriguingly, when considering the percentage changes between the periods of 2019-2040 and 1990-2019 for both sexes, females exhibited 29% and 11% increase relative to males (2.6-fold greater increase). By 2040, it is predicted that the prevalence of PC will increase globally, with women being at higher risk of developing the disease. Considering the percentage changes, regions with lower socioeconomic status are anticipated to face a greater risk of experiencing PC compared to other geographical areas.

Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.

The increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3's role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3's critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape.

Abstract A071: County-level racial and ethnic diversity index and cancer mortality in the U.S.

Abstract Background: The United States is experiencing a demographic trend of increasing racial and ethnic diversity. While persistent racial and ethnic disparities in cancer mortality are well documented, little is known about the impact of racial and ethnic diversity on cancer outcomes in the United States. Purpose: We examined associations between the U.S. county-level racial & ethnic diversity index and age-adjusted cancer mortality rates. We also assessed whether associations differed by geographic region, persistent poverty, and rurality. Methods: We used the U.S. Census Bureau’s 2020 Racial and Ethnic Diversity Index, which estimates the chance that two people chosen at random will be from different racial and ethnic groups. The diversity index was calculated at the county-level and categorized as follows: less than 35% (lowest), 35.0 to 44.9%, 45.0 to 54.9%, 55.0 to 64.9% and 65.0% or more (highest). We described county- level sociodemographic characteristics according to the diversity index categories. We calculated mean and standard errors of the county-level age-adjusted cancer mortality rates per 100,000 from 2016-2020 (overall and by site for the top four sites for cancer mortality) across the diversity index categories. We used multivariable linear regression models to examine associations between racial and ethnic diversity and cancer mortality, overall and by cancer site. We also assessed models stratified by geographic region (U.S. Census regions), persistent poverty and rurality. Results: Counties with more racial and ethnic diversity had a younger median age, a higher proportion of college graduates, and were less likely to be rural. Cancer mortality rates per 100,000 were lower in the most vs. least diverse counties, overall (144.7 vs. 164.6), and for lung (32.5 vs. 44.8), and colorectal cancer (13.0 vs. 15.6). In adjusted models, the highest vs. lowest racial and ethnic diversity was associated with a 7.25 decrease in overall cancer mortality rates (95% CI: -10.5 to -4.0), a 6.55 decrease in lung cancer mortality (95% CI: -8.0 to -5.1) and a 1.49 increase in breast cancer mortality (95% CI: 0.7 to 2.3). The diversity index was not associated with colorectal cancer mortality or pancreatic cancer mortality in adjusted models. Inverse associations of diversity index and overall cancer mortality were strongest in the South Census region (b=-13.0, 95% CI: -17.5 to -8.4), in non-persistent poverty counties (b=-9.0, 95% CI: -12.4 to -5.5), and in rural counties (b=-8.6, 95% CI: -13.2 to -4.1). Conclusions: Greater racial and ethnic diversity was associated with lower overall cancer mortality and lung cancer mortality rates, although it was associated with significantly higher breast cancer mortality rates. Findings help elucidate whether and how social factors may differentially impact subgroups of the population to influence cancer mortality. This study addresses an urgent need to explore contextual factors that may shape racial and ethnic disparities at the population level. Citation Format: Kelly A. Hirko, Breanna Greteman, Sabrina Ford, Sarah H. Nash. County-level racial and ethnic diversity index and cancer mortality in the U.S. [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A071.

Abstract B019: Sensitivity and specificity of detecting premalignant pancreatic lesions by hyperpolarized magnetic resonance

Abstract Introduction: The high mortality rate of pancreatic cancer (PC) results from a lack of methods for early detection. The progression of PC occurs primarily via two precursor pathways, either through microscopic pancreatic intraepithelial neoplasias (PanINs) or macroscopic cystic lesions, of which intraductal papillary mucinous neoplasms (IPMNs) are the most common. The progression from either PanIns or IPMN to PC, provides an opportunity for early detection of this lethal disease. PC cells have extensively reprogrammed metabolism and we have successfully employed hyperpolarized 1-13C pyruvate metabolic imaging (HP MR) to measure non-invasively the metabolic plasticity as the disease initiates and evolves. Concurrently, the specificity of HP MR of detecting premalignant lesions will be determined by imaging pancreatitis induced mice at different timepoints and compare them to the premalignant models. Methods: HP 1-13C Pyruvate MRS was employed to study the metabolic processes in tamoxifen inducible GEM models (P48CreERT2;LSL-KrasG12D (iKC)) with pre-invasive PanIN precursor lesions, invasive PC model (P48CreERT2;LSL-KrasG12D;LSL-p53R172H (iKPC)) and control animals (P48CreERT2 (iC)). These mice were imaged at different time points, before tamoxifen induction, 10-, 20-, and 30-weeks post induction. HP MR was also employed on IPMN mouse model (p48Cre;LSL- KrasG12D;Rosa26R-LSL-rtTA-TetO-GnasR201C) that develop premalignant cystic lesions, that progresses to PC on doxycycline diet (Dox+) for 15 weeks and control mice on normal diet (Dox-). These mice were imaged after 15 weeks of (Dox±) treatment. Simultaneously, wildtype, iC and iKC mice were treated with caerulein for three weeks for the development of pancreatitis and imaged 24 hours after treatment. Results: In the PanIN model, the lactate-to-pyruvate (lac/pyr) ratio increased in the PC models compared to the control model. For the aggressive iKPC mouse model, at the 20-week post induction imaging there was a significant increase of the lac/pyr ratio (0.28±0.04) compared to the 10-week time point (0.22±0.03). At the 20-week time point, the iKPC ratio was higher than the iKC and control ratios, (0.28±0.04 compared to 0.23±0.03 and 0.22±0.02 respectively) indicating the invasive nature of the cancer. Even in the iKC model there is a slight increase of the lac/pyr ratio at 20-weeks (0.23±0.03) compared to control (0.22±0.02). Mice treated with caerulein developed pancreatitis as demonstrated by tissue histology. Surprisingly, the lac/pyr ratio remained constant in both iC and iKC mice that developed pancreatitis, around 0.15±0.03 for both groups. In the IPMN model, IPMN mice feed with doxycycline showed increase pancreatic lesions and an increased lac/pyr ratio (0.43±0.05) compared to mice on normal diet (0.24±0.05). Conclusion: HP MR can detect metabolic shift to lactate in two different models of PC premalignancy representing two different pathways of PC progression. This finding can be potentially translated to the clinic for detection of premalignant pancreatic lesions in high-risk populations. Citation Format: José S Enriquez, Rian M Howell, Olivereen Le Roux, Shivanand Pudakalakatti, Prasanta Dutta, Florencia McAllister, Pratip K Bhattacharya. Sensitivity and specificity of detecting premalignant pancreatic lesions by hyperpolarized magnetic resonance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B019.

Abstract IA-09: Spatiotemporal metabolic networks in pancreatic cancer and associated cachexia

Abstract Cachexia or body wasting is a significant contributing factor to the morbidity and mortality of pancreatic cancer. Despite an unmet need, its metabolic underpinnings remain poorly understood. Here, we characterize an inducible mouse model of pancreatic cancer cachexia that recaptures human disease progression. We present longitudinal systemic metabolic profiling analyses through pre-, early and late cachexia stages in male and female pancreas, its interstitial fluid (IF), plasma, liver, adipose and skeletal muscle. We find that each tissue has a unique metabolome and trajectory across stages, and reveal metabolic signatures with marked lipid enrichment in the pancreatic IF. Using mathematical modeling, we identify metabolites participating in cross-tissue networks and in vivo validate a lactate-hexose connection. We find systemic metabolic changes prior to weight loss, and use feature selection algorithms to identify potential predictive markers of cachexia progression. Our study provides a resource for system-wide metabolic network evolution of pancreatic cancer cachexia, highlighting the potential for prevention and therapy. Citation Format: Blanca Majem, Min-Sik Lee, Kyung Cheul Shin, Insia Naqvi, Courtney Dennis, Lucas Dailey, Sarah Jeanfavre, Mari Mino-Kenudson, Joao B Xavier, Clary B Clish, Deepti Mathur, Nada Y Kalaany. Spatiotemporal metabolic networks in pancreatic cancer and associated cachexia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr IA-09.

Abstract PR-02: Uncovering molecular differences in pancreatic ductal adenocarcinoma tissues from Black and White patients in the US

Abstract Background: Pancreatic cancer (PC) is among the leading causes of cancer-related deaths in the United States, with a 5-year survival rate of approximately 13%. Previous studies reported higher PC incidence and mortality rates among Black or African American (BAA) patients in comparison to White patients. Disadvantaged socioeconomic status (SES) and environmental exposure to chemicals are factors contributing to racial disparities in pancreatic cancer. Whether and how biological pathways play roles in disparities in pancreatic cancer is unclear. The understanding of molecular features associated racial backgrounds in pancreatic cancer will have significant impacts on both scientific inquiry on cancer biology and clinical management of pancreatic malignancy. In this study, we examined oncogene alterations and PD-L1 expression in pancreatic cancer patients of diverse racial backgrounds. Methods: We conducted our study by analyzing clinical test results of patients through a collaboration with Tempus Labs. In total, 4,249 pancreatic cancer patients’ (White: 3797 and BAA: 452) information were included in this study. DNA target panel sequencing was performed to identify genomic mutations. Genomic microsatellite instability (MSI) and tumor mutational burdens (TMB) were assessed. We also evaluated PD-L1 expression by immunohistochemistry. Results: DNA sequencing analysis revealed differential gene mutation profiles between White and BAA patients. We observed higher rates of KRAS (79.2% vs. 74.2%, q=0.14), TP53 (69.9% vs. 61.9%, q=0.014), KMT2C (6.9% vs. 2.3%, q=0.001), RNF43 (6% vs. 3.7%, q=0.14), and KMT2D (4.4% vs. 2.8%, q=0.3) mutations among BAA patients compared to White patients whereas fewer GNAS (0.2% vs 1.6%, q=0.14) mutation occur in the BAA group. Importantly, the KRAS mutant allele KRASG12R was significantly enriched in BAA compared to White patients (14.4% vs. 10.1%). Next, we compared the TMB levels and found that BAA patients showed higher average TMB levels when compared to White patients. Further, we determined the expression of PD-L1 between the two racial groups and observed BAA patients had more frequent PD-L1 overexpression than White patients (13.2% vs. 8.6%, p<0.05). Interestingly, the race associated difference in PD-L1 expression was even more remarkable in female groups (14.1% vs. 8%, p<0.05). Conclusion: We observed differences in mutation profiles of oncogenes between BAA and White patients, suggesting that such molecular-level changes may contribute to the higher incidence among BAA patients. Additionally, higher frequencies of PD-L1 upregulation in BAA patients implicate racial backgrounds influence tumor microenvironment regulation in pancreatic cancer patients. It is imperative to improve racial diversity in translational and clinical studies. Citation Format: Saurabh Mandal, Emily A Teslow, Minxuan Huang, Swathi Sridhar, Howard Crawford, Melissa C Stoppler, Albert Levin, Ling Huang. Uncovering molecular differences in pancreatic ductal adenocarcinoma tissues from Black and White patients in the US [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-02.

Effect of Sodium-Glucose Co-Transporter 2 Inhibitors Combined with Metformin on Pancreatic Cancer Cell Lines.

Pancreatic cancer (PC) is the ninth-leading cause of cancer-related deaths worldwide. Diabetic patients have an increased risk and mortality rates for PC. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and metformin (Met) are widely used anti-diabetic medications. Both Met and SGLT2 inhibitors have anticancer properties in PC, but nothing is known concerning their combined effect. So, we investigated the in vitro effect of SGLT2 inhibitors combined with Met. Canagliflozin and dapagliflozin possessed cytotoxic, antiproliferative, and pro-apoptotic properties in the tested PC cell lines. In PANC-1 cells, the antimigratory and pro-apoptotic effects were enhanced when dapagliflozin was combined with Met, and G1 cell cycle arrest was enhanced when dapagliflozin or canagliflozin was combined with Met. In AsPC-1 cells, the cytotoxic effect and the G1 cell cycle arrest were enhanced when canagliflozin and dapagliflozin, respectively, were combined with Met. Only the cytotoxic effects of SGLT2 inhibitors, but not the combination treatments, involved PI3K and JNK-dependent pathways in AsPC-1 cells. In conclusion, combination treatments increased the anticancer effects in a cell type-dependent way in the two investigated cell lines. Additionally, the cytotoxic effect of SGLT2 inhibitors was dependent on the PI3K and JNK pathways in AsPC-1 cells, but Met appears to act via a distinct mechanism.

Pancreatic cancer mortality trends in the United States: how much have we moved the needle?

Despite advances made in pancreatic cancer treatment, the extent of progress made in pancreatic cancer mortality at the population level remains unclear. Our cross-sectional study sought to measure trends in pancreatic cancer mortality in the United States in the last 2 decades. Patients with pancreatic cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were measured. We used joinpoint trend analysis to determine average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, pancreatic cancer accounted for 809,197 deaths. Overall, the AAMRs of pancreatic cancer increased from 20.74 per 100,000 individuals in 1999 to 21.60 per 100,000 individuals in 2020. The highest AAMR was recorded in non-Hispanic Black males (30.11 per 100,000 individuals), and the lowest, in non-Hispanic White females (18.51 per 100,000 individuals). Patients aged 75-84 years had the highest AAMR (6.87 per 100,000 individuals) compared to the younger patients. The highest AAMR was observed in the Northeast region (22.07 per 100,000 individuals) and rural regions (21.29 per 100,000 individuals). There was no improvement in pancreatic cancer mortality in the last two decades. These findings emphasize the importance of efforts to increase access to multidisciplinary cancer care with the realization that without it, improvements in treatment standards will not translate to lower cancer mortality at the population level.

Age-period-cohort analysis of global, regional, and national pancreatic cancer incidence, mortality, and disability-adjusted life years, 1990–2019

BackgroundPancreatic cancer is one of the deadliest cancers in the world. In recent years, the incidence and mortality rates of pancreatic cancer have shown an increasing trend year by year. This study investigates the independent effects of age, period, and cohort on the global incidence, mortality, and disability-adjusted life years (DALYs) of pancreatic cancer from 1990 to 2019, and evaluates the differences in the burden of pancreatic cancer across regions with different Sociodemographic Index (SDI) levels.MethodsEstimating the impact of age, period, and cohort on pancreatic cancer disease burden in different SDI regions using age-period-cohort modeling with data (with 95% uncertainty intervals [UI]) from the Global Burden of Disease (GBD) Study 2019 and net drift of age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) for pancreatic cancer in 120 countries.ResultsThe number of new cases of pancreatic cancer worldwide increased from 197,348 (95% UI: 188,604,203,971) in 1990 to 530,297 (486,175,573,635) in 2019, the number of deaths increased from 198,051 (189,329 to 204,763) in 1990 to 531,107 (491,948 to 566,537) in 2019, and the number of DALY increased from 4,647,207 (4,465,440 to 4,812,129) in 1990 to 11,549,016 (10,777,405 to 1,238,912) in 2019. The ASIR of the average levels in global pancreatic cancer increased from 5.22 (4.97 to 5.40) per 100,000 population to 6.57 (6.00 to 7.09) per 100,000 population, the ASMR increased from 5.34 (5.07 to 5.52) per 100,000 population to 6.62 (6.11 to 7.06) per 100,000 population, and the ASDR increased from 115.47 (110.82 to 119.60) per 100,000 population to 139.61 (130.18 to 149.14) per 100,000 population. The incidence, mortality, and DALY rates of pancreatic cancer increase with age globally and across all SDI regions, peaking in the 85–89 age group. In high and high-middle SDI regions, the growth rate for males is higher than for females before the age of 85, while females have a higher growth rate after 85. The 75–79 age group exhibits the highest DALY rate in high and high-middle SDI regions, significantly higher than the global and other SDI regions. From 1990 to 2019, the period effects of pancreatic cancer incidence, mortality, and DALY rates have increased significantly worldwide, while remaining almost unchanged in high and high-middle SDI regions. In contrast, period effects have significantly increased in middle, low-middle, and low SDI regions. Cohort effects are more pronounced in middle, low-middle, and low SDI regions.ConclusionsWith the aggravation of population aging, the incidence and mortality rates of pancreatic cancer in the world are increasing, and effective prevention and control measures can be achieved by reducing the exposure of risk factors. The APC model used in our analysis provides a novel approach to understanding the complex trends in the incidence, mortality, and disability-adjusted life years of pancreatic cancer. It can inform the development of targeted interventions to reduce the severe disease burden caused by pancreatic cancer.

Trends in pancreatic cancer mortality in the United States 1999-2020: a CDC database population-based study.

Pancreatic cancer is a significant public health concern and a leading cause of cancer-related deaths worldwide. This study aimed to investigate pancreatic cancer mortality trends and disparities in the United States (US) from 1999 to 2020. Data were obtained from the Centers for Disease Control (CDC) Wide-Ranging Online Data for Epidemiologic Research database. Mortality rates were age-adjusted and standardized to the year 2000 US population. Joinpoint regression was used to analyze temporal trends in age-adjusted mortality rates (AAMRs) by sociodemographic and geographic variables. Between 1999 and 2020, pancreatic cancer led to a total of 810,628 deaths in the US, an average mortality of nearly 39,000 deaths per year. The AAMR slightly increased from 10.6 in 1999 to 11.1 in 2020, with an associated annual percent change (APC) of 0.2. Mortality rates were highest among individuals aged 65 and older. Black individuals experienced the highest overall pancreatic cancer-related AAMR at 13.8. Despite this, Black individuals experienced a decreasing mortality trend over time (APC -0.2) while White individuals experienced an increasing trend in mortality (APC 0.4). Additionally, individuals residing in rural areas experienced steeper rates of mortality increase than those living in urban areas (APC 0.6 for rural vs -0.2 for urban). White individuals in urban and rural populations experienced an increase in mortality, while Black individuals in urban environments experienced a decrease in mortality, and Black individuals in rural environments experienced stable mortality trends. Mortality from pancreatic cancer continues to increase in the US, with racial and regional disparities identified in minorities and rural-dwelling individuals. These disparate findings highlight the importance of ongoing efforts to understand and address pancreatic cancer treatment and outcomes disparities in the US, and future studies should further investigate the underlying etiologies of these disparities and potential for novel therapies to reduce the mortality.

Pancreatic cancer - epidemiology, risk factors, nutritional and infl ammatory prognostic and predictive factors.

Pancreatic cancer remains one of the most challenging malignancies to treat, with consistently low survival rates despite advances in medical research. The identification and validation of effective prognostic biomarkers are crucial for improving diagnostic accuracy and treatment outcomes. The aim of the work is to analyze the latest data of the pancreatic cancer incidence and mortality, comparing them with global epidemiological data. The narrative review also aims to summarize current knowledge about various prognostic biomarkers in the pancreatic cancer treatment, including indicators of performance status, nutritional and inflammatory markers. The most recently available national epidemiological data on pancreatic cancer are analyzed. The literature review is focused on markers that evaluate the general condition of patients, such as performance status, body mass index, prognostic nutritional index and markers of the inflammatory response, such as Glasgow prognostic score, C-reactive protein, neutrophil to lymphocyte ratio, systemic inflammatory response index and systemic immune inflammation index. These biomarkers are analyzed for their role in predicting prognosis and response to systemic therapy for pancreatic cancer. Both the Slovak Republic and the Czech Republic are globally ranked in the leading places in terms of pancreatic cancer incidence and mortality, both in estimates and real data. Indicators of nutritional and performance status play a critical role in patient assessment and influence treatment decisions, with potential impact on treatment outcomes. Inflammatory markers have shown significant prognostic value, correlating with the patient's immune response to the tumor and inflammatory processes that may promote disease progression. However, despite their promising predictive capabilities, these biomarkers are not routinely used in clinical practice due to the need for further validation. Integration of new biomarkers into clinical practice could lead to more personalized therapeutic decisions and improved treatment outcomes. Further research is needed for a more comprehensive assessment of the validity of these biomarkers and their use in common clinical conditions.

Umbrella Review on the Relationship between Vitamin D Levels and Cancer.

Cancer is a growing public health problem and cancer is linked to vitamin D via several mechanisms. Recent umbrella reviews on the extra-skeletal effects of vitamin D did not turn their attention to cancer. Accordingly, an overview of the current state of research is needed. An umbrella review was conducted to provide an overview of systematic reviews on the association between vitamin D and incidence or mortality of breast cancer, colorectal cancer, lung cancer, pancreatic cancer, and prostate cancer. Inverse correlations were found between the vitamin D level (measured by circulating 25(OH)D) and mortality for all five types of cancer. For breast cancer, colorectal cancer, lung cancer, and pancreatic cancer, there are also hints of a lower incidence due to higher 25(OH)D levels. As most reviews include observational studies, conclusions on causality cannot be made. Methodological differences between the included reviews and different study designs in the individual studies lead to methodological problems. Despite these problems, the review shows inverse correlations between 25(OH)D levels and mortality, and mostly inverse correlations between 25(OH)D levels and incidence.

In Silico Identification of Dysregulated miRNAs Targeting KRAS Gene in Pancreatic Cancer.

Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation.

Trends and Variations in Pancreatic Cancer Mortality Among US Metro and Nonmetro Adults, 1999-2020.

Pancreatic cancer is the third leading cause of cancer deaths in the United States. Despite decreasing cancer mortality rates as a whole, pancreatic cancer death rates in the United States remain steady and demonstrate racial/ethnic disparities. Divergent cancer mortality trends have also been observed between metro and nonmetro populations. We therefore aimed to compare metro and nonmetro trends in pancreatic cancer mortality rates in the United States from 1999 to 2020 and investigate potential sex and racial/ethnic differences. We analyzed National Center for Health Statistics data for all pancreatic cancer deaths among individuals aged 25 years or older in the United States. We estimated the average annual percent change (AAPC) in age-standardized pancreatic cancer mortality rates in metro versus nonmetro areas by sex and race/ethnicity. Of the total 810,425 pancreatic cancer-related deaths identified from 1999 to 2020, 668,547 occurred in metro areas and 141,878 in nonmetro areas. Non-Hispanic Black individuals had the highest rates of pancreatic cancer mortality regardless of metropolitan status. In both metro and nonmetro areas, pancreatic cancer mortality rates among non-Hispanic White individuals increased over the study period (AAPC: metro, males, 0.32%; females, 0.27%; nonmetro, males, 0.77%; females, 0.62%). Non-Hispanic Black individuals in metro areas had a decrease in pancreatic cancer mortality (AAPC: males, -0.25%; females, -0.29%), but rates among non-Hispanic Black women in nonmetro areas increased (AAPC, 0.49%). There are variations not only in pancreatic cancer mortality by metro and nonmetro status but also by sex and race/ethnicity within these areas. Individuals who live in nonmetro areas have higher pancreatic cancer mortality rates and increasing death rates compared with their metro counterparts. These findings highlight the need for targeted cancer prevention strategies that are specific to metro or nonmetro populations.