---
title: "Early-onset pancreatic cancer in women of childbearing age: global burden and metabolic risk links"
id: "plos-one-19-burden-of-early-onset-pancreatic-cancer-and-its-association-with-risk-factors"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-19-burden-of-early-onset-pancreatic-cancer-and-its-association-with-risk-factors"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356644"
published_at: "2026-08-25T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Early-onset pancreatic cancer in women of childbearing age: global burden and metabolic risk links
## Provenance & Clinical Metadata
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- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356644)
- **Published At:** 2026-08-25T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The study evaluates the global burden of **early-onset pancreatic cancer (EOPC)** among **women of childbearing age (WCBA; 15–49 years)** using GBD 2023 data and a supportive retrospective case-control analysis. - From 1990 to 2023 absolute EOPC deaths and **DALYs** in WCBA more than doubled, driven primarily by **population growth and aging**, while global age-standardized rates remained broadly stable. - Age-standardized rates increased in low and middle **Sociodemographic Index (SDI)** regions, indicating shifting epidemiology by socio-demographic strata. - **High fasting blood glucose (FBG)** was identified as the largest population-attributable risk factor for EOPC in WCBA (global PAF ≈ 64%) with an inverse SDI gradient. - **High body mass index (BMI)** showed an inverted U-shaped PAF distribution across SDI categories and lost independent significance in adjusted clinical analyses, suggesting overlapping metabolic pathways with hyperglycemia. - In the retrospective case-control study high FBG remained independently associated with EOPC (adjusted OR = 4.64; 95% CI: 2.88–7.49). - The authors note potential reverse causation may partially explain strong associations with hyperglycemia and emphasize that clinical data are hypothesis-generating rather than confirmatory. - The study calls for targeted glycemic control and metabolic interventions for WCBA to reduce EOPC risk and to support progress toward related public health goals, especially in low and middle SDI regions. - Data sources include publicly available **GBD 2023** estimates and de-identified clinical supporting information supplied as S2 Data; funding sources and competing interest statements are reported in the manuscript.
## Clinical Analysis & Structured Key Points
Burden of early-onset pancreatic cancer and its association with risk factors in women of childbearing age | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Introduction Early-onset pancreatic cancer (EOPC), diagnosed before age 50, is rising globally. Women of childbearing age (WCBA, 15–49 years) constitute nearly the same population as EOPC patients but have unique metabolic vulnerabilities. The intersection of EOPC trends with WCBA-specific metabolic risks remains underexplored. This study delineates the global EOPC burden among WCBA and its links to core metabolic determinants, providing an evidence base to guide targeted interventions in this priority population and support progress toward international development goals. Methods A two-stage design was employed. First, Global Burden of Disease 2023 data were analyzed to assess EOPC mortality and disability-adjusted life years (DALYs) among WCBA (1990–2023), quantifying trends and population attributable fractions (PAFs) for high fasting blood glucose (FBG) and high body mass index (BMI). Second, a retrospective case-control study provided supportive clinical correlation for the identified risk factors. Results Globally, absolute EOPC deaths and DALYs in WCBA more than doubled from 1990 to 2023. Age-standardized rates remained stable globally, but increased in low and middle Sociodemographic Index (SDI) regions. High FBG was the largest population-attributable risk factor (global PAF = approximately 64%), with an inverse SDI gradient. High BMI PAF showed an inverted U-shaped distribution. In the supportive clinical analysis, high FBG remained independently associated with EOPC (adjusted OR=4.64; 95% CI: 2.88–7.49), while high BMI lost significance after adjustment, suggesting overlapping metabolic pathways. Conclusion Demographic factors (population growth and aging) drive most of the increase in absolute EOPC burden among WCBA. High FBG is the leading modifiable risk factor at the population level, though reverse causation may partly explain its strong association. Targeted glycemic control and metabolic interventions are urgently needed in this population. Citation: Li J, Luo J, Hu Q, Liu Z, Luo Y, Li Y, et al. (2026) Burden of early-onset pancreatic cancer and its association with risk factors in women of childbearing age. PLoS One 21(8): e0356644. https://doi.org/10.1371/journal.pone.0356644 Editor: Sara Hemati, SKUMS: Shahrekord University of Medical Science, IRAN, ISLAMIC REPUBLIC OF Received: March 16, 2026; Accepted: August 5, 2026; Published: August 25, 2026 Copyright: © 2026 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The GBD 2023 data used in this study are publicly available from the Global Burden of Disease Study database ( https://ghdx.healthdata.org/gbd-2023) . The de-identified clinical data supporting the findings of the case-control validation study are available as Supporting Information ( S2 Data ) accompanying this manuscript. All clinical data have been fully anonymized and contain no personal identifiable information. Funding: This work was supported by three research projects funded by Bishan Hospital of Chongqing Medical University—Project No. BSKJ2023017, awarded to Jing Luo, entitled “Application Study of Indocyanine Green Molecular Fluorescence Imaging Technology in Debridement of Diabetic Foot”; Project No. 2024122459, awarded to Jiaxing Li, entitled “Disease Burden and Risk Factor Analysis of Early-Onset Pancreatic Cancer in Women of Reproductive Age”; and Project No. BYKY-CX-202504, awarded to Rui Tao, entitled “Outstanding Research Innovation Team–Rui Tao.” The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. For more information about the funder, please visit: https://www.bsrmyy.com/yygk . Competing interests: The authors have declared that no competing interests exist. Introduction Pancreatic cancer is a leading cause of cancer-related mortality globally and currently ranks as the fourth most frequent cause of cancer death. Its incidence and mortality rates have continued to climb in recent years, while the five-year survival rate remains dismal at approximately 10% [ 1 ]. The majority of patients are diagnosed at an advanced, incurable stage, and even among those who undergo surgical resection, roughly 80% will eventually succumb to disease recurrence [ 2 , 3 ]. Despite advances in treatment modalities and ongoing clinical investigations, the overall prognosis for pancreatic cancer has seen little improvement. A particularly concerning trend is the rising incidence of early-onset pancreatic cancer (EOPC), defined as diagnosis before the age of 50, which is now observed in numerous regions worldwide [ 4 ]. This increase presents a significant public health challenge [ 5 ]. Clinically, EOPC in younger patients is often associated with more aggressive pathological features, such as perineural invasion and poor differentiation, compared to its later-onset counterpart [ 6 , 7 ]. Consequently, a deeper understanding of the disease burden of EOPC and its underlying determinants is of substantial clinical and public health importance. Metabolic dysregulation, particularly hyperglycemia and obesity, are well-established risk factors for pancreatic cancer. Hyperglycemia can promote tumor cell proliferation and inhibit apoptosis by activating signaling cascades such as the RAS-MAPK pathway via insulin and insulin-like growth factor-1 (IGF-1) [ 8 ]. Separately, obesity contributes to a pro-carcinogenic microenvironment; the secretion of pro-inflammatory cytokines like IL-6 and TNF-α from visceral adipose tissue activates pancreatic stellate cells, fostering fibrosis and chronic inflammation [ 9 ]. These two factors often act synergistically, exacerbating insulin resistance and inflammation, thereby amplifying the risk of pancreatic carcinogenesis [ 10 , 11 ]. The United Nations Sustainable Development Goals (SDG3) aim to reduce maternal mortality and improve non-communicable disease prevention. In this context, the health of women of childbearing age (WCBA, defined as 15–49 years) is paramount—not only for maternal outcomes but also for their own cancer risk [ 12 ]. WCBA are particularly vulnerable to metabolic disturbances due to physiological changes in the reproductive years. Conditions such as gestational diabetes mellitus and polycystic ovary syndrome increase the prevalence of hyperglycemia and insulin resistance in this age group, potentially elevating their susceptibility to EOPC. Because EOPC (diagnosed before age 50) and WCBA (aged 15–49) are essentially the same population, focusing on WCBA allows us to highlight reproductive-age metabolic risks that may be overlooked in general EOPC studies [ 13 , 14 ]. Epidemiological evidence supports this, indicating that WCBA with glycemic abnormalities or obesity face a significantly increased risk of pancreatic cancer [ 15 ]. Therefore, in the context of the global epidemics of diabetes and obesity, implementing targeted metabolic health management and EOPC risk prevention strategies for WCBA is of critical practical importance. Despite this overlap, systematic investigations into the burden of EOPC specifically framed around WCBA metabolic vulnerabilities remain scarce, particularly in resource-limited settings. This knowledge gap prevents adequate attention from being directed toward this high-risk group and may hinder progress toward relevant public health objectives. With the global burden of metabolic diseases continuing to escalate [ 16 ], a systematic evaluation of the epidemiological characteristics of EOPC in WCBA and its association with high fasting blood glucose (FBG) and high body mass index (BMI) is urgently needed to inform the development of stratified prevention and intervention strategies. To address this research gap, the present study adopted a two-stage design. In the first stage, we utilized data from the Global Burden of Disease (GBD) 2023 study to systematically assess the global burden of EOPC among WCBA from 1990 to 2023, stratifying by Sociodemographic Index (SDI). We also quantified the population-attributable risk of key metabolic factors. In the second stage, we conducted a retrospective case-control study to provide supportive clinical correlation for the primary metabolic risk factors identified in the GBD analysis, acknowledging that the clinical data are hypothesis-generating rather than confirmatory. The findings are intended to provide a robust scientific foundation for early screening and targeted interventions for EOPC in this vulnerable population. Methods Analysis of global burden of disease data Data sources and definitions. Data were obtained from the GBD 2023 study, coordinated by the Institute for Health Metrics and Evaluation. This study integrates global data sources including vital registries, surveys, hospital records, and literature, applying standardized modeling to produce comparable disease burden estimates. The study population comprised women aged 15–49 years globally. EOPC was defined as pancreatic cancer diagnosed before age 50. Pancreatic cancer was defined using ICD-10 code C25. Key metrics included deaths and disability-adjusted life years (DALYs). Age-standardized rates (ASRs) per 100,000 population with 95% uncertainty intervals (UIs) were calculated to facilitate cross-population comparisons [ 17 ]. Stratification by sociodemographic index. Countries were stratified using the Sociodemographic Index (SDI), a composite measure of per-capita income, mean education, and fertility rate. Regions were categorized as high, high-middle, middle, low-middle, and low SDI [ 18 ]. Trend and decomposition analysis. Temporal trends were assessed using estimated annual percentage change (EAPC) derived from a log-linear regression model: ln(ASR) = α + β(year), where EAPC = 100 × (e^β − 1) [ 19 ]. Joinpoint regression was applied to identify significant inflection points in the trend. The maximum number of joinpoints was set to 5. Model selection was performed using a permutation test with a significance level of α = 0.05. For each segment, the annual percentage change was calculated, and the average annual percentage change for the entire period 1990–2023 was also computed [ 20 – 22 ]. A demographic‑epidemiological decomposition method was used to partition the absolute change in EOPC burden into three components: population growth, population aging, and epidemiological changes. The decomposition formula is as follows: the total change in the number of deaths from time t 1 to t 2 equals the sum of the contribution of population growth, the contribution of changes in age structure, and the contribution of changes in age‑specific mortality rates. Using a stepwise replacement approach, each component was estimated independently, and the sum of the three components equals the net observed change in death counts [ 23 ]. Predictive modeling and risk attribution. A Bayesian Age-Period-Cohort (BAPC) model with integrated nested Laplace approximation (INLA) and second-order random walk priors for age and period projected EOPC burden through 2050. We performed out-of-sample validation by training the model on 1990–2015 data and comparing predictions to observed 2016–2023 data. The mean absolute percentage error was approximately 12%, indicating acceptable calibration [ 24 ]. Population attributable fractions for metabolic risk factors were obtained directly from the GBD Comparative Risk Assessment framework. Specifically, the PAF for each risk factor was extracted from the GBD 2023 results database and not independently recalculated. The GBD framework computes PAF using the formula: PAF = P × (RR − 1) / (1 + P × (RR − 1)), where P is the exposure prevalence in the population and RR is the relative risk for the risk‑outcome pair derived from meta‑analyses, incorporating a theoretical minimum risk exposure level. Because the GBD database does not publicly release the disaggregated values of P and RR for each specific cause and population subgroup, we provide the exact query parameters used for extraction to ensure reproducibility. Clinical validation study Study design and participants. A retrospective case-control design provided supportive clinical correlation for key metabolic risk factors. Cases were female pancreatic cancer patients aged 15–49 years diagnosed January 2010–October 2025, with histopathological confirmation. The data for this study were accessed on 3 December 2025. Controls were healthy women aged 15–49 years undergoing routine physical examinations during the same period. Exclusion criteria included other malignancies, severe organ dysfunction, or >10% missing key variables. After exclusions, 122 cases and 366 controls were included, with a 1:3 frequency matching by age (±2 years only; no matching on socioeconomic status or comorbidities). Sample size was estimated: assuming a two-sided α = 0.05, power = 0.8, a case-to-control ratio of 1:3, a control exposure prevalence of 25% for high FBG, and an expected odds ratio of 2.0, the minimum required sample size was approximately 100 cases and 300 controls. To allow for a margin and improve statistical power, we ultimately included 122 cases and 366 controls. Variable definitions and data collection. Demographic data, height, weight, and FBG were collected. BMI was calculated as weight/height 2 (kg/m 2 ). FBG was measured using glucose oxidase. Based on WHO Asian population recommendations, high BMI was defined as ≥25 kg/m 2 and hyperglycemia as FBG ≥ 6.1 mmol/L [ 25 ]. Data on smoking, alcohol consumption, pancreatitis history, and family history of pancreatic cancer were also collected. Quality control included standardized data extraction manuals, researcher training, dual independent data entry, and random verification of 20% of records. Missing data: Cases with >10% missing values on key variables were excluded. For remaining missing values (<5% per variable), listwise deletion was applied. Statistical analysis Analyses were performed using SPSS 26.0. Categorical data were compared using χ² tests. Univariate and multivariate logistic regression assessed associations with EOPC. To avoid bias from automated variable selection, multivariable models included a pre-specified set of confounders based on literature: age, high FBG, high BMI, smoking history (binary), pancreatitis history, and family history of pancreatic cancer. No stepwise selection was used. Multicollinearity was assessed using variance inflation factors (VIFs); all VIFs were <2.5, indicating no significant collinearity. The Hosmer-Lemeshow test was used for goodness-of-fit. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Statistical significance was set at P < 0.05. This study was reviewed and approved by the Ethics Committee of Bishan Hospital of Chongqing Medical University (Approval No. cqbyky11-20251130-01). The requirement for informed consent was waived due to the retrospective nature of the study. Results The findings are presented in two sections. The first section, derived from GBD data, delineates the global burden, temporal trends, and metabolic risk attribution of EOPC among WCBA from 1990 to 2023. The second section validates the association of key risk factors with EOPC through a clinical case-control study. Global disease burden and trends of EOPC among WCBA Descriptive analysis of disease burden. From 1990 to 2023, the absolute numbers of deaths and DALYs due to EOPC among WCBA increased significantly worldwide. The number of deaths rose from 104,169 in 1990–256,770 in 2023, and DALYs increased from 2,342,183–5,249,084. However, the age-standardized mortality rate (ASMR) and DALY rate remained relatively stable during this period. The ASMR increased slightly from 5.03 to 5.15 per 100,000, while the age-standardized DALY rate decreased marginally from 109.13 to 107.59 per 100,000 ( Table 1 ). Download: PNG larger image TIFF original image Table 1. The number, ASR, and EAPC for deaths and DALYs due to EOPC among WCBA in 1990 and 2023 globally. https://doi.org/10.1371/journal.pone.0356644.t001 Burden distribution varied markedly by SDI. In 2023, high SDI regions accounted for the largest share of absolute burden (73.5% of deaths, 68.1% of DALYs). However, age-standardized rates exhibited upward trajectories in middle, low-middle, and low SDI regions during the study period. In China (a high-middle SDI country), ASMR fell from 4.09 to 3.69 per 100,000 and DALY rate from 103.99 to 82.47 per 100,000, outpacing global average declines. Geographic disparities in 2023 were pronounced. Elevated burden clustered in Eastern Europe and Central Asia, whereas parts of South, Southeast, and East Asia showed lower rates ( S1 Table ). Trend analysis. Globally, ASMR for EOPC demonstrated a slight but significant increase from 1990 to 2023 (EAPC = 0.07; 95% CI: 0.04–0.10), while DALY rate showed a modest decline (EAPC = −0.16; 95% CI: −0.19 to −0.12) ( Table 1 ). Regional trends diverged. High SDI regions experienced rising mortality (EAPC = 0.27) but stable DALY rates (EAPC = −0.03). High-middle SDI regions registered substantial declines in both metrics (mortality EAPC = −0.23; DALY EAPC = −0.66). Alarmingly, middle, low-middle, and low SDI regions all exhibited significant upward trends, signaling a rapidly escalating threat. China continued its favorable trajectory with declines in both mortality (EAPC = −0.27) and DALY rates (EAPC = −1.16). Joinpoint regression analysis. Global ASMR showed a slight upward trend (AAPC = 0.06), while DALY rate declined minimally (AAPC = −0.05). China demonstrated consistent decreases (ASMR AAPC = −0.30; DALY AAPC = −0.68) ( Figs 1 , 2 ) . Download: PNG larger image TIFF original image Fig 1. Joinpoint regression analysis on the ASR of deaths due to EOPC among WCBA. (A) global, (B) high SDI, (C) high-middle SDI, (D) middle SDI, (E) low-middle SDI, (F) low SDI, (G) China. https://doi.org/10.1371/journal.pone.0356644.g001 Download: PNG larger image TIFF original image Fig 2. Joinpoint regression analysis on the ASR of DALYs due to EOPC among WCBA. (A) global, (B) high SDI, (C) high-middle SDI, (D) middle SDI, (E) low-middle SDI, (F) low SDI, (G) China. https://doi.org/10.1371/journal.pone.0356644.g002 Regional patterns were heterogeneous. In high SDI regions, ASMR increased steadily (AAPC = 0.16). High-middle SDI regions saw declines (ASMR AAPC = −0.23; DALY AAPC = −0.42). Middle, low-middle, and low SDI regions exhibited significant increases, with middle SDI showing the fastest growth (mortality AAPC = 1.56). Notably, low SDI experienced a sharp acceleration after 2012, with mortality APC reaching 6.73 during 2021–2023, becoming the region with the most rapid burden escalation. Decomposition analysis. Globally, the rise in absolute EOPC deaths and DALYs from 1990 to 2023 was driven primarily by population growth (contributing 71.77% and 74.80%, respectively) and secondarily by aging (40.60% and 38.66%) ( Fig 3 ). In China, epidemiological shifts emerged as the predominant factor, driving a substantial reduction in both deaths (421.05%) and DALYs (284.02%) that effectively counteracted the increase attributable to population aging. The observed percentages exceeding 100% reflect the fact that favorable epidemiological trends—such as improved glycemic control—more than offset the net positive change, thereby yielding a modest overall decline; consequently, these
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