TOPLINE

Obesity increased the risk for pancreatic cancer by 20% per SD increase in BMI, with glucose and A1c mediating approximately 16% and 20% of this association, respectively.

METHODOLOGY

• Researchers analysed 462,300 adults aged 40-69 years (mean age, 56.8 years) from the UK Biobank cohort recruited between 2006 and 2010; the complete-case analytic sample included 367,615 participants.
• Principal component analysis was performed on standardised residuals of height, weight, BMI, waist circumference, hip circumference, and waist-hip ratio to derive three phenotypes of body shapes.
• Cases of pancreatic cancer were identified through linked cancer registries and national health databases during a median follow-up duration of 10.9 years.
• Four-way decomposition mediation analysis assessed whether metabolic biomarkers (glucose, A1c, insulin-like growth factor 1, and others) mediated the association between individual anthropometric traits, body shapes, and the risk for pancreatic cancer.

TAKEAWAY

• Each 1-SD increase in BMI (4.69), waist-hip ratio (0.09), waist circumference (12.4 cm), and hip circumference (8.99 cm) was associated with a 20% (hazard ratio [HR], 1.20), 24% (HR, 1.24), 25% (HR, 1.25), and 16% (HR, 1.16) higher risk for pancreatic cancer, respectively.
• Glucose and A1c mediated part of the association between BMI and pancreatic cancer, accounting for 15.9% (P = .017) and 20.0% (P = .004), respectively.
• A body shape characterising overall obesity (principal component 1) showed a similar association with the risk for pancreatic cancer (HR, 1.20); glucose and A1c accounted for mediated proportions of 12.2% (P = .007) and 15.0% (P = .002), respectively.
• In sensitivity analyses without mutual biomarker adjustment, gamma-glutamyltransferase and urate also appeared to mediate part of the association. Gamma-glutamyltransferase accounted for 19.6% (P = .005) for BMI and 16.2% (P = .004) for principal component 1, and urate accounted for 21.9% (P = .017) and 23.0% (P = .014), respectively.

IN PRACTICE

"This study provides strong evidence that metabolic biomarkers, particularly glucose and HbA1c [A1c], mediate the association between obesity and pancreatic cancer risk. These results reinforce the critical role of glycemic regulation in obesity-related carcinogenesis and have public health relevance by supporting the development of personalized prevention strategies and targeted interventions to reduce pancreatic cancer risk in at-risk populations," the authors wrote.

SOURCE

The study was led by Amina Amadou, Centre Léon Bérard, Lyon, France. It was published online on July 11, 2026, in the British Journal of Cancer.

LIMITATIONS

The observational design did not allow firm causal inference, and residual confounding may have remained. Blood samples were collected in a non-fasting state, which may have affected some metabolic biomarkers. The mediation analysis was based on cross-sectional biomarker assessment, which limited the causal interpretation of mediator-outcome relationships.

DISCLOSURES

This study received support from the French National Cancer Institute and German Research Foundation. The authors declared having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.