Obesity and Diabetes Linked to Increased Pancreatic Cancer Risk: UK Biobank Study

"The allometric lean-mass index (ALI) was linked to a 7% elevated risk, showing a significant association in men (HR: 1.13). Diabetes emerged as a strong risk factor for pancreatic cancer (HR: 1.68), with the highest risk observed in women during the first six years (HR: 2.46)," the researchers reported in Cancer Medicine.

Obesity and diabetes have been linked to an increased risk of pancreatic cancer, but the specific contributions of fat mass and fat-free mass to this association remain unclear. It is also uncertain whether general obesity poses a greater risk than abdominal obesity or if these factors, along with diabetes, independently influence pancreatic cancer risk.

For this purpose, Sofia Christakoudi, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK, and colleagues used Multivariable Cox proportional hazards models to assess the prospective associations between body composition—measured by the allometric fat-mass index and allometric lean-mass index via bioelectrical impedance—waist size, and diabetes with pancreatic cancer risk in the UK Biobank cohort. AFI and ALI were uncorrelated with each other and height, while the allometric waist-to-hip index (WHI) was independent of weight and height. Heterogeneity was evaluated based on sex, age, and follow-up time using the augmentation method (p_het).

The study led to the following findings:

• Over an average follow-up of 10.4 years, 999 cases of pancreatic cancer were identified among 427,939 participants.
• AFI was linked to an increased pancreatic cancer risk independent of ALI, WHI, diabetes, and other factors (HR: 1.102 per 1 SD increase).
• The association was stronger in women under 55 at recruitment (HR: 1.457) and men after six years of follow-up (HR: 1.159).
• ALI was also associated with a higher pancreatic cancer risk (HR: 1.072), with a stronger effect observed in men (HR: 1.132).
• WHI showed a positive association with pancreatic cancer in unadjusted models, but the link disappeared after accounting for smoking and diabetes.
• Diabetes was independently associated with higher pancreatic cancer risk (HR: 1.688), with the strongest effect in women within the first six years of follow-up (HR: 2.467).

The study indicates that general obesity, as measured by AFI and ALI, along with diabetes, is independently associated with an increased risk of pancreatic cancer. The association with AFI was more pronounced in younger women, highlighting them as a key target group for public health interventions. However, in men, the risk became more evident over a longer follow-up period, suggesting a link to cancer-related cachexia.

"Additionally, diabetes showed a stronger association closer to diagnosis in women, indicating a potential role in cancer-related diabetes induction. Abdominal obesity, however, did not demonstrate an independent association with pancreatic cancer risk after accounting for general obesity, height, smoking, and diabetes," the authors concluded.

Reference:

Christakoudi, S., Tsilidis, K. K., Gunter, M. J., & Riboli, E. (2025). Prospective Associations of Body Composition and Body Shape With the Risk of Developing Pancreatic Cancer in the UK Biobank Cohort. Cancer Medicine, 14(6), e70809. https://doi.org/10.1002/cam4.70809