Epidemiological evidence based on observational studies has revealed that type 2 diabetes (T2D) and obesity are two major risk factors for pancreatic cancer. Pancreatic cancer is rare; however, it is associated with poor prognosis and survival rates.
In a recent study under review in the European Journal of Human Genetics and currently available on the Research Square preprint server*, researchers report that abdominal obesity as determined by body mass index (BMI) adjusted for waist-to-hip ratio (WHR) (WHRadjBMI) is an important risk factor for cancer of pancreas
Study: Abdominal obesity, more than general obesity, is a causal risk factor for pancreatic cancer. Image credit: SHISANUPONG1986 / Shutterstock.com
background
Although BMI is commonly used to determine adiposity, it is an imperfect measure of metabolic health. In contrast, WHR is more strongly associated with metabolic syndrome compared to total adiposity.
Previous genome-wide association studies (GWAS) have identified a total of 22 genome-wide signals that can be used to predict pancreatic cancer.
These detected genomic loci from GWAS can be used in methods related to Mendelian randomization (MR) and polygenic scores (PGS). Shared genetic components between epidemiologically related phenotypes are determined by PGS, while MR is used to assess causality in relationships between phenotypes using genetic variants. The shared comorbidity between obesity and pancreatic cancer has not been explained until now.
About the study
Data collected from the UK Biobank (UKBB) were assessed using PGS analysis to determine the role of total and abdominal adiposity in pancreatic cancer incidence. In addition, an MR analysis was performed between two traits of adiposity and pancreatic cancer to determine their relationship.
BMI and WHR data from 457,270 individuals were analyzed. BMI data was collected from UKBB, while WHR data was calculated by dividing waist circumference by hip circumference.
For pancreatic cancer, relevant data were obtained from hospital admissions, International Classification of Diseases (ICD) codes and self-reported data. A total of 425 pancreatic cancer cases and 457,465 controls were evaluated. Only participants of European ancestry were included in this study to minimize potential confounding factors that could be attributed to ancestry.
Results of the study
Based on large-scale data analysis using a multimodal approach, abdominal obesity was determined to be a causal risk factor for pancreatic cancer, thus confirming previous epidemiological reports.
Although the specific mechanisms related to obesity-pancreatic cancer comorbidity are not well understood, some factors, such as insulin resistance, hyperinsulinemia, and inflammation, could link obesity to pancreatic cancer. Most of the factors mentioned are associated with the metabolic syndrome, which is related to abdominal obesity. This corroborates a key finding of the present study that the causative factor of pancreatic cancer is more closely related to WHRadjBMI than to BMI alone.
Previous research has indicated that T2D is a marker of the metabolic syndrome. In the current study, aPGS analysis revealed that when adjusting for T2D status, no significant association was observed between PGSBMI, PGSWHRadjBMI and pancreatic cancer risk. Therefore, the metabolic syndrome resulting from abdominal obesity appears to be a possible risk factor for pancreatic cancer.
limitations
Pancreatic cancer is rare, which explains the small sample size in the current study. In the future, these findings will need to be validated by larger studies.
Conclusions
Compared to total adiposity, the WHRadjBMI measure of abdominal adiposity could be used to determine an increased risk of pancreatic cancer. Furthermore, the association between metabolic syndrome and increased risk of pancreatic cancer appears to be driven by T2D.
Given this finding, the authors recommend regular clinical assessments of obesity in the context of pancreatic cancer risk.
*Important news
Research Square publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or be treated as established information.
Journal reference:
- Prokopenko, I., Maina, J., Pascat, V., et al. (2022). Abdominal obesity, rather than general obesity, is a causal risk factor for pancreatic cancer. Plaza de la Recerca. doi:10.21203/rs.3.rs-1980974/v1.