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 determined by body mass index (BMI) adjusted waist-to-hip ratio (WHR) (WHRadjBMI) is a significant risk factor for pancreatic cancer.
Study: Abdominal obesity, rather than overall obesity, is a causal risk factor for pancreatic cancer. Image Credit: SHISANUPONG1986 / Shutterstock.com
Although BMI is commonly used to determine adiposity, it is an imperfect measurement for metabolic health. In contrast, WHR is more strongly associated with metabolic syndrome as 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.
Such detected genomic loci from GWAS can be used in methods related to Mendelian randomization (MR) and polygenic scores (PGS). Genetic components shared between epidemiologically related phenotypes are determined by PGS, whereas MR is used to assess causality in relationships between phenotypes using genetic variants. The shared co-morbidity between obesity and pancreatic cancer has not been explained to dated.
About the study
Data collected from the United Kingdom Biobank (UKBB) was evaluated using PGS analysis to determine the role of total and abdominal adiposity in the incidence of pancreatic cancer. In addition, MR analysis was conducted between two adiposity traits and pancreatic cancer to determine their relationship.
BMI and WHR data of 457,270 individuals were analyzed. BMI data were collected from UKBB, whereas WHR data was computed by dividing waist circumference by hip circumference.
For pancreatic cancer, relevant data from hospital admissions, International Classification of Disease (ICD) codes, and self-reported data were obtained. A total of 425 pancreatic cancer cases and 457,465 controls were assessed. Only participants of European ancestry were included in this study to minimize any potential confounding factors that could be attributed to ancestry.
Based on the analysis of large-scale data using a multi-modal 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 co-morbidity are not well understood, some factors, such as insulin resistance, hyperinsulinemia, and inflammation, could potentially connect obesity to pancreatic cancer. Most of the aforementioned factors are associated with metabolic syndrome, which is linked to abdominal obesity. This corroborates a key finding of the present study that the causal factor of pancreatic cancer is more closely related to WHRadjBMI, rather than BMI alone.
Previous research has indicated that T2D is a marker for metabolic syndrome. In the current study, aPGS analysis revealed that when adjusting T2D status, no significant association between PGSBMI, PGSWHRadjBMI, and the risk of pancreatic cancer was observed. Therefore, metabolic syndrome proxied by abdominal obesity appears to be a possible risk factor for pancreatic cancer.
Pancreatic cancer is rare, which accounts for the small sample size in the current study. In the future, these findings must be validated by larger studies.
As compared to total adiposity, the abdominal adiposity measure of WHRadjBMI 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.
Considering this finding, the authors recommend regular clinical assessments of obesity in the context of pancreatic cancer risk.
Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Prokopenko, I., Maina, J., Pascat, V., et al. (2022). Abdominal obesity, rather than overall obesity, is a causal risk factor for pancreatic cancer. Research Square. doi:10.21203/rs.3.rs-1980974/v1.