Physical Activity, Sedentary Behavior, and Pancreatic Cancer Risk: A Mendelian Randomization Study

Author:

Gentiluomo Manuel1ORCID,Dixon-Suen Suzanne C2,Farinella Riccardo1,Peduzzi Giulia1,Canzian Federico3ORCID,Milne Roger L245,Lynch Brigid M246,Campa Daniele1ORCID

Affiliation:

1. Unit of Genetics, Department of Biology, University of Pisa , Pisa , Italy 56126

2. Cancer Epidemiology Division, Cancer Council Victoria , Melbourne, Victoria 3004 , Australia

3. Genomic Epidemiology Group, German Cancer Research Center (DKFZ) , Heidelberg , Germany 69120

4. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne , Melbourne, Victoria 3010 , Australia

5. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University , Clayton, Victoria , Australia 3168

6. Physical Activity Laboratory, Baker Heart and Diabetes Institute , Melbourne, Victoria , Australia 3004

Abstract

Abstract Pancreatic cancer is currently the seventh leading cause of cancer death worldwide. Understanding whether modifiable factors increase or decrease the risk of this disease is central to facilitating primary prevention. Several epidemiological studies have described the benefits of physical activity, and the risks associated with sedentary behavior, in relation to cancer. This study aimed to assess evidence of causal effects of physical activity and sedentary behavior on pancreatic cancer risk. We conducted a two-sample Mendelian randomization study using publicly available data for genetic variants associated with physical activity and sedentary behavior traits and genetic data from the Pancreatic Cancer Cohort Consortium (PanScan), the Pancreatic Cancer Case-Control Consortium (PanC4), and the FinnGen study for a total of 10 018 pancreatic cancer cases and 266 638 controls. We also investigated the role of body mass index (BMI) as a possible mediator between physical activity and sedentary traits and risk of developing pancreatic cancer. We found evidence of a causal association between genetically determined hours spent watching television (hours per day) and increased risk of pancreatic cancer for each hour increment (PanScan-PanC4 odds ratio = 1.52, 95% confidence interval 1.17-1.98, P = .002). Additionally, mediation analysis showed that genetically determined television-watching time was strongly associated with BMI, and the estimated proportion of the effect of television-watching time on pancreatic cancer risk mediated by BMI was 54%. This study reports the first Mendelian randomization-based evidence of a causal association between a measure of sedentary behavior (television-watching time) and risk of pancreatic cancer and that this is strongly mediated by BMI. Summary: Pancreatic cancer is a deadly disease that is predicted to become the second leading cause of cancer-related deaths by 2030. Physical activity and sedentary behaviors have been linked to cancer risk and survival. However, there is limited research on their correlation with pancreatic cancer. To investigate this, we used a Mendelian randomization approach to examine the genetic predisposition to physical activity and sedentariness and their relation to pancreatic cancer risk, while excluding external confounders. Our findings revealed a causal link between the time spent watching television and an increased risk of pancreatic cancer. Additionally, we determined that over half of the effect of watching television on pancreatic risk is mediated by the individual's BMI.

Funder

Fondazione ARPA

Fondazione Tizzi

Victorian Cancer Agency

Publisher

The Endocrine Society

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