Excess Weight, Polygenic Risk Score, and Findings of Colorectal Neoplasms at Screening Colonoscopy

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Excess weight is a known risk factor for colorectal cancer (CRC).
• Limited data exists on how body mass index (BMI) interacts with polygenic risk scores (PRSs) in colorectal carcinogenesis.
• Understanding these interactions is crucial for risk stratification and prevention strategies.

Purpose of the Study:

• To assess the individual and combined associations of BMI and PRSs with colorectal neoplasms.
• To quantify the impact of excess weight in terms of genetic risk equivalents (GREs).

Main Methods:

• Analysis of data from 4,784 participants undergoing screening colonoscopy.
• Utilized multiple logistic regression to calculate adjusted odds ratios (aORs) for BMI.
• Converted aORs to GREs to compare the impact of excess weight with PRS.

Main Results:

• Overweight and obesity were linked to a higher risk of colorectal neoplasms.
• Obesity significantly increased the risk of advanced colorectal neoplasms.
• A multiplicative effect was observed between BMI and PRS, with obese individuals in the highest PRS tertile showing a 2.3- to 2.9-fold increased risk.
• Obesity's impact was equivalent to a 38-percentile increase in PRS.

Conclusions:

• Excess weight and polygenic risk act multiplicatively to increase colorectal neoplasm risk.
• Maintaining a normal weight offers a substantial risk reduction, equivalent to a 38-percentile decrease in PRS.