In a recent publication in the American Journal of Gastroenterology, researchers conducted a study to evaluate the individual and joint correlations of excess weight and a polygenic risk score (PRS) with the prevalence of colorectal neoplasms, including nonadvanced and advanced adenomas.
For this study, the researchers analyzed data from the ongoing Begleitende Evaluierung innovativer Testverfahren zur Darmkrebsfrüherkennung (BliTz) study, which is evaluating diagnostic performance of noninvasive colorectal cancer (CRC) screening tests in screening colonoscopy participants in southwestern Germany.
The researchers noted that adjusted odds ratios (aORs) for excess weight derived by multiple logistic regression were transformed to genetic risk equivalents (GREs) to quantify the impact of excess weight compared with genetic predisposition.
The authors wrote, “To our knowledge, our study is the first to evaluate the individual and joint impact of both excess weight and PRS levels on the prevalence of colorectal neoplasms in a colonoscopy screening population and to derive GREs as a comparative measure of their impact which may be helpful for risk communication.”
For the current study, participants were enrolled in 20 gastroenterology practices between November 2005 and January 2019. To assess the independent correlation of BMI and PRS levels with colorectal neoplasms and advanced colorectal neoplasms, researchers employed multivariable logistic regression models. Corresponding GREs were measured as the ratios of regression coefficients for both variables in the logistic regression models in addition to odds ratios (ORs) for BMI and PRS.
The cohort included 4,784 participants: 2,224 individuals (median age, 62 years; men, 63%) who exhibited colorectal neoplasms as the most advanced finding in colonoscopy screening (867 with advanced neoplasms, including 811 with advanced precancerous lesions and 56 with CRC) and 2,560 individuals without abnormal findings at screening colonoscopy.
Compared with the participants without neoplasms, those with colorectal neoplasms were more likely to have lower levels of education, to be overweight or obese, to smoke, to have a higher PRS, to consume more alcohol, to consume more red and processed meat, and to have diabetes.
The results also revealed that study participants classified as overweight and obese (BMI 25 to <30 and ≥30 kg/m2) had an augmented risk of any colorectal neoplasm (aOR [95% CI] 1.26 [1.09-1.45] and 1.47 [1.24-1.75]). Obesity was linked with augmented risk of advanced colorectal neoplasm (aOR [95% CI] 1.46 [1.16-1.84]).
With regard to additional results, the authors also noted that “Dose-response relationships were seen for the PRS (stronger for advanced neoplasms than any neoplasms), with no interaction with BMI, suggesting multiplicative effects of both factors. Obese participants with a PRS in the highest tertile had a 2.3-fold (95% CI 1.7-3.1) and 2.9-fold (95% CI 1.9-4.3) increased risk of any colorectal neoplasm and advanced colorectal neoplasm, respectively. The aOR of obesity translated into a GRE of 38, meaning that its impact was estimated to be equivalent to the risk caused by 38 percentiles higher PRS for colorectal neoplasm.”
Based on their findings, the authors concluded that factors such as overweight, obesity, and polygenic risk are associated with an augmented risk of colorectal neoplasms in a multiplicative manner. The authors also noted that sustaining normal weight is projected to have a comparable effect as having 38 percentiles lower PRS.
Lastly, the authors wrote, “Further research should aim for refined measurements of the relevant exposure during the life course to more fully disclose the potential for prevention and for better targeting preventive efforts which may not only be beneficial for CRC prevention but also for the prevention of a broad range of other chronic diseases whose risk is increased by excess weight.”
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