Non‐steroidal anti‐inflammatory drugs, polygenic risk score and colorectal cancer risk

Abstract

Summary Background The regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk. Aim To explore whether this association varies according to background polygenic risk for CRC. Methods Data were collected from a large population‐based case‐control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC‐related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1 year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the ‘genetic risk equivalent’ (GRE), a recently developed metric for effective risk communication. Results In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P = 0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE −32, 95% CI −41, −22). Conclusions The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.

Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk

“…The GRE has recently been developed as a novel approach for improving risk communication to the public. 20 , 21 , 22 For example, the large GRE for heavy drinking in our study indicates that the impact of reduced alcohol consumption could be as strong as the impact of having a substantially lower predetermined polygenic risk for CRC, in particular EOCRC, which might help improve adherence to healthy guidelines, especially for those with a high genetic predisposition to CRC. In addition, variations regarding the relationship of heavy drinking with CRC risk by cancer location, and the estimated high GRE for distal CRC in our study further underscore the importance of targeted CRC cancer prevention.…”

“…GREs were calculated as the ratio of coefficients for alcohol consumption categories and PRS percentiles from logistic regression models, providing an estimate of alcohol impact in terms of the equivalent difference in background genetic risk. Details of the derivation of GREs have been published recently, 20 , 21 , 22 and described specifically for this study in the Supplementary Text.…”

“…The aims of this study were therefore to comprehensively assess associations of alcohol consumption with the overall CRC risk, EOCRC risk, and LOCRC risk at different levels of PRS, and to quantify the impact of alcohol drinking using the recently developed metric “Genetic Risk Equivalent (GRE)”, which may help to compare risks from environmental and genetic factors and support effective communication in practice. 20 , 21 , 22 …”

Metabolic Syndrome and Risk of Gastrointestinal Cancers: An Investigation Using Large-scale Molecular Data

“…However, a similar conclusion was reached by a German study that found no heterogeneity of the association between colorectal cancer risk and non-steroidal anti-inflammatory drug use across strata of PRS. 28 …”

Red and Processed Meat Intake, Polygenic Risk Score, and Colorectal Cancer Risk

“…In this large population-based study from Germany, we aimed to assess the association of red and processed meat intake with CRC risk across various levels of a PRS that incorporates information from 140 independent genetic variants on CRC risk [ 4 ]. Furthermore, we aimed to compare the effects of red and processed meat intake with the impact of genetic predisposition using “genetic risk equivalent” (GRE) [ 11 , 12 ], a recently developed metric aimed at enhancing effective risk communication.…”