The power of a healthy lifestyle for cancer prevention:the example of colorectal cancer

Objective:We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer(CRC)risk,to support effective risk communication for cancer prevention.Methods:A healthy lifestyle score(HLS)was derived from 5 lifestyle factors:smoking,alcohol consumption,diet,physical activity,and body adiposity.The association of lifestyle and polygenic risk score(PRS)(based on 140 CRC-associated risk loci)with CRC risk was assessed with multiple logistic regression and compared through the genetic risk equivalent(GRE),a novel approach providing an estimate of the effects of adherence to a healthy lifestyle in terms of percentile differences in PRS.Results:A higher HLS was associated with lower CRC risk(4,844 cases,3,964 controls).Those adhering to all 5 healthy lifestyle factors had a 62%(95%CI 54%-68%)lower CRC risk than those adhering to≤2 healthy lifestyle factors.The estimated effect of adherence to all 5 compared with≤2 healthy lifestyle factors was as strong as the effect of having a 79 percentile(GRE 79,95%CI 61-97)lower PRS.The association between a healthy lifestyle and CRC risk was independent of PRS level but was particularly pronounced among those with a family history of CRC in≥1 first-degree relative(P-interaction=0.0013).Conclusions:A healthy lifestyle was strongly inversely associated with CRC risk.The large GRE indicated that CRC risk determined by polygenic risk may be offset to a substantial extent by adherence to a healthy lifestyle.

A single measurement of fecal hemoglobin concentration outperforms polygenic risk score in colorectal cancer risk assessment

Dear Editors,Large-scale genome-wide association studies have identified an increasing number of single nucleotide polymorphisms(SNPs)that are associated with colorectal cancer(CRC)risk[1].Polygenic risk scores(PRS)based on all established SNPs enable clinically relevant risk assessment that may help to develop novel risk-adapted prevention and screening strategies.

Beyond familial risk: deriving risk-adapted starting ages of screening among people with a family history of colorectal cancer

Dear Editor,Colorectal cancer(CRC)is the third most common cancer globally[1],even though a large proportion of those cancers would be preventable by screening.Among those with a family history(FH)of CRC,it is commonly recommended to start screening at younger ages,e.g.,at age 40 or 10 years younger than the age at diagnosis of the youngest affected first-degree relative[2–5].Even within the group of those with a FH,risk of CRC is not homogeneous and depends on factors such as the number of affected relatives and the age at which the relatives were diagnosed with CRC[6,7],lifestyles,and genetic background profiles.However,these metrics except genetic factors may change over lifetime,which limits their use for defining starting ages of screening.The aim of this study was to evaluate whether a polygenic risk score(PRS),which combines information from CRC-related risk variants[8]and genetically determined sex(2 constant and established CRC risk factors),could effectively contribute to enhanced risk stratification.We also aimed to determine if it could assist in defining risk-adapted starting ages for CRC screening,even in individuals with a FH of CRC.The assessment was performed using the wellestablished metric of risk advancement periods(RAPs)[9],which measures the impact of an exposure on the relation of age to disease.