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

Abstract

High red and processed meat intake (RPMI) is an established risk factor for colorectal cancer (CRC). We aimed to assess the impact of RPMI on CRC risk according to and in comparison with genetically determined risk, which was quantified by a polygenic risk score (PRS). RPMI and potential confounders (ascertained by questionnaire) and a PRS (based on 140 CRC-related loci) were obtained from 5109 CRC cases and 4134 controls in a population-based case–control study. Associations of RPMI with CRC risk across PRS levels were assessed using logistic regression models and compared to effect estimates of PRS using “genetic risk equivalent” (GRE), a novel metric for effective risk communication. RPMI multiple times/week, 1 time/day, and >1 time/day was associated with 19% (95% CI 1% to 41%), 41% (18% to 70%), and 73% (30% to 132%) increased CRC risk, respectively, when compared to RPMI ≤ 1 time/week. Associations were independent of PRS levels (pinteraction = 0.97). The effect of RPMI > 1 time/day was equivalent to the effect of having 42 percentiles higher PRS level (GRE 42, 95% CI 20–65). RPMI increases CRC risk regardless of PRS levels. Avoiding RPMI can compensate for a substantial proportion of polygenic risk for CRC.

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 …”

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

“…Details of the lifestyle factors assessed in the DACHS study have been described in recent studies 11,[13][14][15][16] . Briefly, highly detailed information on current and prior smoking behavior, including years of initiation and cessation and amounts of smoking, was obtained from each participant and used to calculate pack-years for current smokers and former smokers (defined as people who had ever smoked and had ceased for at least 2 years).…”

“…Therefore, whether and to what extent lifestyle factors interact with genetic risk, and to what extent increased polygenic risk can be offset by a healthy lifestyle, must crucially be demonstrated. Comparisons between the effects of individual lifestyle factors and polygenic risk have recently been conducted with the genetic risk equivalent (GRE), a novel metric to enhance effective risk communication in cancer preventive efforts [11][12][13][14] .…”