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.
Highlights
Colorectal cancer (CRC) is a heterogeneous disease resulting from a complex interplay between environmental and genetic risk factors
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
After excluding participants with missing information of red and processed meat intake (15 cases and 14 controls), 5109 patients with CRC and 4134 controls were included in this study (Figure 1)
Summary
Colorectal cancer (CRC) is a heterogeneous disease resulting from a complex interplay between environmental and genetic risk factors. In 2015, the International Agency for Research on Cancer rated processed meat as carcinogenic to humans (Group 1) and red meat as a probable carcinogen to humans (Group 2A) [1]. It is unclear, if and to what extent this relationship with CRC risk may vary with genetic risk of CRC. No significant interactions of red and processed meat with single CRC-related risk variants were observed after adjusting for multiple comparisons in previous studies [6–8]. These studies often suffer from very limited power, especially in the light of the harsh penalties of multiple testing and weak main effects of single variants. A polygenic risk score (PRS) built based on multiple CRC-related risk alleles might enable a more powerful assessment of gene–environment interactions
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