| Title: | Effects of Screenings in Reducing Colorectal Cancer Incidence and Mortality Differ by Polygenic Risk Scores |
| Journal: | Clinical and Translational Gastroenterology |
| Published: | 6 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33955373/ |
| DOI: | https://doi.org/10.14309/ctg.0000000000000344 |
Publication 7289
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Abstract
INTRODUCTION: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, it is unclear whether the reduction in CRC risk may differ by genetic susceptibility.METHODS: We evaluated this question in a cohort of 304,740 participants of European descent aged 50 years and older. Genetic susceptibility was measured using a polygenic risk score (PRS) constructed with risk variants identified in genomewide association studies. Cox models were used to estimate hazard ratios and 95% confidence intervals of CRC risk.
RESULTS: Over a median follow-up of 7.0 years, 2,261 incident CRC cases and 528 CRC deaths were identified. CRC screening was associated with a significantly reduced CRC incidence among individuals with a high (hazard ratio, 0.80; 95% confidence interval, 0.71-0.92) and intermediate PRS (0.84, 0.71-0.98) but not among those with a low PRS (1.03, 0.86-1.25; Pinteraction, 0.005). A similar but more evident difference was observed for mortality (Pinteraction, 0.046), with more than 30% reduced mortality observed in the high PRS group (0.69, 0.52-0.91). Among the younger group (age 50-60 years), CRC screenings were associated with a slightly (but nonsignificantly) elevated incidence and mortality in the low PRS group but a reduced risk in the high PRS group (Pinteraction, 0.043 [incidence]; 0.092 [mortality]). No significant interaction was observed in the older group (age > 60 years).
DISCUSSION: Individuals with a higher genetic risk benefited more substantially from CRC screenings than those with a lower risk. Our findings suggest that PRS may be used to develop personalized CRC screening to maximize its effect on CRC prevention.
6 Authors
- Jungyoon Choi
- Guochong Jia
- Wanqing Wen
- Jirong Long
- Xiao-Ou Shu
- Wei Zheng
Enabling scientific discoveries that improve human health