Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence.

ABSTRACT:

Background and aims

Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.

Methods

To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20-80%), or high PRS (> 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively.

Results

Depending on the PRS, the CRC lifetime incidence for

SUBMITTER: Hassanin E 

PROVIDER: S-EPMC9987090 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature