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Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer - PubMed

3 hours ago
  • #risk stratification
  • #colorectal cancer
  • #polygenic risk score
  • A high polygenic risk score (PRS) significantly increases colorectal cancer (CRC) risk across clinical risk groups compared to population controls.
  • High PRS doubles CRC risk in early-onset sporadic and familial CRC, with cumulative incidences of 24% before age 50 and 13% before age 75.
  • PRS is higher in early-onset sporadic CRC than late-onset sporadic CRC.
  • In Lynch syndrome, PRS in non-carriers falls between Lynch syndrome CRC patients and population controls.
  • Non-Lynch syndrome individuals with MSI/dMMR tumors have lower PRS than those with pMMR/MSS tumors, showing no difference from Lynch syndrome CRC cases.
  • PRS most strongly affects CRC risk in unexplained early-onset and familial CRC, while its effect in Lynch syndrome depends on gene penetrance and study design.