Effects of common genetic variants associated with colorectal cancer risk on survival outcomes after diagnosis: a large population-based cohort study.

Yazhou He, Evropi Theodoratou, Xue Li, Farhat V.N. Din, Peter Vaughan-Shaw, Victoria Svinti, Susan M. Farrington, Harry Campbell, Malcolm G. Dunlop, Maria Timofeeva

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Genome‐wide association studies have thus far identified 130 genetic variants linked to colorectal cancer (CRC) risk (r2<0.2). Given their implication in disease causation, and thus plausible biologically effects on cancer‐relevant biological pathways, we investigated whether these variants are associated with CRC prognosis and also whether they might provide predictive value for survival outcome. We conducted the analysis in a well‐characterised population‐based study of 5,675 patients after CRC diagnosis in Scotland. None of the genetic risk variants were associated with either overall survival (OS) or CRC‐specific survival. Next, we combined the variants in a polygenic risk score, but again we observed no association between survival outcome and overall genetic susceptibility to CRC risk ‐ as defined by common genetic variants (OS: hazard ratio=1.00, 95% confidence interval=0.96‐1.05). Furthermore, we found no incremental increase in the discriminative performance when adding these genetic variants to the baseline CRC‐survival predictive model of age, sex and stage at diagnosis. Given that this study is well‐powered (>0.88) to detect effects on survival for 74% of the variants, we conclude that effects of common variants associated with CRC risk which have been identified to date are unlikely to have clinically relevant effect on survival outcomes for patients diagnosed with CRC.
Original languageEnglish
JournalInternational Journal of Cancer
Early online date4 Jul 2019
DOIs
Publication statusPublished - 1 Nov 2019

Keywords / Materials (for Non-textual outputs)

  • common genetic variants
  • Colorectal cancer
  • SURVIVAL
  • cohort study

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