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Background <p>Polygenic risk scores (PRS) show potential for risk-based colorectal cancer (CRC) screening, but their utility must be assessed across diverse ancestries and tumour characteristics and compared with the current standard, the faecal immunochemical test (FIT).</p> Design <p>The cohort included 112,204 individuals from the Copenhagen Hospital Biobank (8995 with adenoma and 9246 with CRC), all with linked genetic and health registry data. A subset (<i>N</i> = 20,658) also had FIT results. CRC PRSs were evaluated for their association with lifetime adenoma and CRC risk and their predictive value individually and combined with FIT.</p> Results <p>PRS stratified population-calibrated lifetime adenoma and CRC risk independently of ancestry and sex. Individuals with a high PRS reached the incidence of low-PRS individuals up to 10 years earlier, between ages 45–60. PRS stratified risk across tumour location and histologies but showed no association among individuals with deficient mismatch repair tumours (<i>N</i> = 623). Combining PRS with FIT did not meaningfully improve prediction of adenoma or CRC at first screening, negative colonoscopy outcomes among FIT-positive participants, or outcomes within 2 years after a negative FIT.</p> Conclusion <p>PRS stratifies lifetime adenoma and CRC risk and may inform risk-based screening initiation and intensity but adds limited predictive value when combined with FIT.</p>

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Combining genome-wide polygenic scores with registry data for colorectal cancer risk-based screening

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月15日

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  • Anne Krogh Nøhr,
  • Marie Giehm Overby,
  • Mads Munk Nielsen,
  • Emil-August Torp,
  • Rikke Hedegaard Jensen,
  • Laurids Østergaard Poulsen,
  • Ole Thorlacius-Ussing,
  • Simon Ladefoged Rasmussen,
  • Berit Andersen,
  • Ismail Gögenur,
  • Erik Sørensen,
  • Ole Birger Vesterager Pedersen,
  • Christian Erikstrup,
  • Nanna Brøns,
  • Michael Schwinn,
  • Christina Mikkelsen,
  • Mie Topholm Bruun,
  • Malene Møller Jørgensen,
  • Claus Anders Bertelsen,
  • Jens Georg Hillingsø,
  • Estrid Høgdall,
  • Sisse Rye Ostrowski,
  • Karina Banasik,
  • Jakob Bay,
  • Andrea Barghetti,
  • Mette Skou Bendtsen,
  • Jens Kjærgaard Boldsen,
  • Søren Brunak,
  • Alfonso Buil Demur,
  • Johan Skov Bundgaard,
  • Lea Arregui Nordahl Christoffersen,
  • Maria Didriksen,
  • Khoa Manh Dinh,
  • Joseph Dowsett,
  • Christian Erikstrup,
  • Josephine Gladov,
  • Daniel Gudbjartsson,
  • Thomas Folkmann Hansen,
  • Dorte Helenius Mikkelsen,
  • Lotte Hindhede,
  • Henrik Hjalgrim,
  • Jakob Hjorth von Stemann,
  • Bitten Aagaard Jensen,
  • Ingileif Jónsdóttir,
  • Kathrine Kaspersen,
  • Bertram Dalskov Kjerulff,
  • Lisette Kogelman,
  • Mette Kongstad,
  • Susan Mikkelsen,
  • Christina Mikkelsen,
  • Line Hjorth Sjernholm Nielsen,
  • Janna Nissen,
  • Mette Nyegaard,
  • Frederikke Byron Pedersen,
  • Ole Birger Pedersen,
  • Liam James Elgaard Quinn,
  • Þórunn Rafnar,
  • Palle Duun Rohde,
  • Klaus Rostgaard,
  • Andrew Joseph Schork,
  • Kari Stefansson,
  • Hreinn Stefánsson,
  • Jacob Træholt,
  • Unnur Þorsteinsdóttir,
  • Henrik Ullum,
  • Thomas Werge,
  • David Westergaard,
  • Michael Patrick Achiam,
  • Christian Brieghel,
  • Rasmus Froberg Brøndum,
  • Martin Bøgsted,
  • Olafur B. Davidsson,
  • Jojo Biel-Nielsen Dietz,
  • Karen Dybkær,
  • Kirsten Grønbæk,
  • Mathias Ærendahl Heldbo,
  • Hannes Helgason,
  • Jens G. Hillingsø,
  • Henrik Hjalgrim,
  • Simon Husby,
  • Estrid Høgdall,
  • Tereza Fait Kadlec,
  • Bertram Kjerulff,
  • Hildur Knutsdottir,
  • Ragnar Pétur Kristjánsson,
  • Ulrik Lassen,
  • Cecilie Velsoe Maeng,
  • Magnus K. Magnusson,
  • Pei Meng,
  • Carsten Utoft Niemann,
  • Anne Krogh Nøhr,
  • Sisse R. Ostrowski,
  • Inge Søkilde Pedersen,
  • Hans-Christian Pommergaard,
  • Liam Quinn,
  • Andreas Røder,
  • Simon N. Stacey,
  • Hein V. Stroomberg,
  • Rebecca Svanberg Teglgaard,
  • Steffen UIlltz Thorsen,
  • Unnur Thorsteinsdottir,
  • Bragi G. Walters,
  • Martin Bøgsted,
  • Rasmus Froberg Brøndum

摘要

Background

Polygenic risk scores (PRS) show potential for risk-based colorectal cancer (CRC) screening, but their utility must be assessed across diverse ancestries and tumour characteristics and compared with the current standard, the faecal immunochemical test (FIT).

Design

The cohort included 112,204 individuals from the Copenhagen Hospital Biobank (8995 with adenoma and 9246 with CRC), all with linked genetic and health registry data. A subset (N = 20,658) also had FIT results. CRC PRSs were evaluated for their association with lifetime adenoma and CRC risk and their predictive value individually and combined with FIT.

Results

PRS stratified population-calibrated lifetime adenoma and CRC risk independently of ancestry and sex. Individuals with a high PRS reached the incidence of low-PRS individuals up to 10 years earlier, between ages 45–60. PRS stratified risk across tumour location and histologies but showed no association among individuals with deficient mismatch repair tumours (N = 623). Combining PRS with FIT did not meaningfully improve prediction of adenoma or CRC at first screening, negative colonoscopy outcomes among FIT-positive participants, or outcomes within 2 years after a negative FIT.

Conclusion

PRS stratifies lifetime adenoma and CRC risk and may inform risk-based screening initiation and intensity but adds limited predictive value when combined with FIT.