Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield: Results from a nationwide prospective cohort

Sara Svensson, Theofanis Zagoras, Christos Aravidis, Marie Stenmark Askmalm, Erik Björck, Åke Borg, Ekaterina Kuchinskaya, Mef Nilbert, Margareta Nordling, Anna Rohlin, Gustav Silander, Kristina Lagerstedt-Robinson, Samuel Gebre-Medhin

Research output: Contribution to journalArticlepeer-review

Abstract

Approximately 5% of patients with colorectal cancer (CRC) have a Mendelian predisposition for the disease. Identification of the disease-causing genetic variant enables carrier testing and tailored cancer prevention within affected families. To determine the panorama and genetic variation of Mendelian CRC syndromes among referrals at the cancer genetics clinics in Sweden, 850 patients clinically selected for CRC genetic investigation were included in a prospective study that tested for all major hereditary polyposis and nonpolyposis CRC conditions. Genetically defined syndromes were diagnosed in 11% of the patients. Lynch syndrome was predominant (n = 73) followed by familial adenomatous polyposis (n = 12) and MUTYH-associated polyposis (n = 8); the latter of which two patients presented with CRC before polyposis was evident. One patient with a history of adolescent-onset CRC and polyposis had biallelic disease-causing variants diagnostic for constitutional mismatch repair deficiency syndrome. Post-study review of detected variants of unknown clinical significance (n = 129) resulted in the reclassification of variants as likely benign (n = 59) or as diagnostic for Lynch syndrome (n = 2). Our results reveal the panorama of Mendelian CRC syndromes at the cancer genetics clinics in Sweden and show that unified testing for polyposis and nonpolyposis CRC conditions as well as regular reexamination of sequence data improve the diagnostic yield.

Original languageEnglish
Pages (from-to)585-591
Number of pages7
JournalGenes Chromosomes and Cancer
Volume61
Issue number10
DOIs
Publication statusPublished - 2022 Oct

Subject classification (UKÄ)

  • Cancer and Oncology
  • Medical Genetics

Free keywords

  • colorectal cancer
  • genetic testing
  • hereditary
  • polyposis
  • syndrome
  • variant classification

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