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

Svensson, Sara LU ; Zagoras, Theofanis ; Aravidis, Christos ; Askmalm, Marie Stenmark LU ; Björck, Erik ; Borg, Åke LU ; Kuchinskaya, Ekaterina ; Nilbert, Mef LU ; Nordling, Margareta and Rohlin, Anna , et al. (2022) In Genes Chromosomes and Cancer 61(10). p.585-591
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
colorectal cancer, genetic testing, hereditary, polyposis, syndrome, variant classification
in
Genes Chromosomes and Cancer
volume
61
issue
10
pages
7 pages
publisher
Wiley-Liss Inc.
external identifiers
  • scopus:85129227163
  • pmid:35430768
ISSN
1045-2257
DOI
10.1002/gcc.23049
language
English
LU publication?
yes
id
beabf57c-8e6c-474e-8614-590af302dbda
date added to LUP
2022-08-15 15:15:20
date last changed
2025-04-19 00:12:04
@article{beabf57c-8e6c-474e-8614-590af302dbda,
  abstract     = {{<p>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.</p>}},
  author       = {{Svensson, Sara and Zagoras, Theofanis and Aravidis, Christos and Askmalm, Marie Stenmark and Björck, Erik and Borg, Åke and Kuchinskaya, Ekaterina and Nilbert, Mef and Nordling, Margareta and Rohlin, Anna and Silander, Gustav and Lagerstedt-Robinson, Kristina and Gebre-Medhin, Samuel}},
  issn         = {{1045-2257}},
  keywords     = {{colorectal cancer; genetic testing; hereditary; polyposis; syndrome; variant classification}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{585--591}},
  publisher    = {{Wiley-Liss Inc.}},
  series       = {{Genes Chromosomes and Cancer}},
  title        = {{Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield : Results from a nationwide prospective cohort}},
  url          = {{http://dx.doi.org/10.1002/gcc.23049}},
  doi          = {{10.1002/gcc.23049}},
  volume       = {{61}},
  year         = {{2022}},
}