Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield : Results from a nationwide prospective cohort
(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.
(Less)
- author
- organization
- publishing date
- 2022-10
- 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
- John Wiley & Sons 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
- 2024-06-13 18:17:48
@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 = {{John Wiley & Sons 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}},
}