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Rates of Actionable Genetic Findings in Individuals with Colorectal Cancer or Polyps Ascertained from a Community Medical Setting
- Source :
- The American Journal of Human Genetics. 105:526-533
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- As clinical testing for Mendelian causes of colorectal cancer (CRC) is largely driven by recognition of family history and early age of onset, the rates of such findings among individuals with prevalent CRC not recognized to have these features is largely unknown. We evaluated actionable genomic findings in community-based participants ascertained by three phenotypes: (1) CRC, (2) one or more adenomatous colon polyps, and (3) control participants over age 59 years without CRC or colon polyps. These participants underwent sequencing for a panel of genes that included colorectal cancer/polyp (CRC/P)-associated and actionable incidental findings genes. Those with CRC had a 3.8% rate of positive results (pathogenic or likely pathogenic) for a CRC-associated gene variant, despite generally being older at CRC onset (mean 72 years). Those ascertained for polyps had a 0.8% positive rate and those with no CRC/P had a positive rate of 0.2%. Though incidental finding rates unrelated to colon cancer were similar for all groups, our positive rate for cardiovascular findings exceeds disease prevalence, suggesting that variant interpretation challenges or low penetrance in these genes. The rate of HFE c.845G>A (p.Cys282Tyr) homozygotes in the CRC group reinforces a previously reported, but relatively unexplored, association between hemochromatosis and CRC. These results in a general clinical population suggest that current testing strategies could be improved in order to better detect Mendelian CRC-associated conditions. These data also underscore the need for additional functional and familial evidence to clarify the pathogenicity and penetrance of variants deemed pathogenic or likely pathogenic, particularly among the actionable genes associated with cardiovascular disease.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
medicine.medical_specialty
Colorectal cancer
Population
Colonic Polyps
Disease
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
Genetics
medicine
Humans
Family history
education
neoplasms
Genetics (clinical)
Aged
Genetic testing
Aged, 80 and over
education.field_of_study
medicine.diagnostic_test
business.industry
Middle Aged
medicine.disease
Penetrance
digestive system diseases
Colon polyps
030104 developmental biology
030220 oncology & carcinogenesis
Female
Age of onset
Colorectal Neoplasms
business
Subjects
Details
- ISSN :
- 00029297
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- The American Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....6479ff74e337d14cf05e1841ec942771