Double CHEK2 Variants and Cancer Risk
Author Information
Author(s): Bychkovsky Brittany L. MD MSc, Agaoglu Nihat B. MD PhD, Horton Carolyn MS, Polfus Linda PhD, Richardson Marcy E. PhD, Young Colin PhD, Scheib Rochelle MD, Garber Judy E. MD MPH, Rana Huma Q. MD MPH
Primary Institution: Dana-Farber Cancer Institute
Hypothesis
Are CHEK2 low-risk (LR) variants p.I157T, p.S428F, and p.T476M associated with cancer phenotype when in a biallelic state similar to biallelic pathogenic and likely pathogenic variants (PVs) in CHEK2?
Conclusion
Individuals with 2 LR variants in CHEK2 had a cancer phenotype similar to those with a single LR variant and similar to wild-type controls.
Supporting Evidence
- Individuals with 2 LR variants had a cancer prevalence of 76.9%, similar to wild-type controls.
- 95.0% of individuals with 1 PV and 1 LR variant had a prior cancer diagnosis.
- Individuals with 2 LR variants had a similar cancer phenotype to those with a single LR variant.
Takeaway
This study looked at how certain gene changes might affect cancer risk. It found that having two specific low-risk gene changes doesn't seem to increase cancer risk more than having one.
Methodology
This retrospective observational cohort study examined cancer phenotype by CHEK2 genotype in individuals who underwent genetic testing.
Potential Biases
The study population is racially homogenous, predominantly White.
Limitations
The study had relatively few individuals with biallelic CHEK2 variants and was subject to bias as cases were ascertained through clinical cancer genetic testing.
Participant Demographics
92.1% were female, median age at testing was 53 years, and included various racial and ethnic backgrounds.
Digital Object Identifier (DOI)
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