Åke Borg
Principal investigator
A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients
Author
Summary, in English
The risk of breast cancer associated with CHEK2:c.1100delC is 2-threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify CHEK2:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in CHEK2:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline CHEK2:c.1100delC, 28 familial breast cancer cases and 70 controls. Candidate alleles were selected for validation in larger cohorts. One recessive synonymous variant, rs16897117, was suggested, but no overrepresentation of homozygous CHEK2:c.1100delC carriers was found in the following validation. Furthermore, 11 non-synonymous candidate alleles were suggested for further testing, but no significant difference in allele frequency could be detected in the validation in CHEK2:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a CHEK2:c.1100delC-specific genetic modifier. Further studies of CHEK2:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.
Department/s
- LUCC: Lund University Cancer Centre
- Familial Breast Cancer
Publishing year
2021-07-20
Language
English
Pages
1-9
Publication/Series
Scientific Reports
Volume
11
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Cancer and Oncology
Keywords
- Breast Neoplasms/genetics
- Case-Control Studies
- Checkpoint Kinase 2/genetics
- Female
- Genetic Predisposition to Disease
- Germ-Line Mutation
- Humans
- Multifactorial Inheritance
- Sequence Deletion
- Exome Sequencing/methods
Status
Published
Research group
- Familial Breast Cancer
ISBN/ISSN/Other
- ISSN: 2045-2322