The Frequency of CHEK2 variant p.Ile157Thr in Men with Prostate Cancer: Towards Expanded Genetic Testing
Abstract
Prostate Cancer (PCA) is the most commonly diagnosed cancer in men in the United States; approximately 5% to 10% of PCAs are considered to be due to inherited mutations (pathogenic variants) that substantially raise the risk for the disease. In genetic testing, variants are classified on a spectrum from mutation, variant of uncertain significance (VUS) and benign. The Checkpoint Kinase 2 gene (CHEK2) variant p. Ile157Thr has had mixed classifications from various laboratories, with some laboratories classifying the variant as a VUS, while others classifying it as a mutation. The purpose of this project was to evaluate the rate of CHEK2 p. Ile157Thr in men affected with PCA. A further objective was to compare rates of the variant to men without a diagnosis of PCA. Primers for the variant were designed by Primer3Plus and obtained from Integrated DNA Technologies. To obtain the DNA samples, DNA extraction from mouthwash samples was performed, followed by quantification and a quality assessment of the DNA using the NanoDrop 2000. The samples were genotyped with the StepOnePlus Real‐Time PCR System. Finally, a 2% confirmation test was conducted to verify the genotypes that were obtained. According to the study, 1.4% of the men with PCA exhibited the CHEK2 variant p.Ile157Thr, particularly those with family histories of breast or colon cancers. The results supported the hypothesis that the rate of CHEK2 variant p.Ile157Thr would be higher among men affected by PCA. This study explores the role of CHEK2 variant p.Ile157Thr in prostate cancer risk, and may lead to expanded genetic testing for inherited PCAs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2018
- Source ID
- 10.1096/fasebj.2018.32.1_supplement.532.9
Entities
People
- Nnedi G. Agubokwu
- Veda N Giri
Organizations
- Lincoln University
- Thomas Jefferson University
- United States Department of Defense