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CHEK2 Identified as Intermediate-risk Driver of Testicular Germ Cell Tumor Susceptibility

, by DCEG Staff

Credit: Visuals Online

Testicular Germ Cell Tumors (TGCT) are highly heritable, though despite extensive efforts no highly-penetrant cancer predisposition genes have been identified. In a new analysis, Checkpoint Kinase 2 (CHEK2) germline pathogenic variants were associated with a four-to-six times elevated risk of TGCT, with average age at presentation six years earlier than carriers of the wild-type alleles. The data were reported by investigators from DCEG, Dana-Farber Cancer Institute, and the University of Pennsylvania, and published January 24, 2019, in the journal JAMA Oncology.

The authors describe the inherited variants in CHEK2, which were observed in 4% of cases in a multi-stage case-control study involving 884 male adults, as intermediate-risk drivers of TGCT susceptibility. CHEK2 is a well-established modifier of risk for several other cancers, but it has never before been implicated in the development of familial TGCT. Mechanistically, these findings complement a growing body of evidence for CHEK2 as a master regulator of chromosomal segregation, DNA damage repair and cell cycle regulation during germ cell development and maturation.

TGCT is the most common cancer diagnosed in young men. Understanding the genetic determinants of testicular cancer could help identify individuals at greatest risk who may benefit from genetic counseling and clinical care to improve early detection.


AlDubayan SH, Pyle LC, Gamulin M, et al. Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. JAMA Oncol. January 24, 2019. DOI:10.1001/jamaoncol.2018.6477 [Epub ahead of print]

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