Abstract 793P
Background
Recent study suggested a role of CHEK2 loss-of-function germ-line mutations in the predisposition to testicular cancer (TC) [AlDubayan et al., JAMA Oncol 2019;5:514-522]. We attempted to validate this finding relying on high population frequency of recurrent CHEK2 pathogenic variants in Slavic populations.
Methods
CHEK2 germ-line variants were genotyped by conventional methods in TC patients and healthy controls.
Results
CHEK2 pathogenic alleles (c.1100delC (p.Thr367Metfs); del5395 [del ex9-10]; IVS2+1G>A [c.444+1G>A]) were detected in 7/280 (2.5%) TC patients vs. 3/424 (0.7%) healthy men and 6/1007 (0.6%) healthy women [OR = 4.0 (95% CI 1.5–11), p = 0.009 for pooled control groups]. Somatic CHEK2 loss-of-heterozygosity (LOH) was revealed in 4 out of 6 tumors available for analysis; strikingly all these instances of LOH involved inactivation of the wild-type allele. CHEK2 c.470T>C (p.Ile157Thr) polymorphic variant was detected in 21/280 (7.5%) affected vs. 22/424 (5.2%) non-affected men [OR = 1.5 (95% CI 0.8–2.7), p = 0.3]. Somatic CHEK2 LOH was observed only in 6 out of 21 tumors obtained from CHEK2 c.470T>C (p.Ile157Thr) carriers, with C-allele lost in two cases and T-allele deleted in four tumors.
Conclusions
The results of comparison of allele frequencies in TC patients vs. population controls coupled with the data on CHEK2 LOH status in tumor tissues support the association of CHEK2 pathogenic variants with TC risk.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study has been supported by the Russian Foundation for Basic Research.
Disclosure
All authors have declared no conflicts of interest.