CHEK2-associated tumour predisposition: a challenge in diagnostics and surveillance

Abstract CHEK2 is a moderate-penetrance cancer predisposition gene primarily associated with variable risks for breast cancer. The lifetime risk for developing breast cancer in females with heterozygous germline pathogenic variants in CHEK2 ranges from 15 % to 55 %, influenced by variant type (protein-truncating or missense variants), family history, age, reproductive history, polygenic risk score, environmental modifiers and breast density. For females with CHEK2 germline pathogenic variants, breast cancer surveillance is recommended. The age at onset of breast cancer surveillance, and the frequency and type of imaging, can be adapted based on personalised risk assessment. Males have an increased risk for prostate cancer, but it is yet unclear if this increased risk warrants surveillance for prostate cancer.