QAZIIMIlluminate Health Innovations
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Laboratory service

QAZIIM Oncology Department

Hereditary cancer and screening

Personal history, tumour type and family pedigree guide germline testing and risk-adapted surveillance.

01

Who should be assessed

Young age at diagnosis, multiple primary cancers, clustered related cancers, bilateral or multifocal disease, male breast cancer, ovarian cancer and selected pancreatic or prostate cancers can indicate inherited predisposition.1

Knudson two-hit model
Knudson two-hit model

For many tumour-suppressor genes, loss of both functional copies contributes to tumorigenesis. In hereditary predisposition, one pathogenic germline alteration is present from conception and a later somatic event can disable the remaining allele; real tumours can reach biallelic loss through several molecular mechanisms.2

Created with BioRender.com. Scientific interpretation and caption by QAZIIM.
02

Risk-adapted screening

Genetic testing does not replace established screening. A clinically significant result may justify earlier, more frequent or organ-specific surveillance for the patient and at-risk relatives.2

03

Mechanism, evidence and limitations

Molecular findings are evaluated through biological plausibility, analytical validity, tumour-specific clinical evidence and potential impact on management. Associations from another cancer type are not automatically transferable.3

04

Longitudinal and multidisciplinary interpretation

Cancer evolves across anatomical sites and under treatment pressure. Pathology, imaging, treatment history, specimen quality and molecular data are reviewed together, with repeat assessment considered only when it can answer a defined clinical question.4

References

  1. Chakravarty, D. & Solit, D. B. Clinical cancer genomic profiling. Nat. Rev. Genet. 22, 483–501 (2021).
  2. Thavaneswaran, S. et al. Therapeutic implications of germline genetic findings in cancer. Nat. Rev. Clin. Oncol. 16, 386–396 (2019).
  3. Ginsburg, O. et al. The role of genomics in global cancer prevention. Nat. Rev. Clin. Oncol. 18, 116–128 (2021).
  4. Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).
  5. Dagogo-Jack, I. & Shaw, A. T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15, 81–94 (2018).
  6. Ignatiadis, M., Sledge, G. W. & Jeffrey, S. S. Liquid biopsy enters the clinic. Nat. Rev. Clin. Oncol. 18, 297–312 (2021).