Cancer Genetics is the field concerned with the role of inherited and acquired genetic variation in cancer susceptibility, tumour development, diagnosis, prognosis and treatment. Genetics can influence cancer through germline variants inherited from parents and present in essentially every cell, as well as somatic alterations acquired during the lifetime of a tumour and generally confined to cancer cells.
This distinction is fundamental: a somatic alteration may help explain why an existing tumour behaves or responds in a particular way, whereas a pathogenic germline variant can increase a person's inherited susceptibility to developing one or more cancers and may have implications for biological relatives. Cancer Genetics therefore connects molecular biology with clinical risk assessment, prevention, screening and treatment.
Some inherited cancer predisposition syndromes arise from pathogenic variants in genes responsible for DNA repair, cell-cycle regulation or other protective mechanisms. Examples include BRCA1 and BRCA2 variants associated with increased risks of several cancers and Lynch syndrome involving DNA mismatch-repair genes. PALB2 is another important breast-cancer susceptibility gene. The presence of a pathogenic variant does not mean that cancer is inevitable; risk depends on the gene, specific variant, biological sex, age, family history and other modifying factors. Conversely, absence of a known pathogenic variant does not eliminate familial risk because genetic testing does not detect every possible susceptibility mechanism and some familial aggregation can remain unexplained.
Cancer Genetics has both clinical and family implications. A person with a suspected inherited predisposition may be referred for genetic counselling, where personal and family histories are assessed and the possible benefits, limitations and consequences of testing are explained. Testing may involve a single gene, a syndrome-specific panel or a broader multigene panel depending on the clinical question. A pathogenic germline finding can influence surveillance, preventive interventions and treatment decisions, while also creating information relevant to biological relatives. Genetic counselling is therefore important not merely for interpreting laboratory results but for explaining inheritance, uncertainty, psychological implications, reproductive considerations and appropriate communication within families.
Genetic testing results require careful interpretation because not every detected variant is disease-causing. Results may be classified into categories such as pathogenic, likely pathogenic, uncertain significance, likely benign or benign according to established interpretive frameworks. A variant of uncertain significance should generally not be treated as proof of hereditary cancer susceptibility without supporting evidence. Conversely, a pathogenic variant may be clinically important even when the family history appears limited. The distinction between inherited predisposition and tumour-specific mutation is particularly important because a tumour sequencing result can reveal a change that is present only in the cancer and does not necessarily indicate an inherited risk.
Cancer Genetics also influences treatment through the concept of synthetic vulnerability and DNA-repair dependence. Tumours arising in people with particular inherited defects may have specific biological characteristics that make them susceptible to certain treatments. For example, BRCA1 or BRCA2 alterations can affect DNA repair and may provide a rationale for particular targeted therapies in selected cancers. Genetic information can therefore have two separate clinical roles: identifying a person's inherited risk before or after cancer develops and identifying biological characteristics of an established tumour that may affect treatment. These roles can overlap but should not be assumed to be identical.
Family history is an important component of Cancer Genetics but is not itself a genetic diagnosis. Patterns that can raise suspicion include multiple relatives with related cancers, unusually young ages at diagnosis, multiple primary cancers in one individual, rare cancers, bilateral or multifocal disease in certain contexts, or combinations of cancers characteristic of a hereditary syndrome.
However, many people with hereditary predisposition have apparently unremarkable family histories because families can be small, information may be unavailable, relatives may have died young from unrelated causes, or inherited risk may manifest variably. The fact that most breast cancers occur without a known family history illustrates why population-level cancer burden and hereditary cancer risk should not be conflated.
Cancer Genetics has developed substantially with the growth of molecular sequencing. Earlier genetic assessment often focused on a small number of well-established syndromes, whereas modern testing can examine many genes simultaneously. This expansion increases the probability of detecting clinically useful variants but also increases the frequency of uncertain findings and incidental discoveries. Genetic information can change as scientific evidence evolves, meaning a previously uncertain variant may later be reclassified. Appropriate clinical systems therefore require mechanisms for interpretation, documentation, communication and, where appropriate, reassessment. Genetic information also raises issues involving privacy, discrimination, informed consent and the handling of information that can affect relatives.
The field should be distinguished from Cancer Epidemiology because genetics investigates biological and inherited mechanisms at the individual and molecular level, while epidemiology studies patterns of disease across populations and the factors associated with those patterns. Cancer Genetics should also be distinguished from genomics, although the terms overlap: genetics traditionally emphasises genes and inheritance, while genomics considers the broader genome and interactions among many genetic elements. In contemporary oncology, Cancer Genetics contributes to prevention, risk stratification, screening, diagnosis, treatment selection and family counselling. Its significance lies in recognising that cancer susceptibility and tumour biology can have both inherited and acquired components, each requiring different forms of interpretation and clinical action.
