In order to provide patients with accurate information and appreciate when a referral to the cancer genetic department would be helpful it is essential to understand the difference between germline and somatic genetic testing.

Two examples of common somatic gene tests are:

The genome refers to an organism's complete set of genetic information, including all of the genes. Each genome contains all of the information that organism requires to function. In humans the genome is made up of over 3 billion DNA base pairs and contains over 20,000 genes. Genes make up only approximately 1–5% of the genome. The rest of the DNA is important for regulating the genes and the genome. There is still a lot to learn about how the genome functions (Genomics England [52]).

In the oncology setting the cancer genome refers to the sequencing of the genes within a tumour sample. The catalogue of mutations within a tumour is specific to that tumour, and the range and types of mutations provide information to cancer researchers and to clinicians treating the patient (Stratton et al. [159]).

A cancer predisposition gene is a gene in which germline mutations confer highly or moderately increased risks of cancer (Rahman [126]). For the purposes of this chapter this refers to genes in which rare mutations confer high or moderate risks of cancer (> 2‐fold relative risks) and at least 5% of individuals with relevant mutations develop cancer (Rahman [126]). A mutation is defined as a permanent change in the DNA sequence (Richards et al. [138]) and this change is also called a variant. Colloquially, ‘mutation’ is often used to describe a disease‐causing (pathogenic) variant in a particular gene (e.g. the patient has a BRCA1 mutation). However, the genes of any individual will contain many variants and most variants are not harmful (Richards et al. [138]).

Variants can be pathogenic, probably pathogenic, variation of uncertain significance (VUS), likely benign or benign. Pathogenic variants, and probably pathogenic variants are disease‐causing changes in the DNA sequence. Information about these variants can be taken into account when assessing genetic risk and making healthcare decisions. Benign and probably benign variants are not harmful and would not be taken into account when assessing genetic risk. Variants of uncertain significance are changes in the DNA code that may or may not be harmful, but there is insufficient evidence to understand how the change in the DNA sequence may alter the function of the gene. The presence of a VUS should not change the management of the patient (Richards et al. [138]).

All cancer is caused by the accumulation of pathogenic mutations in the DNA within a cell. Genetic mutations may be acquired (occurring during someone's lifetime) or inherited (also called germline mutations). Most cancer occurs as a result of acquired DNA damage, for example in response to environmental factors such as smoking and radiation. These cancers are called ‘sporadic’ cancers. Only 2–3% of cancers are linked to inherited pathogenic mutations – they are a very rare cause of cancer, overall (Cancer Research UK 2016, Kluijt et al. [84]). There are specific types of cancer where a small proportion of cases are due to an inherited mutation (Table 20.9).

Most patients with cancer will not require genetic input or testing as most cancers are sporadic. However, it is important to be able to recognize patients who may benefit from a genetics referral, to know how make a referral and to be able to communicate with patients about what to expect at their genetics appointment. It is also useful to be able to know where to access reliable information about cancer genetics (Kirk [80]).

Most germline genetic testing is arranged through a clinical cancer genetics service. The patient's personal history of cancer and their family history of cancer are assessed to determine the likelihood of identifying a germline mutation. If the chance of finding a mutation in a specific cancer predisposition gene or group of genes is significant (usually if there is at least a 10% chance), genetic testing is offered (Jacobs et al. [77]). This information is important for the person undergoing testing as it may inform current or future cancer treatments, preventative options and screening recommendations.

It is also important for the wider family as testing can be carried out in blood relatives to identify who else is at risk and to advise on risk management options. Wherever possible, genetic testing is offered to the patient affected by the cancer, rather than their unaffected relative, in the first instance. If a germline mutation in a cancer predisposition gene is identified, so‐called ‘predictive’ genetic testing can then be offered to the unaffected relatives of the patient (Jacobs et al. [77]) to provide them with genetic information about their risk. It is important that genetic counselling is provided to people considering genetic testing so that a person is informed about all possible outcomes of the genetic test.