Cancer is a disorder of the genome, and mutations are required for all cancers to develop. The majority of cancers—known as somatic cancers—occur sporadically. However, up to 10 percent of cancers are inherited.
Hereditary Cancer Syndrome
Hereditary Cancer Syndrome is an inherited predisposition to a syndrome with a specific pattern of tumor types. Such syndromes are usually characterized by an early onset of tumor development and presentation of multiple primary tumors that share the same causative genetic mutation in an individual.
Individuals with mutations in the Hereditary Cancer Susceptibility gene have an increased risk of developing cancers associated with the Hereditary Cancer Syndrome. The risk each individual faces varies according to the gene that is mutated, with the risk of various genes classified into high, moderate and low risk genes.
Over four fold, or 50 percent increased risk of developing cancer compared to general population.
Between two to four folds, or 20 to 50 percent increased risk of developing cancer compared to general population.
Generally up to 20 percent increased risk of developing cancer compared to general population.
Most mutations in cancer susceptibility genes are inherited in an autosomal dominant manner, meaning there is a 50 percent probability of children inheriting the mutation from an affected parent. There is also a possibility of biallelic mutations of cancer susceptibility genes occurring, though this is very rare and associated with extremely rare autosomal recessive syndromes.
Who should undergo genetic testing for Hereditary Cancer Syndromes?
There are some features in a person’s personal and family medical history that suggest a hereditary cancer syndrome. They include:
- Cancer diagnosed at a young age
- Multiple cancer types in the affected individual
- Cancer in both organs in paired organs, eg. Bilateral breast cancer
- Same cancer type in multiple blood relatives
- Unusual cancers, eg. Male breast cancer
- Presence of birth defects such as benign skin growths or skeletal abnormalities known to be associated with inherited cancer syndromes
- Being a member of an ethnic group known to have increased risk for hereditary cancer syndrome, eg. BRCA mutation in Hereditary Breast and Ovarian cancer in Ashkenazi Jewish.
Individuals who have similar personal and family medical histories can consider undergoing genetic testing for Hereditary Cancer Syndromes.
Somatic cancers are caused by mutations in a person’s non-reproductive cells. Such mutations occur in two types of genes: proto-oncogenes and tumor suppressor genes.
Proto-oncogenes are involved in normal cell function. Mutations of proto-oncogenes result in oncogenic proteins that are more active than the original protein, hence causing cells to grow and survive beyond their normal ability.
Tumor suppressor genes play the role of blocking or suppressing the development of cancer, by controlling normal cell growth and death. Mutations of these genes remove their protective effect on normal cell functions, and allow the cells to turn cancerous.
Somatic cancers, unlike hereditary cancers, are not inherited but are caused by mutations accumulated over decades in a person’s cells and tissues. There are numerous factors that cause somatic cancers, most of which are environmental, such as prolonged exposure to carcinogens like UV rays and chemicals in tobacco smoke.
Finding out about gene mutations that have caused cancers can provide guidance to cancer therapy and more personalized medicine. In other words, the availability and predicted effectiveness of some therapies can be informed by the mutation profile of the patient’s cancer. To obtain these mutation profiles of the cancer, clinical molecular genomic tumor testing is available.
There are currently two types of genomic tumor testing: one uses formalin-fixed paraffin-embedded tissue specimens extracted from the patient during a tissue biopsy, another uses blood specimen which is a non-invasive liquid biopsy.