Testing For Genetic Cancer Risk

In most cases, mutations occur randomly in different cells of the body, accumulating during lifetime and causing non-hereditary cancer. But in hereditary cases of the disease, multiple gene mutations boost the growth of malignant cells to promote its spread.

Cancer inheritance

Up to 10% of cancers occur through inheritance, when a mutant gene present either in a sperm cell or an egg cell is passed from parent to child. Most hereditary cancers have an autosomal dominant inheritance, which means that one mutant gene acquired from a parent is enough to increase risk. Accordingly, a person who carries such a mutation has a 50% chance of passing it on to their children.

The main types of cancer associated with genetic predisposition include breast, ovarian, prostate, pancreatic, stomach, large intestine and rectal (colorectal) cancer, and cancers of the hormone-producing system. Frequently, inherited mutations increase susceptibility to several cancer types and may be associated with various non-malignant abnormalities, such as skeletal defects, unusual skin pigmentation, or skin growths. Therefore, people who carry these mutations are considered to have inherited cancer susceptibility syndromes.

Syndromes associated with cancer risk

There are more than 200 syndromes associated with an increased risk of cancer. One of the best known − hereditary breast and ovarian cancer syndrome – results from a mutation in BRCA1 or BRCA2 genes, which normally protect against damage to genetic material during its replication process. This increases the risk for breast, ovarian, and pancreatic cancer in women, and breast, prostate, and pancreatic cancer in men.

Other inherited cancer syndromes include:

  • familial adenomatous polyposis syndrome (increased risk of colorectal cancer).
  • hereditary diffuse gastric cancer (increased risk of stomach cancer).
  • multiple endocrine neoplasia (increased risk of cancers in hormone-producing organs, such as the thyroid gland).
  • Lynch syndrome (increased risk of colorectal, uterine, and other cancers).
  • Li-Fraumeni syndrome (increased risk of bone, soft tissue, blood, breast, and brain cancers).
  • Cowden syndrome (increased risk of breast, thyroid, uterine, colorectal, kidney, and skin cancers).
  • Peutz-Jeghers syndrome (increased risk of colorectal, breast, lung, cervical, pancreatic, and skin cancers).
  • Von Hippel-Lindau syndrome (increased risk of brain, adrenal gland, pancreatic, and kidney cancers).

The indicators of inherited cancer susceptibility syndromes as follows:

  • cancer runs in many generations of the same family.
  • several first-degree relatives (parents, siblings, or children) have the same type of cancer.
  • cancer is diagnosed at a young age.
  • cancer affects paired organs (e.g. both breasts).
  • several types of cancer develop in one person.
  • cancer appears in an unusual part of the body (e.g. breast cancer in a man).
  • a person has accompanying congenital defects.

Testing for inherited cancer

This is done only if the patient’s history is consistent with the above hereditary patterns. In this case, a general practitioner will refer the patient to a genetic counselor, who will assess personal and family medical history, evaluate risk, decide on testing and interpret findings, and advise on further medical and psychological treatment.

The goal of genetic testing is to identify patients with an inherited cancer susceptibility syndrome before onset of the disease, or at the earliest stages of such.

Since the implicated gene is present in each cell of the body, a venous blood sample can be used for testing. It may take several weeks to get the results.

A genetic counselor may decide to look specifically for one or several mutated genes, if they have already been identified in the family, or for up to 100 genes at once. Called next-generation sequencing, this test determines the order in which the building blocks of a DNA molecule are arranged, to reveal if there have been changes (mutations) in a gene that could cause disease. This technique allows testing for a large number of mutated genes at the same time, as well as for different mutations within the same gene.

Beware negative test results

A negative genetic test in cases when a specific mutation is known to run in a family means that a person’s cancer risk is similar to that of the general population. However, when family history strongly supports the presence of an inherited cancer susceptibility syndrome, but the exact mutation is not known, a negative result does not necessarily mean that risk is not increased.

This is particularly true for so-called at-home genetic testing, offered for breast, ovarian, prostate, and colon cancers by some companies. Such tests cover just a few of the most prevalent mutations, and someone with a negative at-home test result may still have a mutation that increases cancer risk.

On the other hand, comprehensive testing may reveal genetic mutations of uncertain significance. In this situation, further consultations and tests may be needed to establish their clinical relevance.

Positive test result

A positive test confirms the inherited cancer susceptibility syndrome. It does not necessarily mean that a person will get cancer. Nevertheless, in most inherited cancer susceptibility syndromes, the risk is more than tenfold compared to that of the general population. For instance, the likelihood of breast cancer manifesting during lifetime in carriers of BRCA1 or BRCA2 gene mutations is about 65%.

Monitoring gene mutations

When cancer is present, information on gene mutations may guide treatment and help other family members to decide on testing. Even if cancer has not yet developed, this allows for rigorous monitoring, preventive measures, or early treatment for the best chance of survival.

Monitoring may consist of regular check-ups, scans, ultrasound examinations, and biopsies. Prevention may involve surgical removal of the tissue that may be affected (e.g. excision of the thyroid gland in RET mutation carriers; breast or ovaries in BRCA1 carriers; or the stomach in CDH1 carriers).

Also, certain medicines reduce risk of cancer. For example, aspirin may be used to prevent hereditary cancer of the large intestine and rectum, and oral contraceptives for the prevention of ovarian cancer. Although lifestyle has less influence on hereditary cancer than non-hereditary forms of the disease, abstaining from tobacco and alcohol, a high-fiber diet, losing excess weight, exercising, and avoiding ultraviolet light all contribute to prevention.

Research institutions and other professional organizations provide information on different aspects of inherited cancer susceptibility syndromes:

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