Genetic testing is one of the significant advancements in modern medicine. Genetic testing offers a powerful tool to discover the inherited genes that may increase an individual's risk of developing cancer.

Are you suffering from cancer or know someone going through this painful journey?

Curious about genetic testing and want to know if this could help you or your dear one in any way?

Wondering how it is done? Who all should take the test? What are the underlying factors?

Well, Karetrip is here to explain it for you.

Join us as we explore the factors related to genetic testing for cancer, empowering you to take control of your health and well-being.

What is Genetic Testing?

Genetic testing looks for specific inherited changes (variants) in a person’s genes. Genetic variants can have harmful, beneficial, neutral (no effect), or unknown or uncertain effects on the risk of developing diseases.

Harmful variants in some genes are known to be associated with an increased risk of developing cancer. These inherited variants are thought to contribute to about 5 to 10% of all cancers.

These run in families and go through generations . For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members.

Uses of Genetic Testing

• Testing whether someone carries a harmful variant in one of these genes can confirm whether a condition is, indeed, the result of an inherited syndrome.

• Genetic testing is also done to determine whether family members who have not (yet) developed a cancer have inherited the same variant as a family member who is known to carry a harmful (cancer susceptibility predisposing) variant.

• A different type of genetic testing, called tumor DNA sequencing, is sometimes done to determine if cancer cells of people who have already gotten a cancer diagnosis have genetic changes that can be used to guide treatment.

Does Someone Who Inherits a Cancer Susceptibility Variant Always Get Cancer?

No. Even if a cancer susceptibility variant is present in a family, it does not necessarily mean that everyone who inherits the variant will develop cancer.

Several factors influence whether a given person with the variant will actually develop cancer.

• One is the penetrance of the variant. When not all people who carry a variant go on to develop the disease associated with that variant, it is said to have incomplete or reduced penetrance.

• Another is their expressivity.People who inherit the variant may vary in the extent to which they show signs and symptoms of the syndrome, including the development of associated cancers.

• Lifestyle factors and environmental risks can also influence disease expression.

What Are the Available Genetic Tests for Cancer Risk Assessment?

For most of these syndromes, genetic tests for harmful variants are available.

Tests are also available for several inherited genetic variants that are not associated with named syndromes but have been found to increase cancer risk.

Examples

PALB2 (associated with increased risks of breast and pancreatic cancers)

CHEK2 (breast and colorectal cancers)

BRIP1 (ovarian cancer)

RAD51C and RAD51D (ovarian cancer)

Who Should Consider Genetic Testing for Cancer risk?

• Who have a positive family history

• Cancer which was diagnosed at an unusually young age

-Several different types of cancer occurred in the same person

• Cancer in both organs in a set of paired organs, such as both kidneys or both breasts

• Several first-degree relatives (the parents, siblings, or children of an individual) have the same type of cancer (for example, a mother, daughter, and sisters with breast cancer); family members with breast or ovarian cancer; family members with colon cancer and endometrial cancer

• Unusual cases of a specific cancer type (for example, breast cancer in a man)

• The presence of birth defects which are associated with inherited cancer syndromes, such as certain noncancerous (benign) skin growths and skeletal abnormalities associated with neurofibromatosis type 1.

• Being a member of a racial or ethnic group that is known to have an increased risk of having a certain inherited cancer susceptibility syndrome.

Genetic Counselling

What is genetic counselling ?

• It is recommended before genetic testing or after a test if it is positive

• This counselling should be performed by a trained genetic counsellor or other health care professional who is experienced in cancer genetics.

• A hereditary cancer risk assessment based on an individual’s personal and family medical history

• Discussion of - The appropriateness of genetic testing and potential harms and benefits of testing, the medical implications of positive, negative, and uncertain test results, the possibility that a test result might not be informative (that is, it might find a variant whose effect on cancer risk is not known), the psychological risks and benefits of genetic test results, the risk of passing a variant to children, the impact of testing for the family, The best test to perform

• Explanation of the specific tests that might be used and the technical accuracy of the tests and their interpretation

• Discussing various preventive care and screening strategies with the patient and their family

• Referring the patient to support groups and other information resources

• Providing emotional support to the person receiving the results

Who is a genetic counsellor and is there any need for them ?

• Genetic counsellor is a health professional who has special training in medical genetics and counselling.

• They help patients and families who have, or who may be at risk of, a genetic condition.

• They help patients understand their options for genetic testing, including its risks and benefits.

• After genetic testing is done, genetic counsellors help patients understand their genetic test results, including how the results can affect other family members, and provide counselling and support.

How is Genetic Testing Done?

• Genetic tests are usually requested by a person’s genetic counsellor, doctor, or other health care provider who has reviewed the individual’s personal and family history.

• The genetic test options from which a health professional may select include those that look at a single gene and those that look for harmful variants in multiple genes at the same time.

• Testing is done on a small sample of bodily fluid or tissue—usually blood, but sometimes saliva, cells from inside the cheek, or skin cells.

• The sample is then sent to a laboratory that specialises in genetic testing.

Genetic Testing and Insurance Policies

• Health insurance typically covers genetic counseling and many genetic tests, if they are considered medically necessary.

• A person considering genetic testing should discuss costs and health insurance coverage with their doctor and insurance company before being tested.

• The laboratory returns the test results to the doctor or genetic counsellor who requested the test. It usually takes several weeks or longer to get the test results.

What Do the Results of Genetic Testing Mean?

Genetic testing can give several possible results: positive, negative, true negative, uninformative negative, variant of uncertain significance, or benign (harmless) variant.

Positive result : A positive test result means that the laboratory found a genetic variant that is associated with an inherited cancer susceptibility syndrome. A positive result may:

• For a person who has cancer, confirm that the cancer was likely due to an inherited genetic variant and help guide treatment choicesIndicate an increased risk of developing certain cancer(s) in the future and guide future management to lower that risk

• Provide important information that can help other family members make decisions about their own health care, such as whether to have genetic testing to see if they have also inherited the variant.

• Indicate that they have an increased risk of developing cancer in the future may be able to take steps to lower their risk of developing cancer or to find cancer earlier, including: Being checked at a younger age or more often for signs of cancer

• Help in reducing their cancer risk by taking medications or having surgery to remove “at-risk” tissue.

• Help in facilitating change in personal behaviours (like quitting smoking, getting more exercise, and eating a healthier diet) to reduce the risk of certain cancers.

• Facilitate getting help to guide decisions about fertility and pregnancy.

Negative result : A negative test result means that the laboratory did not find the specific variant that the test was designed to detect.

• This result is most useful when a specific disease-causing variant is known to be present in a family.

• In such a case, a negative result can show that the tested family member has not inherited the variant that is present in their family and that this person therefore does not have the inherited cancer susceptibility syndrome tested for.

• Such a test result is called a true negative. A true negative result does not mean that there is no cancer risk, but rather that the risk is probably the same as the cancer risk in the general population.

• When a person has a strong family history of cancer but the family has not been found to have a known variant associated with a hereditary cancer syndrome, a negative test result is classified as an uninformative negative (that is, it typically does not provide useful information).

In the case of a negative test result, it is important that the person’s doctors and genetic counsellors ensure that that person is receiving appropriate cancer screening based on that person’s personal and family history and any other risk factors they may have.

Even when the genetic testing is negative, some individuals may still benefit from increased cancer surveillance.

Variant of uncertain significance : If genetic testing shows a change that has not been previously associated with cancer, the person’s test result may report a variant of uncertain significance, or VUS.

This result may be interpreted as uncertain, which is to say that the information does not help to clarify their risk and is typically not considered in making health care decisions.

Therefore, it is important for the person who is tested to keep in touch with the provider who performed the genetic testing to ensure that they receive updates if any new information on the variant is learned.

Benign variant : If the test reveals a genetic change that is common in the general population among people without cancer, the change is called a benign variant.

Everyone has commonly occurring benign variants that are not associated with any increased risk of disease.

While unfortunately no testing can be 100% error free, most genetic testing is quite accurate.

However, it is very important to have the genetic testing ordered by a provider knowledgeable in cancer genetics who can choose a reputable testing lab to ensure the most accurate test results possible.

Benefits of Genetic Testing for Inherited Cancer Susceptibility Syndromes?

• An informative negative test can provide the person with peace of mind that a harmful gene variant was not inherited.

• A positive test result provides the person an opportunity to understand and, in some cases, manage their cancer risks.

• For people who are already diagnosed with cancer, results of genetic testing may help them make decisions about their treatment and understand their risk for other cancers.

• Genetic testing provides an opportunity for family members to learn about their own cancer risks.

Risks of Genetic Testing

• Psychological stress of learning that one has a genetic variant that increases cancer risk and having to decide whether to share those findings with blood relatives.

• An uninformative test result, such as a report of a variant of uncertain significance (VUS), increases uncertainty and may increase stress until results are clarified.

• Survivor guilt upon learning that one doesn’t have a harmful variant that is present on other members of the family.

• Cost of testing itself and additional follow-up testing, if not covered by insurance.

• Privacy and discrimination issues.

• Incorrect or misleading information provided by DTC or clinical genetic testing.

Future of Genetic Testing

• The goal of another avenue of research is to provide doctors and patients with better information about the cancer risks associated with specific genetic variants, particularly variants of uncertain significance.

• For example, one research approach, called saturation genome editing, used CRISPR-Cas9 gene editing to create 4000 different genetic variants throughout a region of the BRCA1 gene that is important for its function as a tumour suppressor.

The gene editing was done in special cells that cannot survive without a functioning BRCA1 protein. For variants where clinical data were available, the gene editing results agreed with clinical findings more than 96% of the time, suggesting that this approach can be used to classify the cancer risks associated with variants of uncertain significance in other genes.

• Collaborative efforts that bring together genomic and clinical data, such as the BRCA Exchange .

• NCI runs an active program of Genome Wide Association Studies (GWAS) through its Cancer Genomics Research Laboratory .This technique compares the genomes from many different people to find genetic markers associated with particular observable characteristics or risk of disease.

• The goal is to understand how genes contribute to the disease and to use that understanding to help develop better prevention and treatment strategies.

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