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Q&A on Genetics and Cancer - Answers from oncologist Dr. Grace Makari-Judson

September 15, 2015
Dr. Grace Makari-Judson

By Dr. Grace Makari-Judson, Gazette Contributing Writer

(Published in print in The Daily Hampshire Gazette: Tuesday, Sept. 15, 2015)

Cancer begins in our cells, the building blocks of the body, when mutations occur to the DNA within cells causing them to grow uncontrollably.

Today, thanks to research mapping the genes of cancer cells, doctors are learning more about the relationship between genetic changes and the development of cancer. While genetic testing is already changing the way patients and doctors deal with cancer, in the years ahead there is no doubt that its role will be even greater in the discovery and treatment, as well as predicting a person’s risk of cancer.

While no test can predict when and if you will have cancer, teams of certified genetics counselors and medical oncologists can give patients the information they need to make the best decisions for their future health.

Q. What role does genetics play in the development of cancer?

A. We often think of cancer as a disease of aging. Every time a cell divides, there is an opportunity for error, and this can lead to cancer. Some cancers are associated with mutations in tumor suppressor genes. These genes are like the brakes of a car. If the main brake is not functioning, the emergency brake takes over. But if both brakes are out, the car crashes and cancer develops.

Individuals who have inherited certain mutations are born with one brake already out. In these people, it may not take long for the emergency brake to malfunction, leading to the diagnosis of cancer, usually at a younger age than the general population.

Q. What have oncologists learned over the years about the genetics of cancer?

A. The term genetics does not just apply to the genes that an individual has inherited, but also to the genetic makeup of a tumor. A mutation that an individual was born with is referred to as a "germline" mutation. However, tumors can acquire mutations which are referred to as "sporadic" mutations.

Some tumors are estimated to have up to 10,000 mutations. Not all these mutations are ones that oncologists can target with drugs, but increasing numbers of cancers do have mutations that can be targeted with specific treatments.

Q. What types of cancers have the strongest genetic link in terms of family history?

A. There are a few very rare cancers that have a genetic link, but the most common hereditary cancers are seen in families with breast, ovarian and colon cancers.

Still, only a minority of cancers are related to heredity. For example, in women with a diagnosis of breast cancer, less than 20 percent are related to family history.

Q. How big a role does genetic testing play in the diagnosis and treatment of cancer?

A. A diagnosis often prompts people to learn more about their family histories and this may lead to an individual finding out that he or she has inherited a cancer-susceptibility gene. The treatment of cancer, in most cases, is not different in those who have an inherited mutation. However, these individuals may be at higher risk for second cancers and this fact may influence treatment decisions.

There are new classes of drugs targeting specific mutations that are used in advanced ovarian cancer called PARP inhibitors. At the Baystate Regional Cancer Program, we have clinical trials looking at the use of PARP inhibitors in some women with breast cancer due to BRCA1 or BRCA2 mutations.

Q. Who should consider testing?

A. Testing can be considered in individuals who have multiple family members with cancer on the same side of the family, especially if the cancers are occurring at young ages, if one individual has multiple cancers, or if cancer occurs in an unexpected setting, such as breast cancer in a man.

Testing is more meaningful if it is performed first on an individual in a family who has a member with a cancer diagnosis. Unfortunately, cancer is common, so it is not uncommon to have a relative with cancer. We need to keep in mind that many other factors may contribute to cancer susceptibility like smoking, obesity and certain viruses.

While genetic testing may help to identify individuals at higher risk for cancer, a negative genetic test, unfortunately, does not mean that someone will never get cancer.

Q. What do positive results mean for both the patient and their doctor?

A. Identifying individuals with known mutations provides an opportunity to prevent cancer. Strategies include more intense surveillance, for example, MRI to watch for breast cancer or colonoscopy to watch for polyps. Risk-reducing medications are also discussed. Some individuals will also consider preventative surgeries.

Q. What does the future hold for cancer genetics?

A. The widespread availability of genetic testing has raised many questions and brought on new ethical dilemmas.

Direct-to-consumer testing is widely available and is often performed without adequate counseling. For some genes, such as BRCA1/2 associated with breast cancer, there is good research to guide individuals in decisions about reducing their risk.

However, some results are not so easy to interpret. The more genes that are tested, the higher the likelihood of finding a "variant of uncertain significance" (VUS). When these results are reported, it is suggested that individuals enroll in national databases that, hopefully, will ultimately shed light on the significance of these findings.

Although we may be able to test for a multitude of genetic mutations, our ability to do the tests has outpaced our understanding of many of these results. This can lead to anxiety, or worse, an unwarranted decision to consider preventative surgery.

It is extremely important that before considering genetic testing, an individual is properly counseled about the possibility of a positive test, a negative test and a VUS. The Family Cancer Risk Program at the Baystate Regional Cancer Program takes a team approach to advising individuals on whether or not to consider testing, which test to have done, and if it is the right time in their lives to consider testing and act upon the results. Family history and cancer screening still matter whatever the test result.

Dr. Grace Makari-Judson is chair of Baystate Health Breast Network and medical director of the Family Cancer Risk Program at the Baystate Regional Cancer Program based in Springfield.