• Paths of Progress Fall/Winter 2010

    Genetic tests for cancer risk, demystified

    Judy garberJudy Garber, MD, MPH 

    If you could look into a crystal ball and see that you had a greater chance of developing certain cancers, you might make some changes today to lessen those odds.

    That is the theory behind the Friends of Dana-Farber Cancer Genetics and Prevention (CGP) clinic. There, under the leadership of co-directors Judy Garber, MD, MPH, and Sapna Syngal, MD, MPH, clinicians and researchers analyze people's germline DNA – the genetic code inscribed in every cell in the body – searching for specific inherited gene mutations that are known to increase the risk of developing certain cancers.

    After determining a person's likelihood for cancer, the CGP team helps individuals with an increased risk take precautionary measures, such as receiving frequent screenings, taking certain medications, and adopting a healthier lifestyle, to help ward off cancers before they materialize.

    This approach is deeply rooted, as Dana-Farber researcher Frederick Li, MD, was among the first to introduce the concept, in the 1960s, that cancer risk could be inherited.

    Considered a father of cancer genetics, Li discovered that a germline DNA mutation of the p53 tumor-suppressor gene, which normally helps control cell growth, was linked with increased cancer risk in families with the inherited cancer syndrome that bears his name, Li-Fraumeni syndrome.

    His findings sparked other investigators worldwide to search for inherited cancer genetic alterations, many of which have since been identified, including those that cause certain breast cancers (such as the BRCA1 and BRCA2 genes), gastrointestinal tumors (colon, pancreatic, and gastric), and other cancers.

    Today, about 5 percent of cancers result from an inherited predisposition to cancer, and CGP leaders say there are many more cancer genes still to be discovered. This is one reason the CGP clinic will expand into its own clinical center when Dana-Farber's Yawkey Center for Cancer Care opens in early 2011.

    "In addition to identifying people at higher risk for developing cancers, we'll focus on pharmacogenetics," says Garber, director of the new treatment center.

    "We're learning about how people's genetic endowment can influence who is more likely to benefit from certain treatments and who is likely to experience particular side effects."

    The CGP clinic currently sees about 1,200 new people a year, around 10 percent of whom have cancer-causing mutations. Some have had a cancer diagnosis; others are hoping to avoid cancer for themselves and their relatives.

    Garber says the prime candidates for genetic testing are people who are diagnosed with cancer at an early age, or whose relatives had cancer at a young age or had multiple or rare tumors.

    Claire Cormier was one such person.

    "My sister had just undergone surgery for breast cancer at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) when she read that researchers there were seeking volunteers to be screened for pancreatic cancer," says Cormier, 74.

    "Since both our mother and brother had died of pancreatic cancer, we enrolled. I found that I carry a mutation in the BRCA2 gene [which is associated with breast and other cancers], but my sister did not."

    Cormier, a mother of four and grandmother of nine, had her ovaries and fallopian tubes removed to reduce her risk for ovarian cancer, which has been linked to BRCA2 mutations. She also has yearly scans of her pancreas to check for changes there. So far, the efforts are working.

    "It's exciting to see people with a strong family history of cancer who are living cancer-free," says Katherine Schneider, a genetic counselor at DF/BWCC.

    "They may have had parents, an aunt, or uncle who died of the same disease, but with proper screening, they are surviving."

    One strong benefit of the CGP clinic is that genetic counselors meet directly with patients to report genetic findings and recommend medical next-steps.

    Sapna Syngal and Claire CormierSapna Syngal, MD, MPH, talks with a patient 

    For example, explains Syngal, director of the Familial Gastrointestinal Cancer Program at DF/BWCC, if a patient's brother had colon cancer and then the patient developed the disease, they might recommend surgically removing more of the patient's colon to prevent a future cancer.

    "One of the biggest mistakes we see is when doctors don't recognize that someone has an inherited cause of their cancer, and they don't recommend the more intensive monitoring necessary for people with genetic risk, who also have a greater chance of getting more than one cancer," says Syngal.

    "A patient might say to a doctor, 'I don't feel comfortable coming back in five years,' and the doctor says, 'five years is fine,' because that is fine for 95 percent of the population – but it's not the best course for someone with a genetic predisposition to a disease."

    Genetic Counselor Monica Dandapani adds, "Some people may still be at increased risk because of family history, even if they're not in the high-risk genetic category. These people still need additional screening based on family history. We try to come up with a screening plan that makes sense."

    While there are many who find comfort in knowing whether or not they are genetically predisposed to cancer, there are those who prefer the uncertainty. They don't want to be tested because they think it will change how they think about themselves or their family.

    Others would rather hope that they are negative than learn that they are positive.

    "People are not 'sick' just because they find out they have an altered cancer gene," Garber says. "It's best when the genetic information empowers people to take control of their lives. This information can help you change a legacy of cancer into a legacy of activism."

    Even for people with a strong family history of cancer who do not want to be tested, there are still screening and prevention opportunities. CGP staff encourages such individuals – and others – to visit the clinic and learn about their options.

    "Risk and prevention is a piece of cancer that is often left behind," says Syngal. "It's much sexier to find cures for cancer, but it is at least as important to try to prevent it."

    Paths of Progress Fall/Winter 2010 Table of Contents

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    • Read more about cancer care and research at Dana-Farber in the Fall/Winter 2010 issue of Paths of Progress.