THE ROLE OF DNA IN CANCER RISK
LUCY A. GODLEY, MD, PHD • NORTHWESTERN MEDICINE SCIENTIFIC ADVISORY BOARD MEMBER
Virtually every cancer patient and family touched by cancer has asked: “Why me? Why my family?” And many times, doctors have answered: “Bad luck”, or “We don’t know”. But that answer is changing as we study people who have had cancer and people from large population cohorts. It turns out that a lot of cancer risk is built right into our DNA. WE USED TO THINK THAT INHERITED CANCER RISK WAS RARE, BUT WE NOW APPRECIATE THAT AT LEAST 5% OF BREAST CANCERS, ABOUT 5% OF COLON CANCERS, AND BETWEEN 10-20% OF BLOOD CANCERS ARE DRIVEN BY INHERITED DNA CHANGES. In total, probably about 10% of all cancers are due to these inherited DNA variants. Many of these inherited cancer predisposition conditions increase a person’s risk to several cancer types, and many of them are well known to the general public. Genes like BRCA1 and BRCA2 have had a lot written about them in the lay press, but there are many others.
How would someone know if they have inherited risk to cancer? The only way to know if someone has an inherited risk for cancer for sure is to do genetic cancer risk testing. Because many of these conditions give risk to several tumor types and because many people do not know their family histories very extensively, testing individuals using a broad panel of genes facilitates comprehensive testing. When we use these broad panels, we sometimes identify multiple inherited risk factors in a person/ family. If people are interested in this type of testing, they can contact their insurance company to find a cancer genetic counselor within their network and/or find a local cancer genetic counselor by visiting the NATIONAL SOCIETY OF GENETIC COUNSELORS website @ FINDAGENETICCOUNSELOR.NSGC.ORG.
WHY ME? WHY MY FAMILY?
So, who should be tested for inherited cancer risk? There are guidelines for which cancer patients should have inherited cancer risk testing, but if we accept that 10% of all cancers are likely inherited, then one can argue to test everyone with cancer. If people are concerned about their family history of cancer, they can seek testing. And thinking at the population level, when we look at known inherited cancer risk factors, we can see them in about 5% of some populations, which some would argue justifies inherited cancer risk testing in all people, regardless of personal or family history of cancer. Time will tell how broadly testing recommendations will extend, so for now, testing should take place for certain cancer diagnoses, especially if they are diagnosed at a young age for a particular tumor type and in people with strong family histories. Why does testing matter? For one, sometimes we alter treatment based on the presence of one of these conditions, especially if they affect someone’s ability to tolerate standard chemotherapy doses. ONCE A CANCER PREDISPOSITION CONDITION IS RECOGNIZED IN A PERSON/FAMILY, WE CAN EMPLOY A PERSONALIZED SCREENING PLAN TO SURVEY FOR CANCER OVER TIME THAT TYPICALLY COMBINES IMAGING TESTS AND BLOOD WORK. The goal is to identify tumors at very early stages, allowing definitive surgery to remove them. In the future, we might even be able to use a blood test to screen for multiple cancers in people at high risk, and ideally, we might be able to give people a medicine to slow or prevent cancer from developing in the first place. So, if you have wondered: “Why me?” “Why my family?”, consider inherited cancer risk testing of your DNA. Your risk may have started right there.
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