Not long ago, we were all focused on Angelina Jolie's breasts. Or more specifically, on the removal of Angelina Jolie' breasts. Angelina’s decision to surgically sacrifice not only the breast harboring a malignancy but also her other, perfectly healthy breast landed her on the cover of Time Magazine and was widely covered in the media. Angelina willingly gave up her healthy breast, we learned, because she had a “genetic mutation" that greatly increased her risk of developing breast cancer.
I was recently approached by a young woman who had heard me speak on "Genomics and Personalized Medicine” during which I explained that simple genetic testing can identify some people who don’t respond to certain drugs or standard drug doses. She had several months earlier suffered a life-threatening blood clot and had since been taking Coumadin®, a widely prescribed “blood-thinner” used to prevent blood clot formation. Yet despite steadily increasing doses to the maximum recommended, her doctor had been unable to adequately "thin her blood" and now feared moving to a higher dose. Thus, she remained under-dosed and at risk for a second life-threatening blood clot. I recommended a simple genetic test. She educated her physician and tested positive for a genetic mutation known to cause the rapid breakdown of Coumadin®, allowing her to finally be dosed correctly at a dosage that would be very dangerous for most of us.
Clearly Angelina Jolie and this woman's stories demonstrate the rapidly growing importance of "Genomics & Personalized Medicine." Your genetic profile, called your genome, has enormous implications for your health, including your cancer risk and response to medications. And while technology is advancing so rapidly that my daughters will have their own individual genomes on their cell phones within the next decade, many doctors still don't understand what genetic tests should be used on which patients and when…
So, given that it's your body and your health, you should learn (and you are certainly smart enough).
So what's a genome? Or a genetic mutation? Or a gene?
With few exceptions, within every one of the more than 30 trillion cells in your body you have an identical copy of your personal DNA, called your genome. Think of your genome as The Book of You. Your genome is your genetic fingerprint, specific to you and only you, defining how you look (height, hair color, eye shape, number of toes, everything), in large part how how you think and act, your intelligence…everything that makes you you.
The Book of You, your genome, is broken down into 23 chapters, called chromosomes, filled with genetic words and sentences. And while English writing uses 26 letters, your genome uses only four letters, each representing one of the four chemical builiding blocks of DNA: A, T, C, and G. The Book of You is made by stringing these four letters together into a complete genome that is 3.1 billion letters long!
Within your 3.1 billion letter book, some sequential groups of letters are genes (words) and others are non-genes (punctuation) that turn on and off the genes. Like English words, some of your approximately 21,000 genes are short (for example, ATCTTAGCGT might mean that you’ll have brown eyes) and others are thousands of letters long. And like any book, the exact order of your 3.1 billion letters is unique to you, and the activity or inactivity of a single gene or combination of genes determines your hair color or your sense of smell or your musical talent or your kidney function.
Also like printed words, genes can have “typos,” errors called mutations, in which one or more of the letters is erroneously replaced by another letter or deleted. Most mutations have no consequence (just as leaving out the second “p” in “salt and peper” doesn’t keep you from understanding the phrase). But even some simple mutations dramatically impact your body, just as replacing “h” with “c” in "I put the hat in the closet" greatly alters the meaning (just ask your cat). Impactful mutations may significantly increase your risk for certain cancers and diseases, result in fatal congenital syndromes, or alter your body’s response to medications. Fortunately, to develop most cancers, at least one cell and its numerous, indentical daughter cells must accumulate multiple genetic mutations, usually over a long time. Thus, it takes years for multiple mutations to lead to a benign colon polyp and additional mutations and years for a cell within the polyp to become a colon cancer.
So how do you end up with genetic mutations? First, you can inherit a mutation that is present in the DNA of your mother's egg or your father's sperm (or both), just like you inherited the genes that lead you to share physical and personality traits with your parents and siblings. And that inherited mutation will be replicated in all of your cells throughout your life. Angelina’s greatly increased risk of breast cancer resulted from an inheritedmutation.
Second, you can acquire genetic mutations either spontaneously or due to behaviors which expose you to carcinogens, factors which promote genetic mutations and increase your risk of cancer. Remember, your over thirty trillion cells copy your 3.1 billion letter genome as many as 75 times during your lifetime. Thus, it’s not surprising that spontaneous errors occur, and that even your body’s amazing mechanisms to detect and repair these mutations fail on occasion. Our personal behavior can also damage our genome: Exposure of your normal genes to damaging carcinogens (cigarette smoke, ionizing radiation from the sun) can lead to cancer.
So, what's the practical takeaway?
First, don't assume that your doctor understands all (or even much) about genomics. Many have had little or no training on recent advances in how genetic testing can impact their patients. You must respectfully educate your physician partners.
Second, get a handle on your own genetic risks by talking with your biological mom, dad, brothers, sisters, and children. These “first-degree relatives” most closely resemble you genetically. Learn if and at what age any have been diagnosed with cancer or non-malignant serious conditions. Ask if they’ve ever had a serious response (or an inadequate response) to a medication. This simple "family history" empowers you and your physician in assessing your likelihood of having an inherited health risk and in understanding whether you should undergo simple genetic testing. Knowledge is power, and identifying a genetic mutation allows for aggressive screening and early diagnosis, or even preventative treatment (as in Angelina's case).
Today, we cannot identify any link between most health conditions and specific genetic mutations.
But ask again tomorrow. That's how fast we're learning.