As an American Studies major at Georgetown University, Claudia Gilmore had plenty of experience taking exams. But at the age of 21, she faced an altogether different kind of test—and no amount of studying could have prepared her for the result.

Gilmore had decided to be tested for a mutation in a gene known as BRCA1. Specific mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast and ovarian cancers.

Gilmore’s grandmother had battled breast cancer and later died from ovarian cancer. Before her death, she had tested positive for the BRCA1 mutation. Her son, Gilmore’s father, was tested and discovered he had inherited the mutation. After talking with a genetic counselor to help her understand the implications of the test, Gilmore gave a sample of her own blood and crossed her fingers.

Mutations that increase the risk of developing a particular disease are called genetic risk factors.

“I had a fifty-fifty chance of inheriting the mutation. I knew there was a great possibility it would be a part of my future,” she says. “But I was 21, I was healthy. A part of me also thought this could never really happen to me.”

Unfortunately, it could. Two weeks after her blood was drawn, she learned that she, too, carried the mutated gene.

Genetic testing is becoming increasingly common—in some cases, even routine. In 2003, after 13 years of painstaking work, scientists published the first draft of the complete human genome. The human genome consists of the DNA in one complete set of 23 chromosomes. It contains about 3 billion base pairs, the structural units of DNA. In the years that followed, much attention has been placed on understanding the genetic differences between individuals.

In reality, there isn’t one single human genome. Everyone on Earth (with the exception of identical twins) has his or her own unique genetic sequence. Your personal genome, consisting of two sets of chromosomes, is the blueprint that codes for your hair color, the length of your nose, and your susceptibility to certain diseases. On average, any two human genomes are 99.9% identical, meaning that they differ at about 3 million base pairs.

Oftentimes, those differences have no impact on health. In some cases, however, a particular genetic signature is associated with disease. Sometimes a gene mutation makes a given illness inevitable. Certain mutations in a gene called HTT, for instance, always result in Huntington’s disease, a degenerative brain condition that usually appears in middle age.

The link between mutations and disease isn’t always so clear-cut, however. Most genetic diseases are complex in origin, and it may take multiple genetic mutations, as well as other non-genetic factors, for the disease to develop. Mutations that increase the risk of developing a particular disease are called genetic risk factors.

Certain mutations in the BRCA1 and BRCA2 genes are known genetic risk factors for breast and ovarian cancers, for instance. But not everyone with these mutations develops cancer. According to the National Cancer Institute, about 60% of women with a harmful BRCA1 mutation will develop breast cancer in her lifetime, compared with about 12% of women in the general population. And 15% to 40% of women with a BRCA1 mutation will be diagnosed with ovarian cancer, compared with just 1.4% of women without that genetic change.

The BRCA1 mutations are just some of the thousands of harmful genetic changes that geneticists have identified so far. Other common mutations have been shown to elevate one’s risk of developing heart disease, diabetes, various cancers, and numerous other common illnesses. Often, these mutations involve changes to just a single base pair of DNA. These common single-letter mutations are known as single nucleotide polymorphisms, or SNPs.

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Genome sequencing technology has improved significantly over the last decade, making it easier and less expensive to scan an individual’s DNA for potentially harmful SNPs. A number of companies now offer genetic tests directly to the public. Unlike tests such as the BRCA1 blood test that Gilmore was given, these direct-to-consumer (DTC) tests are offered to customers without any involvement of a medical professional, at a cost of a few hundred dollars.

Some of these tests aren’t related to health at all. Your personal genome contains many unique features—from the shape of your fingernails to the shade of your skin—that don’t affect your health but make you the person you are. Some DTC testing services aim to tell customers about their history by screening genes to identify variations that are more common in certain geographical regions or among members of certain ethnic groups. One such company offers genetic tests to African-Americans to determine in what part of the African continent their ancestors originated.

Other popular DTC tests inspect DNA samples for SNPs associated with certain diseases and physical traits—everything from Parkinson’s disease and age-related macular degeneration to earwax type and propensity for baldness.

Advocates of the tests say the technology puts the power of genetic information in the hands of consumers. Critics, on the other hand, argue that the information provided by DTC tests isn’t always very meaningful. The presence of some SNPs might raise the risk of a rare disease by just 2% or 3%, for example. In many cases, the precise link between mutation and disease is still being sorted out. Also, without input from a genetic counselor or medical professional, consumers may not know how to interpret the information revealed by the tests. The American Medical Association has recommended that a doctor always be involved when any genetic testing is performed.

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Moreover, knowing your genetic risk factors isn’t the whole story. When it comes to your health and well-being, the environment also plays a significant role. Someone might override a genetic predisposition for skin cancer by using sunscreen faithfully every day. On the other hand, a person might have a relatively low genetic risk for type 2 diabetes, but still boost the odds of developing the disease by eating a poor diet and getting little physical exercise.

Claudia Gilmore is especially careful to exercise regularly and eat a healthy diet. Still, she can only control her environment to a degree. She knew that, given her genetic status, her risk of breast cancer remained high. She made the extraordinary decision to eliminate that risk by undergoing a mastectomy at the age of 23. It wasn’t an easy decision, she says, but she feels privileged to have been able to take proactive steps to protect her health. “I’ll be a ‘previvor’ instead of a survivor,” she says.

Two years later the same medical choice was made by the American actress, film director, screenwriter, and author Angelina Jolie, who recounted her experience in the New York Times, writing, “Once I knew that this [BRCA1 mutation] was my reality, I decided to be proactive and to minimize the risk as much I could. I made a decision to have a preventive double mastectomy. I started with the breasts, as my risk of breast cancer is higher than my risk of ovarian cancer, and the surgery is more complex. . . . I am writing about it now because I hope that other women can benefit from my experience.”¹

For now, it’s still too costly to sequence every individual’s entire genome. But each year, many more genetic tests hit the market. Already, doctors are beginning to design medical treatments based on a patient’s personal genome. People with a certain genetic profile, for example, are less likely than others to benefit from statins, medications prescribed to lower cholesterol. Doctors are also choosing which cancer drugs to prescribe based on the unique genetic signatures of patients and their tumors.

We’ve only just entered the era of personal genomics. While there’s much left to decipher, it’s clear that each of our individual genomes contains a wealth of biological information. And, as Gilmore says, “I’ve always been taught that knowledge is power.”

CASE 3 QUESTIONS

Special sections in Chapters 12–20 discuss the following questions related to Case 3.