Genetic testing is becoming cheaper and more widespread, promising to usher in a revolution in cancer treatment. Yet, long-standing DNA tests are often overlooked for reasons including doctors’ ignorance and financial incentives discouraging companies from marketing them.
Fifty years ago, Henry T. Lynch, then a medical resident in Nebraska, started tracking families with a high incidence of colon cancer and other tumors. While some were skeptical when he suggested the risks were inherited, geneticists proved him right in the mid-1990s by finding the genes that caused the condition. Lynch syndrome may account for about 3 percent of all colon cancer, or more than 4,000 cases a year in the U.S., said Heather Hampel, an Ohio State University genetic counselor.
A test for Lynch syndrome costs as little as $300. Still, only about 50,000 people have been diagnosed with the disease of 800,000 afflicted with it, according to Linda Bruzzone, president and founder of Lynch Syndrome International, a patient advocacy group.
“There are people dying needlessly,” Lynch, now 84 and director of the Hereditary Cancer Center at the Creighton University School of Medicine in Omaha, Nebraska, said in a telephone interview. “That is the horror of it.”
As scientists predict DNA testing will transform medicine, doctors and hospitals are ignoring existing tests that could help prevent thousands of cancer deaths, not just of their own patients, but in generations to come.
Busy primary-care doctors, who typically have little training in genetics, don’t see the warning signs in patient family histories and don’t refer those at risk to a genetics expert. Testing companies don’t advertise and market some DNA tests as much as they do more lucrative tests for breast cancer genes, Bruzzone said.
This failure to incorporate genetic knowledge into routine prevention and treatment of diseases like colorectal cancer — the second-most common cause of cancer death in the U.S. –shows how hard it is to bring the benefits of the genome to patients.
“Lynch syndrome has been around for so many years, and we’re still not prepared to tackle it,” Fay Kastrinos, director of the hereditary gastrointestinal cancer program at Columbia University Medical Center in New York, said in a telephone interview.
Colleen Carroll learned that painfully. In 2002, Carroll, a computer programmer from Plainville, Connecticut, was diagnosed at the age of 36 with ovarian cancer, the same disease that killed her sister six years before. Her grandfather and two of his siblings earlier died of colon cancer.
Both types of cancer, and several others, are linked to Lynch syndrome, which speeds up tumor growth. Nevertheless, Carroll’s doctors never ordered a genetic test for it.
If they had, Carroll’s cousin might have been helped. She could have then undergone screening to spot cancer early or had her ovaries and uterus removed to prevent tumors in those organs. Instead, Carroll’s cousin died in 2006 at age 47 from ovarian and endometrial cancer.
“My cousin’s life could have been saved had I had the appropriate test,” Carroll, wrote to her doctors at Saint Francis Hospital and Medical Center in Hartford, Connecticut. “It is a horrible feeling.”
No company has exclusive rights to Lynch syndrome gene testing, and several companies offer the tests, including Myriad Genetics Inc. (MYGN) and Ambry Genetics Corp.
As is often the case with generic drugs, companies are reluctant to pay for large marketing campaigns because of concern their efforts might not boost use of their own proprietary tests, Bruzzone said in a telephone interview. Consequently, many doctors don’t know the dangers of Lynch syndrome, she said.
“No company has enough of the market share to make it worthwhile to invest in education of doctors and patients,” Bruzzone said. “Without a strong base, you can’t get anything done.”
Sales from Myriad’s tests for Lynch and other hereditary colon cancers represented 9 percent of the company’s revenue in the year ended in June, versus 82 percent from its patent- protected tests for the BRCA1 and BRCA2 breast cancer genes.
Myriad and Ambry officials deny they skimp on marketing their colon-cancer gene tests.
Myriad “has invested substantially” in marketing and education for its Lynch syndrome test, which it has sold since 2000, said Mark Capone, president of Salt Lake City-based Myriad’s genetic-testing unit. He blamed complicated medical guidelines for Lynch syndrome tests, often involving a two-step testing process, and low patient awareness of colon cancer for underuse of the test.
Ambry Genetics, based in Aliso Viejo, California, markets Lynch syndrome testing to doctors and counselors through trade shows, conferences and talks, said Kurtis Glade, marketing director. Awareness of many genetic tests is relatively low among physicians, he said.
“We’re working to close that gap as much as we can with education,” he said in a telephone interview.
Doctors typically learn about new tests through a combination of scientific studies showing tests save lives, recommendations from specialist groups, and marketing and education sponsored by testing companies.
Unaware of the Lynch test, many primary-care doctors fail to see the warning signs in patient family histories like Carroll’s and don’t refer those at risk to a genetics expert, said Lynch, who continues to promote awareness of the condition he identified five decades ago.
Tracking down related cancers through scattered family members, finding tissues samples and ordering the genetic test can be “a hell of a lot of work” for busy physicians, Lynch said. “It doesn’t pay sufficient funds to warrant the excess of time.”
Even when doctors suggest testing, patients may forgo it for fear of stigma, although a 2008 law forbids employers and health insurers from discriminating on the basis of their DNA.
“There is a lot of fear and anxiety and apprehension” among patients, Lynch said. In some families known to carry Lynch syndrome, some relatives still put off getting the test for a decade or more, he said.
Claiming almost 50,000 lives in 2011, colorectal cancer cases often have no symptoms at early stages. More than 90 percent occur in people older than 50, according to the American Cancer Society.
Patients with Lynch syndrome have flaws in one of four major genes that are involved in repairing DNA. As a result, precancerous growths in the colon, called polyps, can quickly turn deadly. Cancers in the endometrium, small intestine, stomach and ovaries can also grow unchecked.
About half of people with Lynch syndrome develop colon cancer by age 70, and as many as one-quarter of women with the condition develop ovarian cancer by that age, according to a 2011 study in the Journal of the American Medical Association. Affected women often have their ovaries and uterus removed after having children to prevent endometrial or ovarian cancer, and patients are told to have annual colonoscopies, which can prevent many deaths, said Richard Boland, a gastroenterologist at Baylor University Medical Center in Dallas.
In 2009, a study group sponsored by the U.S. Centers for Disease Control and Prevention recommended that everyone diagnosed with colon cancer should be offered testing to detect Lynch syndrome. Any relatives of patients who are positive for the defective genes should also be tested to prevent further cases, the panel said.
Still, just 42 percent of hospitals with cancer programs routinely screen colon cancer patients for the condition, according to a survey published this year in the Journal of Clinical Oncology. A separate study of 1,220 colon cancer patients found that only 5 percent got genetic testing for Lynch syndrome.
Doctors refer twice as many patients for investigation of possible inherited breast cancer to Houston’s MD Anderson Cancer Center than for possible hereditary colon cancer, even though the two are equally as common, said Patrick Lynch, a gastroenterologist at the center and the son of Henry Lynch. Colon cancer lacks the awareness that big-name charities like the Susan G. Komen for the Cure can give, he said.
“I talk to a lot of doctors, and most of them do not know what it is,” Neil Perlman, an internist in the Chicago suburb of Lincolnshire, said about Lynch syndrome.
Perlman knew little about the condition until 2009, when he was diagnosed with Lynch-related colon cancer at 44. His younger sister died of colon cancer in 2008, and his older sister had been found to have early uterine cancer in 2005. Before that, his mother had developed colon cancer in her early 50s.
Perlman had to have most of his colon removed and six months of chemotherapy. His cancer might have been diagnosed earlier, avoiding some of the heavy-duty treatment, had he or his sisters’ doctors understood the signs of Lynch syndrome in the family, he said. And his younger sister’s cancer might have been detected when it was more treatable, Perlman said.
It was frustrating that he and his sister went to good doctors and didn’t learn about the possibility of Lynch syndrome, Perlman said.
When Traci Leopold started feeling a dull pain in her belly in 2002, she suspected it might be something serious. Her father and grandmother had died of colon cancer, and her uncle had suffered from it.
After a visit to her primary-care doctor, she was prescribed an anti-reflux medication for a hernia, she said. Months later, as the pain got worse, Leopold insisted on getting referred for a colonoscopy that revealed a rapidly spreading tumor. Leopold won’t name her former primary-care doctor.
Even then, her treating doctors never tested her for Lynch syndrome. It wasn’t until 2005, more than two years after Leopold donated tissue for an Ohio State University genetic study, that the culprit emerged. The results showed Leopold had Lynch syndrome.
“If they weren’t doing this study, I still wouldn’t know about Lynch syndrome,” said Leopold, a 39-year-old mother of two boys in Columbus, Ohio. “Genetics never came into my mind until they tested me.”
Richard Sheets, the gastroenterologist who performed Leopold’s colonoscopy, said he wasn’t aware of her family history when he first saw her. Once the tumor was found, the first focus was on treating it, not genetics, he said.
While doctor knowledge of Lynch syndrome has improved since then, “there is no doubt that awareness is not where it needs to be yet,” he said.
Today, with her cancer in remission, Leopold receives annual colonoscopies, ultrasounds and other screening tests to spot new tumors before they spread. She also plans to make sure her sons get tested when they’re teenagers.
Since 2001, the average cost of deciphering a full human genome — the complete instructions for building the body — has dropped from $100 million to less than $10,000, according to the National Human Genome Research Institute. Testing for Lynch syndrome ranges from as little as $300, when the exact mutation that runs in the family is known, to as much as $4,000 when the mutation is unknown and multiple Lynch-causing genes need to be analyzed.
When Colleen Carroll got ovarian cancer back in 2002, the only genes her doctors tested were BRCA1 and BRCA2, both widely known to be linked to breast and ovarian cancer. Those tests were negative. One doctor told Carroll, now 46, that her ovarian disease was a case of “lightning striking twice,” she recalled.
“I should have been referred to a genetic counselor,” Carroll said.
Carroll’s testing for these breast cancer mutations isn’t surprising, Bruzzone of Lynch Syndrome International said. Doctors and patients are well aware of the link between the BRCA genes and ovarian cancer because Myriad Genetics markets its patented test heavily, she said.
Hospital officials declined to comment directly on Carroll’s case. At the time she was treated, Saint Francis didn’t have cancer genetic counselors on staff, said Tina Varona, a spokeswoman. A program was established in 2010. The hospital’s protocols followed “the latest evidence-based procedures available at that time,” and some clinicians had supplementary genetics training starting in 2002, she said in an e-mail.
“In the early years of Lynch syndrome, everyone’s focus was much more on the colon cancer,” said Jonathan Sporn, chief of hematology/oncology at Saint Francis. “The potential role of non-colon cancer was not as emphasized as it is now.”
Carroll survived because she had a less aggressive tumor that was caught and treated promptly.
Her cousin, Deborah Raboin, wasn’t as lucky.
In 2005, Raboin developed simultaneous ovarian and endometrial cancer. She was also treated at Saint Francis Hospital and was seen by at least one of the same doctors as Carroll. No one thought to test Raboin for Lynch syndrome, said her sister Karen Zeena.
It wasn’t until after Raboin died in 2006 and her father developed intestinal cancer that he was finally tested for Lynch syndrome by genetic counselor Ellen Matloff at Yale Cancer Center. The positive test led to screening of other family members, several of whom have been found to have Lynch syndrome genes. Carroll’s two nieces, the daughters of Carroll’s sister who died of ovarian cancer, have been screened and found to have Lynch syndrome genes.
“I feel like there were all these dots out there and nobody was connecting them,” Zeena said.
To contact the reporters on this story: John Lauerman in Boston at firstname.lastname@example.org; Robert Langreth in New York at email@example.com
To contact the editor responsible for this story: Jonathan Kaufman at firstname.lastname@example.org
- Lynch Syndrome (familyhistorybowelcancer.wordpress.com)
- Preoperative Testing For Lynch Syndrome Yields ‘Huge’ Benefit (familyhistorybowelcancer.wordpress.com)
- Lynch Syndrome and other non-polyposis inherited cancer syndromes (familyhistorybowelcancer.wordpress.com)
- JAMA: Identification of Lynch Syndrome Among Patients With Colorectal Cancer (familyhistorybowelcancer.wordpress.com)
- Less than 10% of bowel cancer patients at high risk of Lynch Syndrome are screened for the condition | Beating Bowel Cancer (familyhistorybowelcancer.wordpress.com)
- My Semicolon Life: Tracing my family’s cancer history – by Brian Mansfield (familyhistorybowelcancer.wordpress.com)
- Lynch Syndrome and Uterine Cancer Risk (everydayhealth.com)