Just as cancer takes many forms, so does genetic testing. When a patient seeks genetic testing at UT Southwestern Medical Center in Dallas, Texas, they must first provide a detailed personal and family health history. “When their history includes early onset cancers or a specific constellation of cancers in multiple generations, my genetic counselors and I use the information to decide what genetic test to offer the patient,” says Theodora Ross, MD, PhD, professor of internal medicine.
By Marilynn Larkin
NEW YORK (Reuters Health) – Lynch syndrome puts patients, their immediate family and, according to new findings, also second- and third-degree relatives at increased risk for various cancers, researchers say.
Research has shown that Lynch syndrome predisposes individuals to colon, ovarian, endometrial and brain cancers. However, studies attempting to calculate risks to family members have been limited by selection bias, lack of confirmation of cancer diagnoses in relatives, and lack of population-based controls, according to Dr. Jewel Samadder of Mayo Clinic in Scottsdale, Arizona, and colleagues.
To overcome those limitations, the team analyzed data from a Utah population database of close to eight million individuals, combined with data from the state’s cancer registry records from 1996 to 2013. (Dr. Samadder was at the University of Utah when the study was conducted.)
From among 17,087 patients with colorectal cancer, they identified 202 families with 443 members whose cancers met Amsterdam I or II criteria for Lynch syndrome, including 59 that met both criteria (Amsterdam I criteria are more restrictive).
As reported in JAMA Oncology, online August 3, analyses of cancer risks in first-, second-, and third-degree relatives of patients with cancers that met both criteria showed increased risks for both common and rarer cancers.
Specifically, compared with the general population, first-degree relatives had risks that were 10 times higher for colorectal cancer, 7.7 times higher for cancer of the small intestine, 7.6 times higher for brain cancer, and 5.9 times higher for endometrial cancer.
Risks were also about twofold higher for cancers not normally associated with Lynch syndrome, including kidney, thyroid, non-Hodgkin lymphoma, and prostate cancers.
Second-degree relatives had a 4.3 times higher risk of developing colorectal cancer and a 2.7-fold increased risk for endometrial cancer, as well as less elevated risks for cancers of the small intestine, brain and liver.
Third-degree relatives had a nearly twofold increased risk of colorectal cancer and a 1.5-fold increased risk of endometrial cancer.
The authors suggest that the study “provides clinicians with population-based, unbiased data to counsel members of families meeting the Amsterdam criteria regarding their elevated risks of cancer and the importance of cancer screening.”
Dr. Howard Ross, Chief of the Division of Colorectal Surgery at Temple University Hospital, Philadelphia, said the risk to second-degree relatives is “a new warning and may help relatives who might have believed they were at the same risk as others not in Lynch families.”
“Practice will likely change,” he told Reuters Health by email, “in that awareness helps foster discussion in families and with health care providers.”
“Discussion lowers the apprehension for colonoscopy and minimizes the stigma of the test,” he added. “Being on the lookout for cancers not associated with the colon may help many people.”
Cancer geneticist Dr. Theodora Ross of UT Southwestern Medical Center, Dallas, Texas, told Reuters Health, “Their analysis of risks for specific cancers (is) one of the most robust ever and adds valuable data to the existing body of evidence we use when we talk with our patients with a family history of these cancers.”
“Another positive is that they did not have a definitive genetic diagnosis, and frequently physicians in real life also do not have a clear genetic diagnosis and need such data to support their recommendations to patients who are members of these cancer-prone families,” she said by email.
However, lack of a genetic diagnosis could also be a limitation, she noted, because the tumors may have been due to other hereditary cancer syndromes.
“Lynch syndrome is woefully underdiagnosed,” Dr. Ross continued. “Only a few percent of the individuals with Lynch syndrome who have not yet been diagnosed with cancer know they are at risk. Once a person is aware of their risk, colonoscopies, other surveillance, and preventative surgeries can save their life.”
“Many healthcare providers do not counsel third-degree relatives to take their cousin’s cancer seriously,” she observed. “This is an error. Thankfully, papers like this keep reminding us how important it is to educate laypersons and healthcare providers about why knowing your patient’s genetic inheritance can save their life.”
Our expert voices conversation on genetic testing for cancer.
Most people who have a genetic mutation that predisposes them to cancer don’t know it. They also aren’t aware they could act on that knowledge and make choices that could save their life. A seemingly ideal solution would be to make cancer genetic tests a primary care routine for all adults.
Here’s the problem: Genetic testing is imperfect and genetic care is still in its infancy.
A real solution: Prevention. Gain knowledge of your family’s cancer history. Stop smoking. Limit how much alcohol you drink. Exercise regularly. Get vaccinated.
Bottom line: Even without knowing our genetic test result, we can make concrete choices to help avert a future cancer.
The other voices in the conversation:
In her new book, “A Cancer in the Family: Take Control of your Genetic Inheritance,” Dr. Theodora Ross addresses how our family’s medical history plays a role in our health. To shed some light on the genetics of cancer, as well as genetic counseling, Ross spoke with “Take Care” to explain the importance of knowing your family history.
A couple of weeks ago, we published Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function by Theo Ross and her colleagues at UT Southwestern. Dr. Ross is a great example of a scientist who is doing both. She’s the author of a popular book about cancer, and she’s unafraid to say what’s on her mind.
Hidden cameras and the beauty of the scientific method.
“We don’t have enough genetic counselors. We don’t have enough doctors who understand genetics. So when people get genetic tests, they think, ‘Oh, it’s done. I’ve done it. I’m fine.’ But it’s not. It’s not a single event.
Can a blood test for cancer be a dangerous proposition? Depends on the test.
For one ovarian cancer patient, let’s call her Emily, treatment based on blood test results led to her premature death.
Can genetic testing help mitigate cancer risk? (Washington Post Live)
My sister, Bea, was 35 years old when she was diagnosed with breast cancer, and 38 years old when she died in 1993. She left behind a husband, two toddlers and, innocently, a genetic legacy that our family continues to confront today.