National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
February 21, 2012 • Volume 9 / Number 4

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Featured Article

Routine Lynch Syndrome Screening Varies at U.S. Cancer Centers

An enzyme encircles the double helix to repair a broken strand of DNA (Illustration by Tom Ellenberger, Washington University School of Medicine)An enzyme encircles the double helix to repair a broken strand of DNA. Without molecules that can mend such breaks, cells can become cancerous. Mutations in genes that regulate this DNA repair system are a hallmark of Lynch syndrome. (Illustration by Tom Ellenberger, Washington University School of Medicine)

Screening practices for a condition called Lynch syndrome, which increases the risk of colorectal, endometrial, and other cancers, appear to vary substantially among different clinical centers in the United States, according to a new study.

Clinical guidelines developed by several different groups recommend routinely screening tumor samples from patients newly diagnosed with colorectal cancer for genetic markers of Lynch syndrome, although they differ with respect to exactly which patients should be screened (see Table). In the study—published online February 20 in the Journal of Clinical Oncology, and the first to attempt to assess current screening practices for the condition—only 42 percent of the responding centers reported that they conducted any routine screening for Lynch syndrome. Another 16 percent reported that they planned to do so.

NCI-designated comprehensive cancer centers—most of which are large academic medical centers that provide clinical cancer care and perform basic and clinical research—were far more likely than smaller hospitals and community cancer programs to perform this testing, the study showed.

In conducting the NCI-supported study, researchers from the City of Hope Cancer Center and Ohio State University Comprehensive Cancer Center surveyed all 39 NCI-designated comprehensive cancer centers that provide adult oncology care, a random selection of hospital-based cancer centers accredited by the American College of Surgeons, and a randon selection of community-based cancer programs. Of the 24 NCI-designated comprehensive cancer centers that responded to the survey, 71 percent reported that they routinely screened tumor samples from colorectal cancer patients, known as reflex testing. By comparison, only 15 percent of smaller community-based cancer programs reported doing so.

"Like any new practice, routine screening for Lynch syndrome will take time to be widely adopted," said the study's senior author, Dr. Deborah MacDonald of the Division of Clinical Cancer Genetics at City of Hope. "I think it's becoming more common, but it's clearly something that providers and institutions need to become more educated about."

Identifying All at Risk

Also known as hereditary non-polyposis colon cancer, Lynch syndrome is caused by mutations in several genes involved in a DNA repair process called mismatch repair (MMR, see video). The familial syndrome accounts for 2 to 4 percent of colorectal cancer cases; these and other Lynch syndrome-related cancers typically occur in people aged 50 and younger. (See the related article in this issue.)

Identifying Lynch syndrome-related cancers is important for multiple reasons, said Drs. MacDonald and Laura Beamer, the study's lead author. A diagnosis of Lynch syndrome can influence how much of the colon is removed during surgery, and women may opt for a hysterectomy, as well as removal of the ovaries, to reduce the risk of Lynch syndrome-related endometrial and ovarian cancers.

The larger impact, said Dr. Michael Hall, director of the Gastrointestinal Risk Assessment Program at Fox Chase Cancer Center in Philadelphia, may be on post-treatment surveillance for Lynch syndrome-related cancers, and on patients' close family members, who have up to a 50 percent chance of having the condition and may require more intense cancer screening than the general population.

"That's a critical point," said Dr. Hall. "This screening process allows us to identify many more people with an increased cancer risk."

A Complex Undertaking

Testing typically involves one or two different methods—DNA microsatellite instability (MSI) testing and immunohistochemistry (IHC) testing—to identify molecular changes that suggest MMR gene mutations. If these tests detect abnormalities, DNA mutational analyses are typically done to determine whether MMR gene mutations are present.

Just as clinical guidelines differ with respect to exactly which patients should be screened for Lynch syndrome, cancer centers—even the largest centers—differ in how they approach screening, the study found.

Some responding comprehensive cancer centers used the IHC test only, others used the MSI test only, and some used both. At City of Hope, tumor samples from all newly diagnosed patients younger than 60 are screened using the IHC test, with MSI testing performed as well in certain circumstances. At Ohio State, which has been at the forefront of Lynch syndrome screening, all newly diagnosed cases of colorectal cancer, regardless of the patient's age, have been screened using the IHC test since 2006.

"I do anticipate that things will become more uniform in the future as additional studies help elucidate the best, most cost-effective screening protocol," said study co-author Heather Hampel of the Clinical Cancer Genetics Program at Ohio State.

Regardless of a center's size, establishing a process for Lynch syndrome reflex testing is a complicated undertaking, and the process may take a year or longer, noted Dr. Hall. Decisions must be made about how samples will be tested and how positive screening results are communicated to patients. Not surprisingly, smaller centers, which often have fewer resources for laboratory testing or genetic counseling, can have more difficulty establishing a screening program.

And even when reflex testing is performed, there is no guarantee that the intended result, identifying people with Lynch syndrome, will be achieved, Dr. Hall stressed. "A big part of it is how many patients actually come in and get genetic counseling and have the genetic test performed," he said. In a 2009 Ohio State study, for instance, only about one-quarter of patients with suspected Lynch syndrome based on IHC testing made an appointment with a genetic counselor to follow up on the findings.

In an effort to improve the study and establishment of universal screening programs, Ms. Hampel and representatives from three other institutions recently launched the Lynch Syndrome Screening Network. Network leaders have developed a database to anonymously track screening outcomes, as well as educational materials for cancer programs trying to initiate universal screening, Ms. Hampel said.

Clinical Guidelines on Screening for Lynch Syndrome

Revised Bethesda Guidelines2004Developed as a result of NCI-sponsored workshops
Evaluation of Genomic Applications in Practice and Prevention2009Recommendations from Centers for Disease Control and Prevention working group
National Comprehensive Cancer Network Guidelines on Colorectal Cancer Screening2011Free registration required


—Carmen Phillips

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