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Sapna Syngal, MD, MPH
A new study has documented a nine-fold higher risk of pancreatic
cancer in individuals with Lynch syndrome, a rare genetic cancer
predisposition syndrome, report scientists from the Dana-Farber Cancer
Institute and the University of Michigan.
The study, published in the Oct. 28 issue of the Journal of the American Medical Association,
is the first using rigorous statistical methods to confirm the elevated
risk, the authors say. Previous studies yielded conflicting results.
"In light of these findings, we believe that if you have Lynch
syndrome and there is pancreatic cancer in your family, you should be
closely monitored," said Sapna Syngal, MD, MPH, of Dana-Farber and
Brigham and Women's Hospital.
Carriers of the Lynch syndrome gene mutations have an 80 percent risk
of colorectal cancer beginning at a young age, as well as an array of
other cancers of the digestive system, brain and skin, and endometrium
and ovaries in women.
Syngal, director of gastroenterology at Dana-Farber/Brigham and
Women's Cancer Center, is the report's senior author along with Stephen
B. Gruber, MD, PhD, MPH, associate director for cancer prevention and
control at the University of Michigan Comprehensive Cancer Center.
Fay Kastrinos, MD, MPH, first author of the publication, noted,
"Patients with Lynch syndrome are living longer because we're doing a
better job with colonoscopic screening and using genetic testing as a
strategy for the prevention of colon cancer."
In light of the new findings, she said, "Lynch syndrome families with
pancreatic cancer should be included in ongoing studies to test the
effectiveness of screening modalities for pancreatic cancer."
Kastrinos's research was carried out while at Brigham and Women's
Hospital; she is currently at the Herbert Irving Comprehensive Cancer
Center at New York City's Columbia University Medical Center and directs
the hereditary colorectal cancer center.
is the fourth leading cause of cancer deaths in the United States,
according to the American Cancer Society, which projects 42,470 cases
diagnosed in 2009, and 35,240 deaths.
While colorectal cancer is increasingly being detected early and
prevented through colonoscopies and removal of precancerous polyps,
there is currently no effective means of early diagnosis for pancreatic
Scientists are testing imaging techniques such as endoscopic
ultrasound, CT and MRI scanning in an effort to detect small, treatable
tumors, but to date there is no evidence of a survival benefit.
Investigators are also searching for biomarkers that might signal the
early stages of the disease.
Mutations in several "mismatch repair" genes that fix copying errors
in DNA underlie Lynch syndrome. The researchers designed the study to
estimate the risk of pancreatic cancer in families with these inherited
mutations. A total of 147 families were drawn from colorectal cancer
registries at Dana-Farber and the University of Michigan Comprehensive
"Because pancreatic cancer is a relatively rare cancer, pooling
together the databases at the University of Michigan and Dana-Farber was
critical to this analysis," commented first co-author Bhramar
Mukherjee, PhD, a biostatistician at the University of Michigan School
of Public Health.
"Genetic counseling clinics tend to see more patients from families
with multiple cancers, which means risk estimates obtained by a naïve
statistical method are often highly inflated," said Mukherjee. "We used
appropriate methods to adjust for this bias to provide families with
more realistic risk estimates of pancreatic cancer."
The analysis revealed a nine-fold increase in risk of the disease
compared with the general population, and the cancer tended to appear
earlier. The absolute risk of pancreatic cancer in the Lynch families
was 1.31 percent at age 50 and 3.68 percent at 70 years. In the general
population, there is only a 0.04 percent risk at 50 years and a 0.52
percent risk at age 70.
Syngal, who is also an associate professor of medicine at Harvard
Medical School, noted that pancreatic cancers appear to "cluster" in
some Lynch syndrome families, while others don't have an increased
incidence of the disease. For that reason, she said, screening is
recommended only for patients carrying the Lynch mutations who also have
a family history of pancreatic cancer.
The research was funded by the National Cancer Institute and private
supporters. The study's other authors are Nabihah Tayob, MS, Victoria
M. Raymond, MS, and Fei Wang, MS, University of Michigan School of
Public Health, Ann Arbor; and Jennifer Sparr, MD, Prathap Bandipalliam,
MD, Elena M. Stoffel, MD, MPH, Dana-Farber.
Dana-Farber Cancer Institute (www.dana-farber.org)
is a principal teaching affiliate of the Harvard Medical School and is
among the leading cancer research and care centers in the United States.
It is a founding member of the Dana-Farber/Harvard Cancer Center
(DF/HCC), designated a comprehensive cancer center by the National
Cancer Institute. It is the top ranked cancer center in New England,
according to U.S. News & World Report, and one of the
largest recipients among independent hospitals of National Cancer
Institute and National Institutes of Health grant funding.
The mission of the U-M Comprehensive Cancer Center is the conquest of
cancer through innovation and collaboration. One of 41 centers to
receive the National Cancer Institute's "comprehensive" designation, the
center provides its patients diagnostic, treatment, and support
services in a collaborative environment, focused on excellence in
patient care. Drawing on the strengths of the University of Michigan
faculty, the Cancer Center has assembled a team of specialists who are
leaders in their fields to unravel the threat of cancer and to provide
care and comfort to those it affects. For information, visit www.mcancer.org.