People with a family history of pancreas cancer now
have a way to accurately predict their chance of carrying a
gene for hereditary pancreas cancer and their lifetime risk
of developing the disease. Developed by Johns
Hopkins Kimmel Cancer Center researchers, the novel
computer software tool is designed to help genetic
counselors and physicians decide who would most benefit
from early screening.
An estimated 10 percent of aggressive and highly fatal
cases of the disease are caused by inherited genes. "Even
if there is a 100 percent chance that an individual carries
a pancreas cancer gene, their risk for developing the
disease is only 20 [percent] to 25 percent over their
lifetime," said Alison Klein, assistant professor and
director of the National Familial Pancreas Tumor Registry
at Johns Hopkins. "So, while it's a rare disease, the need
for screening in these persons is important."
The risk "calculator," based on similar tools for
breast and colon cancer, estimates a percentage score of
probability that a person carries a pancreas cancer gene.
Called PancPRO, it also computes an individual's lifetime
risk of developing the disease.
Although researchers have not yet identified specific
genes that cause pancreas cancer, they can estimate high
risk based on clusters of family members with a history of
the disease. "We know how genes behave, and coupled with
information about a family — who has the disease,
their age, family size and causes of death — our
model can provide a good estimate of an individual's risk,"
Early risk assessment has long been sought for
pancreas cancer that runs in families, Klein says, because
of the difficulty that doctors have diagnosing the disease
before it has spread. Survival rates are extremely low.
Each year in the United States, pancreas cancer
strikes more than 37,000 people and kills about the same
number. Most patients succumb to the disease within six
months of being diagnosed. The five-year survival rate is 5
To test the model's effectiveness for predicting
cancer, Klein and her colleagues fed the software family
history information given by more than 6,000 individuals in
961 families when they joined the Johns Hopkins pancreas
cancer registry several years ago. Klein's team divided
registrants into groups representing the number of pancreas
cancer patients in each family, from one to three or more
members, and compared predictions from the PancPRO model
with what actually occurred in these families from one to
11 years later. On average, the model calculated higher
risk scores for individuals who developed pancreatic cancer
than for those who remained disease free.
Current practices for identifying pancreatic cancer
risk without the new model are slightly better than a coin
toss at 61 percent, but PancPRO correctly assesses risk 75
percent of the time, taking into account all potential
threshold values for defining risk. Overall, 26 individuals
developed cancer, and PancPRO predicted slightly more at
The researchers' published results appear in the April
10 issue of the Journal of Clinical Oncology.
Studies are under way to determine the effectiveness
of screening, based on risk assessment, which includes an
ultrasound procedure conducted through an endoscope
inserted through the mouth, esophagus and stomach to detect
precancerous changes. The test provides sound-wave pictures
of the pancreas, which sits next to the stomach.
Klein says that the new model also needs to be
assessed in other populations besides the Johns Hopkins
registry, and she hopes to determine how insurers would pay
for screening procedures. Her group also will be studying
whether PancPRO is more effective in selecting candidates
for screening than current criteria based only on the
number of family members with the disease.
The authors caution that results from PancPRO should
be interpreted only by a genetic counselor and a physician.
The model is freely available to health care professionals
files/65844.html and at
Persons with a family history of pancreas cancer who
wish to seek advice on their risk can contact a genetic
counselor through the National Society if Genetic
Counselors' Web site at
Funding for the study was provided by the National
Cancer Institute's Specialized Programs of Research
Excellence and the Michael Rolfe Foundation.
Co-authors are Wenyi Wang, Sining Chen, Kieran A
Brune, Ralph H. Hruban and Giovanni Parmigiani, all of