Possible Genetic Link to Pancreatic Cancer
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Mayo Clinic researchers have found the risk of developing pancreatic cancer at a young age (under 60) to be twice as high for people who carry a mutation of the gene that causes cystic fibrosis, compared to noncarriers. Results of a pilot and follow-up study were reported Oct. 14, 2005, online in the journal Gut.
Pancreatic cancer kills over 32,000 people in the United States each year Twenty percent are under age 60. “Being able to screen for a genetic mutation that points to a higher risk will enable us to intervene earlier,” says Robert McWilliams, M.D., Mayo Clinic oncologist and lead author of the study. “Early screening is one step in the process to developing ways to prevent or cure this deadly disease.”
Nearly all patients who develop pancreatic cancer will succumb to the disease. A genetic marker that helps physicians find individuals most at risk to develop the cancer also will help find it early enough to perform effective surgery.
Individuals who carry the cystic fibrosis gene mutation are at increased risk for pancreatitis — inflammation of the pancreas. Chronic pancreatitis has been proven to increase the risk of pancreatic cancer 26-fold, which led Mayo Clinic researchers to the hypothesis that mutations in the gene that carries cystic fibrosis may be directly linked to a higher risk for pancreatic cancer.
From October 2000 to April 2004, pancreatic cancer patients seen at Mayo Clinic were recruited for the study — 75 percent of all new patients registered. The pilot study reviewed 33 patients from 41 to 81 years old, with seven having a diagnosis of pancreatitis at least one year prior to cancer diagnosis. Of the 33, a mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in two patients, both younger than 60. A follow-up study was designed to test all the young-onset cases in the registry, resulting in a study group of 166 young-onset pancreatic cancer patients. This study showed that mutations in the CFTR gene were present in twice as many young pancreatic cancer patients than in the comparison group, which consisted of all patients tested for CFTR at Mayo Clinic from November 2003 to May 2004.
Causes, incidence, and risk factors
Pancreatic cancer is the 4th leading cause of death from cancer in the U.S. The disease is slightly more common in men than in women, and risk increases with age.
The cause is unknown, but it is more common in smokers and in obese individuals. Almost 1/3 of cases of pancreatic carcinoma can be attributed to cigarette smoking. There is controversy as to whether type 2 diabetes is a risk factor for pancreatic cancer. A minority of cases are known to be related to hereditary syndromes.
Further study is needed, and Dr. McWilliams cautions that the overall risk to carriers of cystic fibrosis is still small. However, he and his colleagues say this is a step towards greater understanding of who is at risk for developing pancreatic cancer at a young age. “We are excited about the finding,” says Dr. McWilliams, “And we have an additional study underway with more patients to confirm the finding for young patients as well as look at implications for those over age 60.”
Other Mayo Clinic researchers involved with this study include: W. Edward Highsmith Jr., Ph.D.; Kari Rabe; Mariza de Andrade, Ph.D.; Larry Tordsen; Leonard Holtegaard; and Gloria Petersen, Ph.D.
This research was conducted through a National Cancer Institute (NCI) SPORE grant — Specialized Programs of Research Excellence. As an NCI-designated Comprehensive Cancer Center, Mayo Clinic Cancer Center is nationally recognized for excellence in education, research and treatment of cancer. The NCI established the SPORE program in 1992 to promote interdisciplinary research and speed the transition of basic research findings from the laboratory to applied settings involving patients and populations. The program’s goal is to bring into clinical care novel ideas that have the potential to reduce cancer incidence and mortality, improve survival and enhance patients’ quality of life. Laboratory and clinical scientists work collaboratively to plan, design and implement research programs focused on cancer prevention and control, early detection, diagnosis, treatment and survival.
Revision date: July 8, 2011
Last revised: by Jorge P. Ribeiro, MD
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