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Research Findings Reveal Some of Pancreatic Cancer's Mysteries

Network - Fall 2009

By Bayan Raji

Most people know little about the pancreas and its functions. Yet, the oblong
organ — about six inches in length and located behind the lower portion of the stomach — plays an important role. Not only does it produce insulin and other hormones that help the body absorb sugar, but it also produces juices that aid in digestion.

People with pancreatic cancer exhibit few, if any, signs or symptoms of the disease in the early stages when it would be most treatable. The fact that it can spread rapidly and is generally diagnosed after it has metastasized makes it the fourth leading cause of cancer death in men and women in the United States.

However, research in the field is ongoing with several new discoveries by
M. D. Anderson researchers. Each advance brings them closer to determining who is at risk of the disease and to finding a cure.

Clues in our DNA

In one study, researchers discovered that abnormalities in our genes that repair mistakes in DNA replication may identify people who are at risk of developing pancreatic cancer.

The results, published in the Jan. 15, 2009, issue of Clinical Cancer Research, came after researchers studied a control group of 734 patients with pancreatic cancer and 780 healthy individuals.

Donghui Li, Ph.D.

The M. D. Anderson team found that the risk of developing pancreatic cancer was 77% lower among individuals with the variant form of the LIG3 gene (LIG3 G-39A AA). In contrast, people who carried the variant form of the ATM gene (ATM D1853N AA) were more than twice as likely to develop the disease as those without the genetic variation.

Donghui Li, Ph.D., professor in the Department of Gastrointestinal Medical Oncology at M. D. Anderson and lead author on the study, says the goal of this research was to identify high-risk patients — like diabetics or heavy smokers — and to do follow-up work.

“We need to develop biomarkers that will enable us to do a quick genetic test on a diabetic patient, heavy smoker or someone with a family history of pancreatic cancer,” Li says. “We could then do a screening test, identify those with the highest risk and monitor them more closely.”

Weight plays a significant role

A study published in the June 24, 2009, issue of the Journal of the American Medical Association indicates a strong relationship between high body mass index in young adulthood and developing pancreatic cancer at an earlier age. Li, the study’s senior author, says 25% of pancreatic cancer cases are associated with obesity.

While most studies focus on the effect of high BMI in adulthood, researchers at
M. D. Anderson participated in the first study to explore the relationship between high BMI and risk of pancreatic cancer throughout a lifetime.

For example, individuals overweight from 14 to 19 years old and/or in their 30s had a 60% increased risk of the disease. Those who were obese from their 20s to their 40s were found to have a 2-3 times higher risk of developing pancreatic cancer. The risk of developing the disease appeared to level off for those who gained excess weight in their 40s and was not statistically significant after age 50.

“This is the first study to explore at which ages excess body weight predisposes an individual to pancreatic cancer,” Li says. “With our epidemiological research, we aimed to demonstrate the relationship between BMI and risk of pancreatic cancer across a patient’s life span. We also wanted to determine if there was a time period that specifically predisposes someone to the disease, as well as find the links between BMI and cancer occurrence and overall survival of the disease.”

Diabetes medication reduces risk

A handmade model of insulin

Metformin, the most commonly prescribed medication for type 2 diabetes, was found to reduce the risk of pancreatic cancer by 62% compared to those who never took the drug, according to
M. D. Anderson researchers. The results were published in the
Aug. 1, 2009, issue of Gastroenterology.

“This is the first epidemiologic study of metformin in the cancer population, and it offers an exciting direction for future chemoprevention research for a disease greatly in need of both treatment and prevention strategies,” Li says.

For the case control study, the researchers enrolled 1,838 participants — 973 patients with pancreatic adenocarcinoma treated at M. D. Anderson between 2004 and 2008 and 863 cancer-free individuals (controls), all companions of
M. D. Anderson patients.

Of the participants, 259 patients and 109 controls were diabetics. The groups were matched by age, race and sex. Personal interviews were conducted to collect such information as smoking history, family history of cancer, alcohol use and body mass index throughout their lives. Diabetics also were asked about their anti-diabetic medications and the length of time they had taken them.

Diabetics who took metformin alone or with other diabetic therapies had a 62% reduction in risk of developing pancreatic cancer, compared to those who never used the drug. Other diabetes-associated risk factors, such as history of smoking, being overweight or obese, and glycemic control, did not have significant effects on the relationship between metformin use and pancreatic cancer risk.

Li says the metformin study is not without limitations, including the relatively small size of the study’s diabetic population, but hopes the research will be replicated in a larger sample size. Still, the findings present the immediate opportunity to explore metformin as a chemopreventive agent.

© 2015 The University of Texas MD Anderson Cancer Center