Obesity, lack of exercise and pancreatic cancer

The Association of Obesity and Lack of Exercise with the Risk of Pancreatic Cancer May be Mediated by a Protein in the Blood

August 15, 2007

Field(s) of Research: Prevention Research

PHILADELPHIA - Obesity and aversion to exercise have become hallmarks of modern society - and a new study suggests that a blood protein linked to these lifestyle factors may be an indicator for an increased risk of developing pancreatic cancer. Researchers from the Dana Farber Cancer Institute report their findings in the August 15 issue of Cancer Research, a journal of the American Association for Cancer Research.

In a study of 144 patients with pancreatic cancer and 429 people without the disease, a subset of patients with low blood levels of a protein called IGFBP-1 were at approximately twice the risk of developing pancreatic cancer. Low blood levels of this protein have previously been linked to excess weight and lack of physical activity. Their data originated from tens of thousands of men and women enrolled in four large-scale cohort studies - the Health Professionals Follow-Up Study, the Nurses' Health Study, the Physicians' Health Study and the Women's Health Initiative Observational Study - all of which followed the health of participants over numerous years.

"The prognosis for many patients with pancreatic cancer remains poor, so it is vitally important that we indentify and better understand risk factors for the disease, particularly risk factors that are modifiable" said lead study author, Brian M. Wolpin, M.D., attending physician at Dana Farber Cancer Institute. "In addition to cigarette smoking, exercise and weight control appear to be important modifiable risk factors for this difficult disease."

Pancreatic cancer is one of the leading causes of cancer death in America - over 33,000 Americans will likely die from the disease in 2007, according to projections from the American Cancer Society. Studies indicate that smoking is responsible for about 25 percent of pancreatic cancer cases, and obesity and lack of exercise may account for a similar amount, Dr. Wolpin said.

According to Dr. Wolpin, previous research has linked IGFBP-1 (insulin-like growth factor binding protein one) with increased risk of colorectal and endometrial cancer. Like its name suggests, IGFBP-1 is a molecule that binds with insulin-like growth factor (IGF), a hormone normally associated with growth and development. In the laboratory, IGF has been noted to increase the growth of pancreatic cancer cells. Since one role of IGFBP-1 is to sequester IGF, Dr. Wolpin and his colleagues were interested as to whether people who developed pancreatic cancer had lower blood levels of the IGFBP-1 protein.

To study the relationship between IGFBP-1 and pancreatic cancer, Dr. Wolpin and his colleagues chose pancreatic cancer patients enrolled in one of the four cohort studies and with blood drawn four or more years before developing cancer. The blood levels of IGFBP-1 from these patients were compared to those taken from 429 cancer-free people also enrolled in one of the cohort studies. According to their findings, patients with low blood levels of IGFBP-1 were nearly twice as likely to develop pancreatic cancer.

"We still have much to learn about the mechanisms by which obesity and sedentary lifestyle may contribute to the risk of pancreatic cancer," Dr. Wolpin said. "While it is too early to discuss IGFBP-1 as a suitable blood marker for pancreatic cancer, it is never too early to address the lifestyle issues that may contribute to low levels of IGFBP-1 and to an elevated risk of this difficult disease."

The study was supported by The Lustgarten Foundation for Pancreatic Cancer Research and the National Cancer Institute.