Pancreatic Cancer Linked to Insulin Resistance in Male Smokers

A new study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, shows for the first time that male smokers with the highest insulin levels are twice as likely to develop pancreatic cancer as men with the lowest levels. Similarly, men with glucose levels in the range of clinical diabetes were twice as likely to develop the cancer as men with normal glucose levels. This study examined data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study* of 29,000 male smokers in Finland and appears in the December 14, 2005, issue of the Journal of the American Medical Association**.

Study investigators drew blood from enrollees when they joined the ATBC Study in the mid-1980s. This allowed the researchers to determine participants’ overnight fasting insulin and glucose levels many years ahead of when they might be diagnosed with cancer. Over the course of 17 years, 169 men in the study developed pancreatic cancer.

Study results show a two-fold increase in risk of pancreatic cancer in the quartile of men with the highest fasting serum insulin levels (greater than 6.1 microinternational units per milliliter) compared to those in the lowest quartile (less than 2.75 microinternational units per milliliter). Increasing concentrations of glucose, insulin, and insulin resistance were also associated with pancreatic cancer. Moreover, the risk for pancreatic cancer increased with longer follow-up time.

“Some men were in the highest quartile of insulin or had abnormal glucose levels more than a decade before the cancer appeared,” noted lead researcher Rachael Stolzenberg-Solomon, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics. “It is important to note, however, that this study was only done in male smokers and that any assumptions about risk in the general population or whether one can determine their own pancreatic cancer risk specifically based on insulin levels is premature.”

In their analysis, the researchers excluded men who developed pancreatic cancer within five years of having their blood drawn. This exclusion reduced the likelihood of including men whose elevated insulin levels may have been caused by undetected pancreatic tumors.

Smoking, aging, and perhaps obesity are the only known risk factors for pancreatic cancer, one of the most deadly cancers. Only 4 percent of people survive five years after being diagnosed with the disease. There are few treatments, and the cancer is frequently discovered only after a tumor has spread beyond the pancreas. It is estimated that 31,800 people in the United States — including 15,820 men — will die from pancreatic cancer in 2005.

Cancers of the colon, breast, liver, and pancreas are among those that tend to occur with type-2 diabetes among adults. Clinical diabetes is defined as glucose levels greater than or equal to 126 milligrams per deciliter. But epidemiologic studies on the subject are inconsistent, and researchers are only beginning to understand how the diseases might be related and how best to treat patients diagnosed with both type-2 diabetes and cancer. It is possible that type-2 diabetes could be related to pancreatic cancer through the growth regulatory effects of insulin. Few studies have been done specifically to understand how the diseases are related. Instead, researchers have focused largely on identifying cancers that occur with diabetes (or pre-diabetic states) and explaining why this happens.

This study supports the longstanding hypothesis that insulin is a growth promoter for pancreatic cancer. “This study of insulin levels gives us another important clue about the various influences that are probably important in the risk of developing pancreatic cancer, and possibly other cancers, particularly in smokers,” said Demetrius Albanes, M.D., senior researcher for the NCI team.

The findings must be replicated in other groups, including women and non-smokers, but the results are consistent with other recent studies.

An earlier study in JAMA*** found that diabetes and elevated fasting glucose levels were independent risk factors for several major cancers, including pancreatic cancer, among 1.3 million Koreans. The participants were far leaner than those in studies involving Westerners. Noting that obesity was not a factor in the results, the researchers suggested that elevated insulin levels may account for the increased cancer risk.

In May 2005, an analysis of 36 studies involving diabetes and pancreatic cancer found a modest causal association between type-2 diabetes and the cancer. After obesity and smoking, diabetes may be the third modifiable risk factor for pancreatic cancer, the researchers concluded in the British Journal of Cancer****.

From National Cancer Institute

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