How to Minimize Pancreatic Cancer Risk

As an avid reader of obituaries, I’ve been struck by how many people these days are succumbing to pancreatic cancer, a cancer long considered rare.

And relatively speaking, it is still rare, accounting for just 3 percent of all cancers. But it is also one of the deadliest because symptoms almost never develop until the disease is advanced and incurable.

Although 55,440 cases, affecting 29,200 men and 26,240 women, are expected to be diagnosed this year in the United States, 44,330 people will die of it, often within months of diagnosis, making it the fourth leading cause of cancer deaths in this country (after lung, colorectal and breast cancer). Furthermore, it is on track to become the second most deadly cancer by 2030.

At the same time, cases of pancreatic cancer are rising, even though the leading known risk factor — cigarette smoking — has been declining for decades. That fact alone has prompted researchers to seek explanations for other causes and, it is hoped, find ways, in addition to quitting smoking, to prevent it and detect it while still curable.

In most of the approximately 6 percent of five-year survivors, pancreatic cancer is discovered early quite by accident, usually during a scan or surgery for some other reason. For example, in 2009, Ruth Bader Ginsburg, the associate justice of the Supreme Court, had part of her pancreas removed after a routine CT scan revealed a one-centimeter lesion. While that lesion was benign, a smaller tumor the surgeon found was malignant and had not yet spread beyond the pancreas.

The pancreas is a small two-part glandular organ — about 7 inches long and 1.5 inches wide — lying in the upper abdomen behind the stomach. It performs two vital functions. One part of the gland is a source of digestive enzymes and the other part produces the hormones insulin and glucagon that control blood levels of glucose and fatty acids.

Some known risk factors for pancreatic cancer are beyond an individual’s control: older age, being an African-American or Ashkenazi Jew and having two or more first-degree relatives (parents or siblings) who have had the cancer.

But it is the modifiable risk factors that are currently of greatest concern. Aside from tobacco smoking, which accounts for 20 percent to 25 percent of pancreatic cancers even as this risk factor continues to decline, the main risks for pancreatic cancer cases and deaths are obesity, Type 2 diabetes and metabolic syndrome, all of which have risen to epidemic levels in recent years.

Data gathered in many studies “clearly show a relationship to obesity,” said Donghui Li, a molecular epidemiologist at the M.D. Anderson Cancer Center in Houston. “The higher the B.M.I., the greater the risk of pancreatic cancer,” she said in an interview. “Obesity contributes to both onset and progression of this cancer.”

Dr. Li added, “The distribution of fat also plays a role — the higher the waist to hip ratio, the greater the risk.” She found that cancer risk was greater the earlier in life a person becomes obese, and survival time was shorter among those who were still obese when the cancer was diagnosed.

Obesity is also the leading risk factor for the development of Type 2 diabetes, in which the body resists the action of insulin, prompting the pancreas to produce more and more of this hormone. Insulin promotes cell growth, providing a link between diabetes and the development of pancreatic cancer.

However, the relationship is complicated, to say the least. In a 2011 report in Molecular Carcinogenesis, Dr. Li noted that “diabetes or impaired glucose tolerance is present in 50 to 80 percent of patients with pancreatic cancer.” She said, “Diabetes is both a cause and consequence of cancer,” although which comes first — diabetes or cancer in the organ that controls blood glucose — is not crystal clear.

A European study of more than 800,000 people with Type 2 diabetes found this disease is sometimes an early sign of an otherwise hidden pancreatic cancer.

In studies at the Mayo Clinic, elevated glucose levels, a condition called pre-diabetes, were detected in some patients two years before pancreatic cancer was diagnosed. In these patients, Dr. Li explained, diabetes is actually a symptom of the hidden cancer. It is a type of diabetes called 3C, caused by a diseased or damaged pancreas, and medical researchers are now looking for ways for doctors to readily distinguish between Type 3C and Type 2 diabetes.

The lag time between the development of diabetes and diagnosis of cancer is a potential window of opportunity that may enable cancer detection at an early, curable stage, Dr. Li said.

If a biomarker for the cancer was identified, it may be possible to find cancer in these patients when the tumor is too small to be seen on a scan and before symptoms develop. For example, an antibody might be used that targets a molecule on small tumors.

Dr. Li urged doctors to be alert to the possibility of hidden cancer in patients newly diagnosed with diabetes who are 50 or older, have no family history of the disease, are losing weight and their diabetes is not controlled by oral medication.

In general, when diabetes or pre-diabetes is present for many years before pancreatic cancer is found, the blood sugar abnormality is likely to have played a role in initiating or promoting the growth of cancer. The longer patients have diabetes, the lower the cancer risk, though even after 15 years with the disease the risk of pancreatic cancer is higher than in people without diabetes.

In the less than 10 percent of people with familial pancreatic cancer, many of whom are in a national tumor registry at Johns Hopkins Medical Center, genetic testing has identified several genes associated with the cancer that could predict their cancer risk. The higher the risk, the more frequently a CT scan could be done to look for a relatively early cancer.

Early diagnosis is vital, Dr. Li said, because pancreatic cancer is highly resistant to most therapies and often recurs after surgery. Currently, only 20 percent of cancers are even eligible for surgery, she said. The pancreas is next to very large blood vessels and when the tumor involves them, it cannot safely be removed.

One bright spot for people with diabetes: The drug metformin, often used by patients to help control blood sugar, has in some studies been associated with a reduced risk of pancreatic cancer and improved survival chances for those who develop the cancer. This drug, which has also been linked to longevity and healthy aging, is an inexpensive generic with an excellent safety record.