Looking for early warning signs of pancreatic cancer

Pancreatic cancer is a nasty, stubborn killer that has thus far defied medicine’s best efforts at early diagnosis and curative treatment. In November, it claimed the life of my friend Peter Zimroth, a 78-year-old New York City attorney who was devoted to public service and who most recently oversaw the decline in the Police Department’s stop-and-frisk strategy.

Zimroth had been on my “most admired” list even before he married esteemed actress Estelle Parsons, who was 16 years his senior. Even during his yearlong, albeit losing, fight against cancer during the pandemic, Zimroth remained devoted to the public good, designing a brightly coloured T-shirt and cap bearing an urgent plea, “Smash the Virus! Get the Shot,” and raising more than $73,000 to support research at Memorial Sloan Kettering Cancer Center, where doctors tried valiantly to buy him more time.

Zimroth was fit and active and in otherwise good health before symptoms developed — in his case, stomach pains and constipation. By that time, the cancer had spread and it was too late to operate. His death follows that of several other well-known people who have succumbed to the same disease: Supreme Court Justice Ruth Bader Ginsburg, US Rep John Lewis, “Jeopardy!” host Alex Trebek and Apple co-founder Steve Jobs.

Although pancreatic cancer is a relatively rare cancer, it is so deadly that it is now on track to become the country’s second leading cause of cancer-related deaths by 2040. Currently, it accounts for about 3% of all cancers and 7% of cancer deaths. Overall, only 1 in 10 people diagnosed with pancreatic cancer survives five years. A cure is almost always a lucky accident, when the cancer is detected at an early, symptom-free stage during an unrelated abdominal scan or surgery and the tumour can be surgically removed.

Dr Brian Wolpin, director of the gastrointestinal cancer centre at the Dana-Farber Cancer Institute in Boston, told me that this is such a hard cancer to find early because “it’s relatively uncommon in the population and the symptoms it causes, like weight loss, fatigue and abdominal discomfort, are nonspecific and more likely due to other conditions.” As a result, he said, “when 80% of patients walk through my door for the first time, I know that we are highly unlikely to cure their cancer.”

RISK FACTORS FOR PANCREATIC CANCER

Still, there are several major risk factors for developing pancreatic cancer. Smoking doubles the risk and accounts for about one-quarter of all cases. Being obese, gaining excess weight as an adult and carrying extra weight around the waist, even if not otherwise very overweight, also increase one’s risk.

That may be why Type 2 diabetes, which is most often related to being overweight, is an important risk factor as well. Other risks include chronic pancreatitis, a persistent inflammation of the pancreas often linked to heavy alcohol consumption and smoking, and workplace exposure to certain chemicals, including those used in dry cleaning and metal work industries.

Older age is also a risk factor — about two-thirds of cases occur in those 65 and older. And family history may also play a role, including inherited genetic conditions such as mutations in the BRCA1 or BRCA2 genes that are most often associated with breast and ovarian cancers.

DIABETES AS AN EARLY WARNING SIGN

It has long been known that the best chance of surviving most cancers results from early detection, when the malignancy is totally confined to the organ or tissue in which it originates. (Blood cancers present different issues.) The pancreas is a rather small, carrot-shaped organ — about 6 inches long and less than 2 inches wide — that lies well hidden between the ribs and the stomach.

An early cancer in the pancreas doesn’t produce a lesion that can be felt, and it rarely causes symptoms that might prompt a definitive medical workup until it has escaped the confines of the pancreas and spread elsewhere.

But scientists are studying one possible early warning sign: a link between pancreatic cancer and newly developed Type 2 diabetes. Diabetes, too, arises in the pancreas, which contains specialised cells that produce the hormone insulin that regulates blood-sugar levels. And although it’s not yet known which comes first, diabetes or cancer, some research suggests that the recent development of Type 2 diabetes may herald the existence of cancer hidden in this organ.

An early study from 2005 of 2,122 residents of Rochester, Minnesota, by Dr Suresh Chari, now a gastroenterologist at the University of Texas MD Anderson Cancer Center, found that within three years of receiving a diagnosis of diabetes, people were six to eight times more likely than the general population to have pancreatic cancer. He, along with colleagues at the Mayo Clinic, also identified a gene called UCP-1 that may predict the development of this cancer in people with diabetes.

More recently, Dr Maxim Petrov, a professor of pancreatology at the University of Auckland School of Medicine, led a September 2020 study in New Zealand of nearly 140,000 people with Type 2 diabetes or pancreatitis, or both, who were followed for up to 18 years. The findings revealed that those who developed diabetes after an attack of pancreatitis were seven times more likely to get pancreatic cancer than others with Type 2 diabetes.

In 2018, the National Cancer Institute launched a study that is in the process of enrolling 10,000 people ages 50-85 with newly diagnosed diabetes or elevated blood-sugar levels. Participants will donate blood and tissue samples, and researchers will follow them in the hopes of identifying clues to early detection among those who develop pancreatic cancer.

Another effort begun last summer by the Pancreatic Cancer Action Network, called the Early Detection Initiative for Pancreatic Cancer, will enrol more than 12,000 participants with elevated blood-sugar levels and new-onset diabetes. Half will have periodic blood tests and undergo abdominal imaging based on their age, body weight and blood-glucose levels to look for evidence of early pancreatic cancer, while the others will serve as controls.

The goal of such studies is to identify biological markers, such as certain genes or proteins excreted by the tumour, that could be used in screening tests to indicate the presence of cancer when it could still potentially benefit from surgery. Alas, the results are not likely to be known before 2030, if then.

Meanwhile, Wolpin said doctors should consider “a checklist” of warning signs that might alert them to the presence of an early, curable cancer. Among things to consider, he said, are whether a patient’s glucose level is rising rapidly and is difficult to control with diabetes medication; whether patients with diabetes are losing weight with no explanation like a change in diet or exercise; or if patients have been fine for years and then suddenly in their early 70s get diabetes and it’s not clear why.

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