Please could you explain what antioxidants are and where they are found?
The antioxidants that we mainly looked at were selenium, vitamin C and vitamin E. They are chemicals which inactivate pro-oxidants or free radicals. Smoking and normal metabolism can lead to the production of free radicals.Free radicals are toxic on cells and they may induce cancer. Antioxidants are essentially chemicals that can inactivate or nullify these pro-oxidants.
Vitamin C is found mainly in citrus fruits. Vitamin E is found in vegetables oils; nuts; seeds; egg yolks and so forth. The level of selenium in food depends on the selenium content of the soil. It can be found in cereals, nuts and fish. Thus antioxidants have many different sources.
Please could you give us a brief introduction to pancreatic cancer?
In the world there are around a quarter of a million cases of pancreatic cancer each year. Unfortunately, the number of people being diagnosed with pancreatic cancer is going up.It is a cancer which generally presents its symptoms when it is at an advanced stage. The pancreas is deep within the abdomen. The cancer often has to have spread to the liver, the lungs or other places before it displays any symptoms.
Once the diagnosis has been made then unfortunately the prognosis and outlook is very poor. It has the worst outlook of any cancer, predominantly because it presents at such an advanced stage. Most patients survive about 5 months after they have been diagnosed with pancreatic cancer.
About 1 in 10 patients are suitable to have surgery, but it is major surgery. Of the 90% left, about half may be suitable for chemotherapy. This is still very toxic and it only increases patient’s survival by about several months. For the other 50% of people, palliative care is the focus. This involves relieving pain, jaundice and any other symptoms.
Unfortunately, it is a cancer with a very bad prognosis and there are very rarely any cures available. Hence, in our work we are looking at it from the other direction. We are focussing on what may be the causes of pancreatic cancer to see if people could alter their lifestyle in order to reduce their risk.
What causes pancreatic cancer?
The complete causes of pancreatic cancer are not known. Probably about a quarter of cases are caused by cigarette smoking. Carcinogens in cigarette smoke can get to the pancreas and induce cancer.Generally it is known that smoking is bad for heart disease, lung cancer and so forth; but very few people know that it is one of the causes of pancreatic cancer. Smoking is a definite cause of pancreatic cancer, but it is probably only responsible for a quarter of cases.
We know that people with type 2 diabetes, which tends to present in later life, are associated with an increased risk of pancreatic cancer. Nobody knows for sure why that happens but it may be as a result of the metabolic consequences of diabetes which are toxic on the pancreas.
There is emerging, but not complete, evidence that the rise in obesity in the western world may be important as well. Possibly by inducing generalised body chemical changes which may be toxic on the pancreas.
Roughly about two thirds of cases we don’t really know what the cause is, hence why we are looking at diet to see if different aspects may be involved. This is the first study in the series where we have looked at the potential protective features of antioxidants.
In the future we will look at other nutrients which may possibly be causative or protective. This is an on-going work to try to build up a complete picture of what the causes may be.
How significant was the intake of dietary antioxidants on the risk of pancreatic cancer?
We found a threshold effect of the more antioxidants people ate above a certain level the lower their risk. This meant that once you got to a particular level of consumption, it didn’t really matter how many more you ate. It seemed to be the people at very low intakes who were at increased risk of pancreatic cancer.If you divided people into quarters across the population: the risk of the people in the top three quarters – 25%-100% intake – was, in all the antioxidants, about 2/3rd’s lower than those who didn’t.
Specifically for selenium, the people, who ate the top amounts, in the top three quarters’ risk was about half that of people who didn’t.
What seems to be important is that it is bad if you consume very low amounts of antioxidants. Once you eat more, your risk levels off. There is a very big inverse association with risk of pancreatic cancer at very low intakes of antioxidants.
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Sally Ride and a Primer on Pancreatic Cancer
I was in medical school when Sally Ride, Ph.D, rode in space. Yesterday, I learned that she died of pancreatic cancer at the ripe age of 61 years. According to multiple reports, the physicist-astronaut had faced the disease for 17 months. She was a remarkable woman. Her case of pancreatic cancer was, unfortunately, typical in its course.Pancreatic cancer is one of the few tumors with a rising incidence in North America, according to the American Cancer Society's (ACS) 2012 report. The most common form of the disease, called adenocarcinoma, arises from glandular cells in the main part of the pancreas. Nearly 44,000 people will receive a diagnosis this year, and over 37,000 will die from it. Pancreatic cancer ranks fourth among malignant killers in the U.S.
Scientific understanding of this tumor type lags, although several recent studies offer insights in its genetic underpinnings. A 2008 review attributes between 5 and 10 percent of cases to an inherited mutation or familial disposition. In most other affected individuals, pathologists find multiple acquired genetic aberrations in the cancer cells.
A recent publication in the ACS journal Cancer indicates that the rising incidence of pancreatic cancer -- on the order of 1 percent per year between 1999 and 2008 -- is mainly affecting Caucasian men and women. The only established risks are smoking tobacco and obesity; the cause for the increase is unknown. The statistics are bleak: In the latest ACS analysis, five-year survival was poor, in the range of five percent and, surprisingly, independent of the tumor stage at diagnosis; survival in the United States did not improve in the decade leading up to 2008.
Years ago, the only treatments for pancreatic cancer were surgery, to remove the tumor, and radiation. Surgery to the pancreas can be risky, especially in older patients. The digestive enzyme-containing organ is centrally located, near large vessels and easily inflamed. What's more, procedures like a Whipple -- in which all or part of the pancreas is removed -- are rarely curative. The problem, more often than not, is that by the time a person with pancreatic cancer or their doctor notices something's wrong, the tumor's already invaded nearby structures like the bile duct where it can cause obstruction, jaundice, and pain.
After surgery, some patients opt for an observational or palliative care approach. Treatments for pancreatic cancer after surgery include radiation and sometimes chemotherapy, typically with 5-fluorouracil (5-FU) and, in recent years, gemcitabine (Gemzar). So far the FDA has approved one targeted therapy, erlotinib (Tarceva) for treatment, in combination with chemotherapy, of advanced pancreatic tumors. This pill is an enzyme inhibitor; it blocks activity of the Epidermal Growth Factor Receptor (EGFR) and likely other signaling molecules aberrantly "turned on" in malignant cells. Like other drugs of its type, Tarceva is costly -- to the tune of $30,000 per year, and can be toxic.
Scientists have observed that a particular oncogene, a DNA element that turns cells cancerous, is activated in a high fraction of pancreatic tumors. The K-ras oncogene may prove a useful target for future therapies, but so far none are established. Pancreatic cancer was also notably one of the first tumor types for which therapeutic vaccines were tested. Trials are ongoing to see if immunization strategies may help patients with various stages of this disease.
Sally Ride's unusual career reflected progress in science, technology and, also, attitudes toward women. She was smart and not particularly risk-averse. She took a ride into space and she did so knowing the potential harms and benefits in her journey, an ambitious experiment of sorts. She set a lead with forward-but-responsible, grounded thinking of the sort that patients, doctors and researchers in oncology might follow, today.
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