As a physician, there is probably no single question I get more frequently than “What causes cancer – and how can I avoid getting it?”

We human beings always tend to look for that “one elusive thing” that will solve our problems. Even doctors do it. But the reality is that many things in life are made up of many small factors which combine in mysterious ways to produce big results. Cancer is one of those big things. There are many relatively small contributors that “cause” cancer and affect how it grows and spreads, and this complexity is why questions about cancer’s cause and cure are so difficult to answer.

In this blog we’ll focus on a few tips for cancer prevention. In upcoming blogs we’ll consider some supplements you should consider that we believe will help reduce your risk of getting cancer, and also suggest some things you can do if you already have cancer.

• It is generally an accepted fact that too much fat can contribute to causing cancer. This established fact is all too often ignored. Being overweight raises your risk of breast cancer, colon cancer and prostate cancer, three types of cancerous tumors that are fat-related.  No doubt there are several other cancers that are also probably related to weight.

• Doctors also understand that inflammation can contribute to causing cancer. We’re not exactly sure why this is so, but there are healthy ways to diminish and even prevent inflammation in muscles and joints and so reduce cancer risk. Consider these simple ideas:

• Reduce your intake of animal fats and replace them with healthy fats. Most animal fats have what’s called a saturated omega 6 structure, and when your body metabolizes these fats, inflammation results. Healthy omega 3 fats, from sources including fish, krill, many nuts such as almond and walnuts, and some grains like flax, all reduce inflammation.
• Moderate exercise decreases inflammation. Be careful, though: over-exercising actually produces inflammation. So exercise in moderation. Exercise is what doctors call “dose dependent”: do it, but don’t over-do it.
• Along with moderate exercise, muscle-development also reduces inflammation. When a muscle exercises it produces anti-inflammatory peptides: the more muscle you have, and the more regularly it gets used, the more anti-inflammatory peptides you produce.

Besides changing our fat consumption and reducing inflammation, here are two more things you can do to reduce your cancer risk:

• Most people know that too much sun can contribute to causing cancer. But you should know that moderate sun exposure, up to 20 minutes a day, may actually reduce cancer risk. (This may be related to Vitamin D which the body derives from sunlight.)

• On the positive side, you can reduce cancer risk by eating deeply pigments fruits, berries, and vegetables – the more, the better. Do your body a favor: add plenty of these cancer-fighting foods to your diet. They taste great, and they’ll help you stay healthier longer!

A recent open access paper from a Spanish research group outlines yet another methodology to add to the growing list of ways to increase healthy life span in mice. Progress is signified by diversity these days; there are, I think, more than twenty different demonstrated methods of bringing about meaningful extension of life in mice as of today.

RasGrf1 deficiency delays aging in mice:

We observed that mice deficient for RasGrf1-/- display an increase in average and most importantly, in maximal lifespan (20% higher than controls). This was not due to the role of Ras in cancer because tumor-free survival was also enhanced in these animals.

Aged RasGrf1-/- displayed better motor coordination than control mice. Protection against oxidative stress was similarly preserved in old RasGrf1-/-. IGF-I levels were lower in RasGrf1-/- than in controls. Furthermore, SIRT1 expression was increased in RasGrf1-/- animals. Consistent with this, the blood metabolomic profiles of RasGrf1-deficient mice resembled those observed in calorie-restricted animals.

…

Our observations link Ras signaling to lifespan and suggest that RasGrf1 is an evolutionary conserved gene which could be targeted for the development of therapies to delay age-related processes.

The results are similar to those noted for PAPP-A knockout mice – both longer lives and less cancer. At this stage it’s anyone’s guess as to whether many of these methodologies in fact operate through the same thicket of connections and mechanisms in mammalian biochemistry. Time, and further research, will tell.

RasGrf1 was mentioned here last year in connection with the intriguing bi-maternal mice:

mice artificially produced with two sets of female genomes have an increased average lifespan of 28%. Moreover, these animals exhibit a smaller body size, a trait also observed in several other long-lived mouse models. One hypothesis is that alterations in the expression of paternally methylated imprinted genes are responsible for the life-extension of bi-maternal mice. Considering the similarities in postnatal growth retardation between mice with mutations in the Rasgrf1 imprinted gene and bi-maternal mice, Rasgrf1 is the most likely culprit for the low body weight and extended lifespan of bi-maternal mice.

This latest work adds weight to the supposition quoted above.

The modest goals of the mainstream longevity science community are outlined by one of its members in this article – to enable everyone to age as slowly as only some people presently do. No radical life extension or rejuvenation, as would be enabled by the damage repair approach to longevity science, but rather just a gentle slowing of aging, enabled by technologies that would probably not emerge in time to benefit those of us in middle age today. “It is the aging of our cells that causes us to develop most diseases, says Dr. Nir Barzilai, professor of medicine and genetics at the Albert Einstein College of Medicine in New York. ‘We know this, paradoxically, because of the amazing success we have had in treating heart disease. We have been able to save people from heart attacks with stents and bypass surgery – only to find that within a year or two they develop Alzheimer’s, diabetes or cancer at an alarming rate. Why? Because we have never treated the underlying aging of their cells. We have simply treated the disease manifestation.’ So, explains Barzilai, if we can find the processes in the body that control aging and find a way to treat them, we will be able to protect people from the diseases of aging. Barzilai heads a unique longevity study of more than 500 people who have reached the age of 100. The LonGenity study is looking at the genetic makeup of centenarians to identify the biological markers that explain why they live so long and so well. Because the remarkable thing about these people is not simply that they live to the age of 100, it is that they live to 100 in pretty good health. Just why they live that long without getting sick and dying is what Barzilai wanted to find out.”

Link: http://www2.macleans.ca/2011/03/17/living-like-a-centenarian/

Via EurekAlert!: “A gene therapy called NLX-P101 dramatically reduces movement impairment in Parkinson’s patients, according to results of a Phase 2 study … The approach introduces a gene into the brain to normalize chemical signaling. … The study is the first successful randomized, double-blind clinical trial of a gene therapy for Parkinson’s or any neurologic disorder … Half of patients receiving gene therapy achieved dramatic symptom improvements, compared with just 14 percent in the control group. Overall, patients receiving gene therapy had a 23.1 percent improvement in motor score, compared to a 12.7 percent improvement in the control group. … Improved motor control was seen at one month and continued virtually unchanged throughout the six-month study period. … Gene therapy is the use of a gene to change the function of cells or organs to improve or prevent disease. To transfer genes into cells, an inert virus is used to deliver the gene into a target cell. In this case, the glutamic acid decarboxylase (GAD) gene was used because GAD makes a chemical called GABA, a major inhibitory neurotransmitter in the brain that helps ‘quiet’ excessive neuronal firing related to Parkinson’s disease. … In Parkinson’s disease, not only do patients lose many dopamine-producing brain cells, but they also develop substantial reductions in the activity and amount of GABA in their brains. This causes a dysfunction in brain circuitry responsible for coordinating movement.”

Link: http://www.eurekalert.org/pub_releases/2011-03/nyph-gtr031411.php

Researchers recently demonstrated that increased cellular housekeeping could slow neurodegeneration, and here a different group show the same outcome: “Cells, which employ a process called autophagy to clean up and reuse protein debris leftover from biological processes, were the original recyclers. A team of scientists [have] linked a molecule that stimulates autophagy with the reduction of one of Alzheimer’s disease’s major hallmarks, amyloid peptide. Their finding suggests a mechanism that could be used to eliminate built-up proteins in diseases such as Alzheimer’s, Down syndrome, Huntingdon’s and <a href="http://en.wikipedia.org/wiki/Beta_amylo&quot; the="The" molecule,="molecule," called="called" smer28,="SMER28," spurs="spurs" autophagy,="autophagy," which="which" in="in" turn="turn" eliminates="eliminates" unwanted="unwanted" materials="materials" such="such" as="as" amyloid-beta, the protein aggregates that cause Alzheimer’s plaques. Increasing autophagy, either through a drug or a natural process such as diet, could improve the outcome for people with neurodegenerative diseases … The researchers [tested] various compounds for their ability to reduce the buildup of amyloid-beta by exposing cultured cells to compounds known to activate autophagy. They then compared the effect of these compounds by removing growth factors from the culture medium, a well-established stimulant of autophagy known as ’starvation.’ The researchers found that SMER28 was the most effective compound, and focused their studies on it to characterize the cellular components involved in this phenomenon. They compared the effect of SMER28 on amyloid-beta formation using normal cells or cells where the expression of genes known to be involved in autophagy was reduced or abolished. They found that three important autophagic players were involved, and one of them was essential for SMER28’s effect.”

Link: http://www.eurekalert.org/pub_releases/2011-03/ru-mts031611.php

The present generation of therapies for rheumatoid arthritis are based on TNF inhibition – a fairly crude manipulation of the immune system when considered in the grand scheme of what is possible, but one that is getting better. From Technology Review: “A new protein engineered to inhibit molecules that cause inflammation not only reduces symptoms of rheumatoid arthritis in mice but also may have potential to reverse the disease’s course. Researchers hope the findings will point toward a new therapy for this crippling and difficult-to-treat disease, which occurs when the immune system attacks the body’s own joints. Even medications that are most successful in halting joint inflammation are effective in only about half of the patients who try them. … The new synthetic protein [appears] to target TNF in a far more specific fashion and could be produced at a small fraction of the cost [of present TNF inhibitors]. … a protein called progranulin binds to TNF receptors and that administering the protein to mice with rheumatoid arthritis reduced or even eliminated their symptoms. Then they determined which fragments of progranulin were responsible for binding to TNF and combined those fragments to engineer a protein that works even better to suppress disease. Mice with mild arthritis appeared to be disease-free after several weeks of regular injections of the modified progranulin.”

Link: http://technologyreview.com/biomedicine/35091/

The Global Forum for Longevity is an industry-sponsored forum taking place later this month; fairly mainstream, no talk of radical life extension or other forms of futurism that might lead to intellectual discomfort for some. I mention it because it is a symptom of the growing interest in biogerontology on the part of the vast insurance industries of the world – which should not be a surprising phenomenon. To find people likely to pay close attention to the future of longevity science, you want to look amongst the folk who stand to gain or lose a great deal of money due to changes in human life spans. Life insurance, pensions, and other forms of making money through managing statistical risks on life expectancy data are, taken together, a very big business indeed.

So here an insurance conglomerate is, as many of them are, sponsoring an event to help spread knowledge through the system: from scientists to actuaries to risk managers and other decision makers in the food chain. Building bridges and forming communities is in and of itself a form of risk management in the long term: it is a way to lower the likelihood of unpleasant surprises by trying to better understand what the scientific community believes are likely outcomes for longevity science over the decades ahead.

Some quotes from the conference site:

We are living in an era of radical change. Longevity offers us all an opportunity to make more ambitious life choices and look to the future with renewed hope. This is why it is vitally important that we move quickly to meet the challenges which it poses for our society.

Drawing on its expertise as an insurer, AXA is playing its part by creating a space to convene an exchange between decision-makers and experts working to ensure this phenomenon is better defined and fully grasped: the Global Forum for Longevity.

…

Our conviction as an insurer and observer of demographic and societal changes worldwide, is that longevity is not a fate to be endured but instead an opportunity. We need to respond quickly in order to meet the challenges which it poses to our society.

“Challenges.” One thing to bear in mind here is that the big insurance groups are inextricably tied in to the unsustainable pension promises made by politicians past and present in many countries around the world – unsustainable even with modest increases in longevity, never mind what is likely to result from the biotechnology revolution. So there is a certain amount of long term public relations work being undertaken by various parties so as to avoid becoming the sacrificial goat in the end when the system of entitlements collapses. You can make your own decision as to how much of the motivation behind this conference falls into that bucket versus the knowledge transfer aims discussed above.

Empires end when an entrenched elite can spend from the public purse and take on debt without immediate consequence or forethought, destroying the value of their currency in the process. Assuming (perhaps optimistically) that present economic empires survive the next couple of decades, a combination of foolish promises and increasing human longevity will be the rock that sinks them.

Nanotechnology can be used to build assemblies of designed molecules that seek out specific cells – such as cancer cells – but an alternative approach to targeted therapies is to build machinery large enough to be controlled from outside the body, such as the microcarriers demonstrated here: “Soon, drug delivery that precisely targets cancerous cells without exposing the healthy surrounding tissue to the medication’s toxic effects will no longer be an oncologist’s dream but a medical reality … sing a magnetic resonance imaging (MRI) system, [researchers] successfully guided microcarriers loaded with a dose of anti-cancer drug through the bloodstream of a living rabbit, right up to a targeted area in the liver, where the drug was successfully administered. This is a medical first that will help improve chemoembolization, a current treatment for liver cancer. … The therapeutic magnetic microcarriers (TMMCs) [are made] from biodegradable polymer, [measure] 50 micrometers in diameter – just under the breadth of a hair – [and] encapsulate a dose of a therapeutic agent (in this case, doxorubicin) as well as magnetic nanoparticles. Essentially tiny magnets, the nanoparticles are what allow the upgraded MRI system to guide the microcarriers through the blood vessels to the targeted organ. During the experiments, the TMMCs injected into the bloodstream were guided through the hepatic artery to the targeted part of the liver where the drug was progressively released.”

Link: http://www.eurekalert.org/pub_releases/2011-03/pm-wf-031511.php