In order to identify cancer causes and prevention strategies, researchers conduct
cohort studies where they collect information from large groups of individuals
over many years. Through surveys and interviews, participants answer questions
about their daily diet, physical activity, health history, and other lifestyle
conditions. A number of cohort studies have linked diet to a higher risk of prostate,
breast and colon cancers.
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Diet and Cancer
Diet – specifically a “Western” diet high in red meat – is one lifestyle condition that has been linked to the development of prostate cancer.
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William Nelson, M.D., Ph.D. is a researcher at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. HIs research focuses on the molecular causes involved in the development of prostate cancer. This has led to the discoveries that inflammation, diet, and gene "silencing" have roles in prostate cancer development.
Well there's one piece of what's called ecological epidemiology evidence that's very strong and dominates many of our thinking, much of our thinking about prostate cancer. And that's a man born in rural Asia, who lives his life in rural Asia, is very unlikely to develop prostate cancer and very unlikely to die from the disease. Now granted they don't screen for prostate cancer there, but mortality rates are reasonably solid that they're very unlikely to die from prostate cancer. And yet when Asian men immigrate to the Western world – so there's been a nice study done where they immigrate to North America – they begin to adopt a risk of prostate cancer that is more consistent with Caucasians and other residents of North America than the area which they left. And they adopt it quickly. If they were here ten years or less, the risk is like they never left Asia, if they're here 25 years or more their prostate cancer mortality risk is about half that of Caucasians. Ethnic Asian men born in this country have a risk that is very close to that of Caucasians. This very strongly suggests that there is something in the environment that is driving the epidemic of prostate cancer in the Western world.
There's something about diets of folks who get prostate cancer that are a little different from the diets of folks that don't. And it is in every way, a bad diet if you will, a stereotypical Western diet – too much dietary fat, particularly too much animal fat, probably even too much animal fat from red meat and not enough fruits and vegetables, antioxidants, micro-nutrients, and the like. People eat a pound, a pound and a half, two pounds of food a day. And it is one of the most complicated chemical mixtures that you can even ponder. There's all kinds of things in food. There are things that we know of in food related to the way food is processed which can clearly cause cancers. One we worked on a little bit is a compound that appears in meats – chicken, steak, hamburgers and cheeseburgers and whatnot. Depending on how it's prepared or how it's cooked. If they're grilled or cooked to a very high temperature, there's a reaction between high- energy phosphate- containing energy molecules in flesh foods like phosphocreatine and amino acids like phenylalanine and others. Just the heat will drive this reaction to create a variety of carcinogens that are called heterocyclic amines. Red meats can form another set of carcinogens as well. If you watch a hamburger on the grill, you'll notice that the fat tends to melt when you grill it and as it melts, it drips out and becomes charred and you make these polycyclic aromatic hydrocarbon type compounds. You could say, wait a minute, heterocyclic amines, polycyclic aromatic hydrocarbons, what are these things? Well you make the same things when you light a tobacco leaf on fire. In one case, you smoke them, which we know is not good for you. In the other case, we ingest them, which we suspect is not good for you.
The prostate is actually a male sex accessory gland that surrounds the urethra, the urine tube, as it comes out of the bladder in men, before the urethra goes into the penis. Its function, it contributes about a third of the secretions to the ejaculate for sexual reproduction. Today the dawn of the new millennium, we still do not know exactly what these secretions are needed for. The sperm are capable of fertilization in the absence of the prostate secretions. Removal of the prostate gland creates other difficulties with sexual reproduction but not related to what the sperm need to do.
Meat cooked at high temperatures can produce chemicals that are damaging to cells and DNA. The body has a whole range of enzymes that react with these chemicals to render them inert for eventual disposal. One such enzyme seems to be inactivated in men with prostate cancer.
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William Nelson, M.D
John Hopkins School for Medicine
Prostate cancer has become a major scourge for men as they age in the developed world. About 1 in 5, or 1 in 6 men are likely to be diagnosed with prostate cancer in their lifetime.
The gene that appears to be most commonly inactivated in prostate cells as they become cancerous is a gene that encodes a glutathione-S-transferase enzyme.
This is an enzyme that can take a chemical scavenger molecule, glutathione, which is typically present at millimolar concentrations inside cells, it can take that scavenger and conjugate it to threatening reactive chemical species whether they be oxidants, reactive oxygen species if you will, or carcinogen-like things.
GSTP1 doesn't seem to be a gene in prostate cancer at least that's controlling growth, invasion, or metastasis or something that you might imagine a classical tumor suppressor gene to do. Rather, it seems to be a gene that controls the vulnerability to further gene damage by reactive oxygen species and carcinogens. So in that sense it acts more like a repair enzyme that is protecting the genome against damage.
So the GSTP1 gene is inactivated via a mechanism that appears to be very common in most human cancers. It has a gene promoter, a transcriptional promoter region that is a classic CpG island.
What a CpG island is, is that the nucleotide sequence C followed by G is self-complementary and it's relatively underrepresented overall in the human genome. But often when it's found, it's found clustered into regions of about a kilobase in length.
When it's clustered in these regions, in most normal genes, the C does not carry a 5-methyl modification.
We now know that it's also a common mechanism by which genes are turned off in cancer cells. So they carry this region methylated. And GSCP1 is a very classic example of this actually. Its CpG island is quite densely occupied by CpG dinucleotides, and basically in almost every single case both copies of the genes are present and both are methylated.
In addition to enzymes produced by the body, certain components in food can also react with damaging chemicals. An increased consumption of these foods may lower a person’s risk of cancer development.
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Leafy green type vegetables have chlorophyll and chlorophyll is a remarkable energy scavenger. And there is some hint that if you consume chlorophyll you can intercept reactive kinds of chemical species, things might damage proteins, DNA, RNA inside the cell. You might intercept them before they get into the cell and cause damage and then protect against cancer involved with those. And that's just the beginning. There are all kinds of things in food. I think fruits and vegetables are very likely to be protective. I think a safe recommendation at this point is the one that American Cancer Society makes which is try and get in five servings of fruits and vegetables a day. But I think as we learn more and more and more about them, we begin to understand almost to a therapy kind of degree what we're actually eating.
Walter Willett is the Fredrick John Stare Professor of Epidemiology and Nutrition at the Harvard School of Public Health. HIs research focuses on how dietary factors may contribute to and cause health-related conditions. He has written a book Eat, Drink and Be Happy, which summarizes some of the results from his research.
For overall cancer reduction by diet, the most important thing is keeping calories in balance with our physical activity, which means staying as lean and active as we can throughout our life. There’s quite a bit of evidence that high consumption of red meat is related to several cancers, probably colon cancer and probably prostate cancer as well. So, replacing some of the red meat with poultry, some legumes, beans, and fish, and nuts is a good thing to do. We know that’s very helpful from the standpoint of cardiovascular disease and probably useful from a standpoint of cancer prevention as well. Eating a lot of fruits and vegetables has been widely advocated as a means of reducing cancer risk and there possibly is some benefit from that. But it’s I think pretty clear that it’s not nearly as powerfully cancer preventive as we had hoped a few years ago. And it may turn out that it’s much more specific than cancer overall. For example, we have seen that men who consume more tomato products high in a substance called lycopene have a lower risk of prostate cancer, but when we look at fruits and vegetables overall, we don’t see much relationship with prostate cancer risks. So, this may have to come down to specific components of fruits and vegetables and specific cancers.
We can't be 100% sure if the lycopene from a supplement is really going to be the same as eating tomatoes, which are high in lycopene. First of all, what we see in our studies is that people who eat more tomatoes and tomato products have had a lower risk of prostate cancer. And it's a hypothesis that lycopene is the active agent but it's actually possible that it's something else in tomatoes or the combination of several factors in tomatoes that's related to lower risk of prostate cancer. And it will really require a separate study giving supplements of lycopene for many years to see if that specifically was the active factor that was related to lower risk of prostate cancer and that study hasn't been done yet.