Respectful Insolence

The New York Times has been periodically running a series about the “40 years’ war” on cancer, with most articles by Gina Kolata. I’ve touched on this series before, liking some parts of it, while others not so much. In particular, I criticized an article one article that I thought to be so misguided about how the NIH grant system leads researchers to “play it safe” and how we could cure cancer if we could just fund “riskier” research that I had to write an extended screed about the misconceptions in the article. The latest installment, Medicines to Deter Some Cancers Are Not Taken, also by Kolata, is much better in that it discusses a problem at the heart of cancer, namely that we have developed drugs that can decrease the risk of specific cancers but they are not as widely used as they could be.

The first part of the article contrasts a seeming incongruity:

Many Americans do not think twice about taking medicines to prevent heart disease and stroke. But cancer is different. Much of what Americans do in the name of warding off cancer has not been shown to matter, and some things are actually harmful. Yet the few medicines proved to deter cancer are widely ignored.

Take prostate cancer, the second-most commonly diagnosed cancer in the United States, surpassed only by easily treated skin cancers. More than 192,000 cases of it will be diagnosed this year, and more than 27,000 men will die from it.

And, it turns out, there is a way to prevent many cases of prostate cancer. A large and rigorous study found that a generic drug, finasteride, costing about $2 a day, could prevent as many as 50,000 cases each year. Another study found that finasteride’s close cousin, dutasteride, about $3.50 a day, has the same effect.

This is indeed a contrast. Think about it. Millions of Americans take statins, for instance, to lower their cholesterol and thereby try to prevent the complications of elevated cholesterol, such as heart disease, vascular disease, and strokes. Yet, for at least two common cancers, there are proven effective drugs that will lower the risk of cancer considerably with a side effect profile at least as favorable as that of statins.

Of course, preventing cancer is not like preventing heart disease. “Cancer” is not a disease, but many diseases arising from many different organs with many different biological behaviors. There is no drug that can prevent “cancer.” There are, however, specific drugs that can lower the risk of specific cancers. So right there you have a big difference that could partially explain the reticence. Which cancers should be prevented? How many different drugs are you willing to take to prevent how many different cancers?

One thing that the article points out that is quite true and has been quite disappointing to cancer researchers, and that’s that diet does not have nearly as large an effect as we had hoped. Kolata correctly points out that if we could eliminate smoking cancer deaths would decrease by about a third. Lung cancer is quite rare in nonsmokers. Indeed, back in the early part of the 20th century, lung cancer was so rare that there are reports describing how, when a patient died of it, medical students would be told that they had to go to see the autopsy because they might not ever see another case in their careers. Now lung cancer is the single largest cause of cancer deaths in both men and women, causing 30% of cancer deaths in men and 26% of cancer deaths in women, and it’s all due to smoking:

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No other preventative intervention could conceivably even come close in terms of effect as cutting smoking to zero. Obviously, such a thing will not come to pass in my lifetime, but as a cancer surgeon I can always hope, can’t I? Also as a human being, too. After all, I’ve already lost an aunt to smoking-induced lung cancer in 2008, and I have several relatives who smoke who, I fear, might well join her.

After that, Kolata suggests that avoiding hormone replacement therapy containing estrogen and progestin after menopause would be a good preventative, which may be true, but since the Women’s Health Initiative study reported in 2002 that showed an increased risk of breast cancer from such HRT, few women take them any more anyway.

What’s more interesting is how Kolata correctly points out just how little diet and other lifestyle factors seem to matter compared to our hopes. If anyone wants to counter the claims of woo-meisters that we evil “allopathic” doctors don’t pay attention to diet and lifestyle, one only needs to look at just how much money has been spent on studies of diet and exercise and how they impact cancer and heart disease. There have been many studies. Of course, it’s incredibly difficult to do a randomized study, particularly a double-blinded one, of diet and exercise; so most of them end up being observational. The problem with such studies is, as with all such cohort studies, controlling for confounders. It’s hard enough to control for confounders that the investigators know about, but there are often many confounders that they don’t know about and may not identify until after the study is over. In any case, suffice it to say that studies of diet as a means of preventing cancer have been disappointing of late, as Kolata points out:

For example, public health experts for years recommended eating five servings of fruits and vegetables a day to prevent cancer, but the evidence is conflicting, at best suggestive, and far from definitive.

Low-fat diets were long thought to prevent breast cancer. But a large federal study randomizing women to a low-fat or normal diet and looking for an effect in breast cancer found nothing, said its director, Ross L. Prentice of the Fred Hutchinson Cancer Research Center in Seattle.

Fiber, found in fruits, vegetables and grains, is often thought to prevent colon cancer, even though two large studies found no effect.

“We thought we would show relationships that were strong and true,” said Dr. Tim Byers, professor of epidemiology at the Colorado School of Public Health, “particularly for dietary choices and food and vegetable intake. Now we have settled into thinking they are important but it’s not like saying you can cut your risk in half or three-quarters.” Others wonder whether even such qualified support is misplaced.

There has to be a reason the research disappointed, said Colin B. Begg, chairman of the department of epidemiology and biostatistics at Memorial Sloan-Kettering Cancer Center. Perhaps the crucial time to intervene is early in life.

“That’s one possibility,” Dr. Begg said. “The other is that it’s all sort of nonsense to begin with.”

One potential reason for these results is that the effect of diet or other environmental exposures may have a “window of vulnerability” that occurs in youth or childhood. Certainly, in the breast cancer field, we are starting to think that and actively research the possibility. The problem is, if that’s true, then dietary interventions during adulthood may have little or no effect on ultimate cancer risk.

Which brings us to drugs and supplements.

Kolata mentions the cautionary tales of beta-carotene and selenium, the former of which was thought to prevent cancer and the latter to prevent prostate cancer. However, when a large study of beta carotene was done, not only did the supplement not prevent cancer but it appeared to increase the risk of lung cancer in smokers. Selenium and vitamin E similarly were found to have no protective impact on prostate cancer risk and, in fact, the trial studying the question was halted because there was a hint of actually increased risk. Even so, as Kolata points out, ads for such supplements continue to imply, with the Quack Miranda warning, that such supplements “improve prostate health,” whatever that means, although the implication is that they decrease the risk of prostate cancer.

Now here’s where the drugs come in. Because I’m a breast cancer surgeon, I’m going to focus mainly on strategies to prevent breast cancer. It turns out that tamoxifen can decrease the risk of breast cancer by 50% in high risk women. Tamoxifen is a selective estrogen receptor modulator (SERM) that antagonizes estrogen action in breast tissues but has partial agonist activity in bone and endometrium. Indeed, raloxifene, another SERM, is used primarily to prevent and treat bone loss in women with osteoporosis. A $110 million clinical trial showed that its ability to prevent breast cancer is not statistically significantly different than that of tamoxifen, with the advantage that, unlike tamoxifen, raloxifene does not increase the risk of uterine cancer and does not increase the risk of blood clots as much as tamoxifen does.

So, with such overwhelming evidence that in women at high risk for breast cancer, why is it that so few are offered the option of tamoxifen or raloxifene? Kolata explains:

“Those were your tax dollars and mine,” he [Dr. Victor Vogel] added. “You can’t do too many $110 million studies.”

He cannot understand why no one cares, but some doctors say they see a number of problems. It is usually not the cost; tamoxifen is about 30 cents a day and raloxifene $3.30 a day. It is doctors’ practices and women’s concerns.

Most doctors, said Dr. Therese B. Bevers, medical director of the Cancer Prevention Center at M. D. Anderson, do not take the first step — calculating a woman’s lifetime risk of getting breast cancer — in part because that can lead to the next step, spending an hour or so discussing cancer risk and drug risks and benefits.

Dr. Bevers suggests the drugs for women whose lifetime odds exceeds 20 percent. That could include, for example, a 55-year-old woman who began menstruating early (increasing the risk), had her first child late (again increasing the risk), and whose mother and sister got breast cancer. About half the time, though, women with that kind of risk turn down the drugs, Dr. Bevers said. “The No. 1 reason I hear is, ‘Oh, I just don’t like to take medications,’ ” she added.

Yet the same women will happily down supplements that woo-meisters like Dr. Mercola or Mike Adams will suggest to them as cancer preventing. Some will down many supplements a day without thinking twice about it, even though there is no good evidence that they do anything other than enrich the supplement manufacturers who make them and they often cost far more than the paltry 30 cents a day that tamoxifen costs. Moreover, in general for prevention the usual course of tamoxifen or raloxifene is five years, in marked contrast to supplements, where the woo-meisters recommend them for the rest of one’s life.

Of course, never having worked anywhere else other than NCI-designated comprehensive cancer centers, I am probably spoiled in this respect. Such centers always have genetic counseling and prevention clinics. I can simply refer suitable patients there, where our trusty and excellent genetic counselors will calculate patients’ lifetime risk of breast cancer, construct family trees, decide if testing for cancer susceptibility genes is appropriate, and then make science-based recommendations for risk prevention strategies and/or screening strategies tailored to the individual patient. (Who says “allopathic medicine” doesn’t individualize therapy?) In any case, I can see why primary care doctors don’t bring these issues up more often, but with the advent of genetic counseling clinics I am puzzled why more patients aren’t referred to a specialist for these conversations.

One problem mentioned in the article is that there aren’t any particularly good biomarkers for increased risk for cancer, especially ones that fall in response to preventative interventions, the way, for example, cholesterol does for heart disease. Another is what I mentioned earlier, namely that cancer is not one disease, meaning that it is likely that many drugs would be needed to prevent various cancers. True, for the really common cancers, like prostate, breast, and colon, it might be worth it to develop such drugs, but neither the risk-benefit profile nor the number of patients who would benefit would be likely to lead to such drugs for less common cancers. And, as has been pointed out, our risk assessment tools are currently crude at best. In fact, even with better biomarkers I’m not so sure that interest would improve because biomarkers have their own problems and many people have a tendency to fear pharmaceuticals more than they fear a hypothetical increased risk of cancer. In the case of drugs that prevent breast cancer, nearly all of them have anti-estrogen activities and thus produce side effects of estrogen deprivation, such as hot flashes and other menopausal symptoms. It’s a very high bar to meet to produce effective drugs that people will actually take, given that it’s hard enough to persuade patients to comply with drugs designed to treat actual diseases and conditions.

The end result of all of this is that drug companies, once interested in developing cancer preventing drugs, are now floundering. As Kolata notes:

But risk assessment is not easy, and biomarkers are still more of a dream than a reality. There are other problems, too. If each cancer requires a different drug for prevention, how many drugs can a person take? For now, Dr. Curt said, the very idea of cancer prevention is daunting. And since cancer can take decades to develop, by the time a study concludes, a drug’s patent life may be over.

It is not a pretty picture, Dr. Vogel said.

“You have to think that in boardrooms they are saying, Man, did we learn a lesson,” he said. “We will stay as far away as possible from cancer prevention.”

Sadly, supplement manufacturers are not faced with such problems because they don’t actually have to demonstrate that their supplements have the health effects that they claim they have. The war against cancer goes on, but one weapon is not being developed.

Comments

  1. #1 katie
    November 16, 2009

    I know this is irrelevant and juvenile, but all I could think of while reading this was: “If you like Gina Kolata, gettin’ caught in the rain”….

  2. #2 John Wlehc
    November 16, 2009

    “I am not into health food, I am into raloxifene”

  3. #3 Gus Snarp
    November 16, 2009

    You really answered the question quite well with: “nearly all of them have anti-estrogen activities and thus produce side effects of estrogen deprivation, such as hot flashes and other menopausal symptoms”. It’s pretty hard to convince a healthy person to take a drug with known side effects because of some abstract risk numbers. I think it is reasonable to be concerned about the notion of taking a drug every day in the hopes that your cancer risk will be reduced. It seems a little creepy, a little Fahrenheit 451. Oh, and there are plenty of people who don’t like to take medications if they don’t absolutely have to who also wouldn’t go near any of these ridiculous “supplements”.

    What’s stunning is the rates of lung cancer and death from lung cancer. Is that world wide? U.S.? Europe? As I understand it, only about 20% of Americans smoke, so if those rates are from the U.S., well it’s pretty stunning any way you look at it. Amazing that people still not only smoke, but will defend smoking.

    With all the talk about the effectiveness of diet on cancer prevention, you didn’t mention lycopene and prostate cancer. Has that been found wanting as well?

  4. #4 Gus Snarp
    November 16, 2009

    @katie – Brilliant. LOL.

  5. #5 Kemist
    November 16, 2009

    I used to work in a lab that developped SERMs. They came up with a great new drug, EM-652, which had a excellent profile : bone loss preventive, cardiovascular protectant, showed activity in patients which had become resistant to ralox, and better activity than ralox in vivo assays (this was one of my friend’s grad studies work)…

    But everything crashed – aromatase inhibitors are the new hype in cancer HT. And no one is interested in taking an evil “synthetic” hormone as a preventative. This drug’s developper now works on DHEA with an investment from l’Oreal. On anti-wrinkle creams.

    Why is it that people are ready to take inordinate risks for their appearence (plastic surgery carries the same risks as the life-saving kind), but can’t be bothered to do something that might save their lives ?

    That’s one great new drug that will probably never be used. I’m sure there are lots of others sleeping on the shelves everywhere.

    And people wonder why there’s not that much cancer research in pharmas.

  6. #6 Gus Snarp
    November 16, 2009

    @Kemist – Because they see (or expect to see) results in their appearance. Telling them their risk of cancer will be reduced is just too abstract for people. Heck, that’s why supplements sell better than real preventatives. Supplements makers lie and say: “this will prevent cancer”. Real drug makers have to say: “this will reduce your risk”. People aren’t going to do it unless they are told “you won’t get cancer”. It’s just human nature. We are really bad at risk analysis.

  7. #7 Anthro
    November 16, 2009

    @Katie – I’ve had the same reaction every time (for many years) that I see GK’s byline. LOLLL

    Kudos to John W as well for the very funny follow up.

    Now for the topic: I’m not giving up on healthful eating, because I LIKE healthy food and I can’t believe it would do any harm. I’m at very low risk for breast cancer, but would happily take tamoxifin if advised to do so by a doctor. Perhaps because I started on life-saving statins and BP meds at an early age (40) due to family history of heart disease, I got over that “oh, I can’t start taking pills” attitude early on. Years ago I went through a supplement “phase” and found, however, that I could not gag down the huge (size of pill and quantity of pills) amounts the supplier recommended.

    I would wonder, however, about the obesity connection to cancer–does that hold up? If so, then there is a food connection. The drugs I mention helped me, but I still got a stent at age 49 (no heart attack, but close). Not until I lost 45 lbs (maintained) did my levels normalize and I still take a small dose of statin to keep my levels extra low because of family history. The weight loss also resulted in normal blood sugar after years of borderline diabetes.

    While the main cause of the weight loss was to take in less calories, I also made those calories count in nutritional terms and I don’t take any vitamins. So maybe my cancer risk isn’t lower due to healthy food, but healthy food helped me lose 45 lbs, which I think (?) lowers my cancer risk as well as “curing” my heart disease and diabetes. If I had lost weight by eating only 1000 calories of Cheetoes per day, would my cancer risk be the same?

  8. #8 Kemist
    November 16, 2009

    You really answered the question quite well with: “nearly all of them have anti-estrogen activities and thus produce side effects of estrogen deprivation, such as hot flashes and other menopausal symptoms”. It’s pretty hard to convince a healthy person to take a drug with known side effects because of some abstract risk numbers.

    Most women who would benefit from SERMs as preventatives are already menopaused (breast cancer risks increase after menopause). Actually, people like my mother, who has much nastier side effects from menopause than hot flashes (she has terrible debilitating hormonal-variation-induced migraines) would probably benefit, symptom-wise, from taking ralox or tamox.

    I think it is reasonable to be concerned about the notion of taking a drug every day in the hopes that your cancer risk will be reduced.

    I take a drug called synthroid every single day to avoid complications from hypothyroidism. I don’t mind it at all – if it didn’t exist, I would end up in a pretty sad state. The “natural” outcome of hypothyroidism is an unpleasant death (myxedema coma).

    Similarly, if I had seen my mother, sister and cousins die from breast cancer, I would not mind taking a SERM as prevention in the slightess.

    People seem much less reluctant about taking so-called “natural” things. Most people, for example, don’t mind taking aspirin as a heart-disease preventative (even though it can make them have quite debilitating stomach issues – I can’t take even one aspirin without vomiting), but statins are teh evull, despite their good profile.

    I have an aunt who gorges on “natural”, at best useless, supplements, but can’t be bothered to take the statin that might save her from a heart attack – she has alarmingly high blood pressure and high LDL which made the local blood drive turn her away as a donor.

    There’s no reason at all behind that behavior – just fear.

  9. #9 Andreas Johansson
    November 16, 2009

    @Gus Snarp: 21% of adult Americans smoke according to http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5542a1.htm

    (That’s pretty much the same prevalence as in my native Sweden, which somewhat surprises me as I’ve been told Americans smoke much less than we do.)

  10. #10 Gu
    November 16, 2009

    @Kemist – Taking a drug daily for a condition is different from taking a drug daily to reduce the risk of a condition. The only point I’m trying to make is that this is an understandable hurdle in human psychology. We are not intuitively good at doing this kind of risk analysis. We may make the wrong decision from a mathematical point of view, but that doesn’t mean that it’s ever going to be easy to convince people otherwise.

  11. #11 Kemist
    November 16, 2009

    If I had lost weight by eating only 1000 calories of Cheetoes per day, would my cancer risk be the same?

    Maybe eating a 1000 calorie worth of cheetos would have helped almost as much against cancer risks, but I think you would have ended up in a serious deficiency state. Those vitamins, essential amino- and fatty acids may play a minor role in cancer risk, but they are necessary for your health. For example, a severe vitamin A deficiency can make you go blind.

    Additionally, getting cancer for an otherwise healthy person is not the same as, for example, getting cancer if you are suffering from heart disease. If that were the case and you were unfortunate enough to develop cancer, you would be unable, for instance, to withstand treatment with doxorubicin, a drug with known cadiotoxicity. In each person’s personnal war against cancer, the loss of such a weapon can make the difference between life and death.

  12. #12 Denice Walter
    November 16, 2009

    @ Andreas Johansson:I think that if you look at the CDC smoking prevalence data *by state*,you’ll see that certain states/regions of the US *do* smoke less…. and *more* (it’s easily observable if you travel around the country).There is also a socio-economic factor.

  13. #13 Nathan
    November 16, 2009

    Another example of science-based medicine losing out because it does not fall along the path of least resistance – both financially and public-relations wise. It never gets any less frustrating.

  14. #14 Eric
    November 16, 2009

    I find it interesting that you so quickly agree with the article’s contention that diet has no effect on cancer. How does one explain the many societies around the world where many cancers are quite rare? Is is language, geography, genetics? How to explain the rise in cancer rates these societies see when their members emigrate to the West, or adopt Western diets?

    The researchers quoted in Kolata’s article all point to very limited studies conducted on people in the West and in the US who have been eating primarily rich Western diets for their entire lives. Somehow we’re supposed to see some kind of difference when they start eating a few more fruits and vegetables late in life. If you look at the fact that cancer rates for many common forms of cancer are dramatically lower in several societies around the world, including most Asian nations, and that people from these regions that move to the US see their cancer rates rise to our levels, there clearly is a lifestyle/diet connection that is vastly more profound than what these limited studies have ever found. It is clear when looking at Okinawans, or certain indigenous populations in Mexico, and other areas, that there are diets that when consumed from childhood, dramatically lower ones chances of getting cancer. Part of the answer is probably that these diets are dramatically different than ours. They consume almost no animal products, no dairy, no processed grains, and very little fat. To give a few extra fruits and vegetables to Westerners who still eat mostly animal products and expect to reduce cancers to these levels is silly. Even sillier is to pull out a few chemicals out of individual foods and think that they can be isolated in miracle cures when each whole food has thousands of chemicals that impact health in ways we do not understand. It is clearly the whole of the food that gives benefits to health, and isolation of individual chemicals is a fool’s journey.

    If we were really serious about finding the diet/cancer link, wouldn’t it make sense to just eat like societies where they don’t have our cancer rates. Wouldn’t it be nice to cut breast cancer rates dramatically? Rather than spending billions on drugs that will never work, why not just do what others are doing. In short, eat like an okinawan, a mexican hill tribe, or one of several other societies. We’re just too busy spending billions in a misguided infatuation with technology to see that the answer is right at the end of our forks.

  15. #15 ebohlman
    November 16, 2009

    Gus: Smoking-induced lung cancer takes decades to develop, so there’s little relationship between a country’s current smoking rate and its lung cancer incidence. 40 or 50 years ago, a much higher percentage of Americans smoked, and it’s mainly the people who smoked then who are getting lung cancer now.

  16. #16 John Coleman
    November 16, 2009

    How about saw palmetto for Prostate health? Any comments?

  17. #17 Orac
    November 16, 2009

    I find it interesting that you so quickly agree with the article’s
    contention that diet has no effect on cancer.

    Nice straw man ya got there…

  18. #18 Michael Simpson
    November 16, 2009

    @ebohlman. Though your point is right, and this article is about cancer, I believe that the reduction of smoking will have a more immediate effect in the reduction of cardiovascular disease.

    @eric. I’m suspicious of most food/disease claims, though there are clearly environmental effects on certain cancers. To make a claim that the Okinawan diet prevents all cancers (which it clearly does not), a low fat, high fiber diet does have some benefits.

  19. #19 Kevan Gelling
    November 16, 2009

    there aren’t any particularly good biomarkers for increased risk for cancer

    Is 25(OH)D a good biomarker for breast cancer? There have been a number of news stories recently that have linked breast cancer and low calcidiol levels.

  20. #20 Gus Snarp
    November 16, 2009

    @ebohlman – Excellent point, thank you.

  21. #21 Scientizzle
    November 16, 2009

    @ John Coleman: How about saw palmetto for Prostate health? Any comments?

    Plug this number in to Pubmed for the recent Cochrane review – PMID: 19370565. “AUTHORS’ CONCLUSIONS: Serenoa repens was not more effective than placebo for treatment of urinary symptoms consistent with BPH.”

    Regarding prostate cancer specifically, a 2006 study found “use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk” (PMID: 16965237).

  22. #22 Kemist
    November 16, 2009

    If we were really serious about finding the diet/cancer link, wouldn’t it make sense to just eat like societies where they don’t have our cancer rates.

    1)It’s not the rates for all cancers that goes down in those places. I’m not sure, knowing the differences in mortality and morbidity, that I would like to exchange a lower breast cancer incidence with a higher stomach and oesophage cancer rate (both of these are more frequent in asia than here).

    2)In many of those countries (with the exception of Japan), cancer is rarely diagnosed correctly because most people can’t afford to see a doctor, much less a cancer specialist. Cancer rates from India, China or indigenous mexican tribes are mostly meaningless.

    3)Is it the different food per se that is the problem in immigrants or simply their obesity stats, which suddenly start to resemble those of their “Western” counterparts because they have started using their cars more than their legs ? Or the difference in screening and diagnosis of different cancers ? Or even the decreased amount of daytime light they get here (that is not as silly as it looks : nighttime work has been correlated with an increase in cancer risk) ?

    It is not as simple as it looks. Nothing ever is in biological systems.

  23. #23 Jeff
    November 16, 2009

    In the NY Times article, Gina Kolata defines cancer prevention as a choice between beneficial drugs vs. worthless supplements. After reading the posts in the comment section it’s clear some men aren’t willing to endure the potential side-effects of finasteride for the sake of possible cancer prevention.

    The supplement with the best evidence as a preventive agent is vitamin D. It’s very inexpensive with no side-effects. It will take years to prove conclusively whether vit. D has a preventive effect on breast cancer, but several cell studies and population studies make a strong case for it:

    1. In one study women with the highest levels of vitamin D had a nearly 70% reduction in their risk of breast cancer, compared to women with the lowest vitamin D levels.

    2. In another study women with blood vitamin D levels of approximately 52 ng/mL had a 50% lower risk of breast cancer compared with women who had vitamin D levels below 13 ng/mL.

    The vitamin D Council has a comprehensive list of studies involving Vitamin D and breast cancer.

  24. #24 Matt M
    November 16, 2009

    These generic drugs are cheap; only $2 to $3.50 per day. However, $500 to $1,000 per year suddenly does not sound cheap. Then, in order to prevent cancer the drugs would have to be taken for decades. A lifetime of medication for $30,000 or more, with what to show for it? Not getting an illness?

    I will wait for a more persuasive argument before I start a drug regimen like this. It would have to be as cheap and simple as taking a daily fish oil pill to protect my heart, to get my buy-in.

  25. #25 Scientizzle
    November 16, 2009

    To expand upon Kemist @ #22…

    Don’t discount the variability in genetic profiles of various ethnic groups. To get a sense of the problem, check out PMID: 18034184, which discusses the variability in population founder mutations in the BRCA1 & BRCA2 genes, perhaps the most well-established genes causally linked to cancer risks. The wide variability in the types of mutations and the frequencies at which they occur in different groups studied is illuminating. Some ethnic or cultural group may have a lower risk of (some) cancers (e.g., “certain indigenous populations in Mexico”), and a unique local diet may play an important role in that; however, it would be very difficult to properly evaluate that diet, controlling for genetic differences between populations.

    Much of the “easy” genetics work has been done, identifying gene polymorphisms that have large effects on the prevalence of disease. The frontier is finding those variants that may affect a single person’s lifetime odds of developing a disease in small increments, maybe 0.1% or less.

    And again, the obvious take home message from these types of articles and blog posts isn’t “diet doesn’t matter, so have at it” but quite the opposite: there are many, many positive effects of healthier dietary and exercise lifestyles, but they’re not a magic cloak that will shield one from all risk, thus further research is needed to determine such limitations and to maximize that which we can gain from these health choices.

  26. #26 Ahistoricality
    November 16, 2009

    “The No. 1 reason I hear is, ‘Oh, I just don’t like to take medications,’ ” she added.

    Yet the same women will happily down supplements …

    Orac, while you’re right about most of the substantive issues, I’m disappointed to see you accepting self-justifying anecdotal evidence and then leaping to a secondary conclusion which isn’t supported.

  27. #27 TwoYaks
    November 16, 2009

    Orac, I’d be interested in you talking more about the risk factors for Colorectal cancer. It seems like you’ve discounted diet as a mitigating factor, but that flies in the face of what we’ve been told by the media. We’ve been told for a little bit, now, that red meat puts one at risk for Colorectal cancer…

  28. #28 Scott
    November 16, 2009

    We’ve been told for a little bit, now, that red meat puts one at risk for Colorectal cancer…

    And the media, of course, never hype preliminary or questionable results beyond all sanity.

  29. #29 BB
    November 16, 2009

    Very glad you mentioned diet in your post. Just back from a urology meeting, where people reported that diet was not a risk factor for prostate cancer.

  30. #30 VIcki
    November 16, 2009

    I’ve been trying to eat more fruits and vegetables for years, because I keep seeing medical advice that doing so will be good for me.

    Along the way, I’ve gotten to like quite a few of them, and I eat a lot more salads than I used to.

    Is there any medical reason why I shouldn’t do this? Take as given that I am only eating vegetables I like, and that I am not spending exorbitant amounts of money (except maybe on out-of-season berries and tangerines, which I’m doing because I like them). For this purpose, I’m prepared to stipulate that the fruit and veg aren’t going to prevent cancer or heart disease: the question is just whether any harm will come from continuing to eat five or more servings a day.

  31. #31 Scott
    November 16, 2009

    The evidence that eating plenty of fruits and vegetables is generally good for you is pretty iron-clad, I think. Where it gets dubious is when people try to make particular specific claims for places they’re beneficial. Heart disease? Yeah. Cancer? Apparently not so much. Flu prevention? Nope.

  32. #32 Jim Roberts
    November 16, 2009

    @30

    I think this gets back to what Kemist said in post 11 – while it might not play a strong direct role in preventing cancer, a varied diet certainly helps maintain general health and gives you fewer weaknesses that cancer or cancer treatment can exploit.

    I’ve never read anything that says that eating a balanced diet is bad for you, just that it’s not a paneacea.

  33. #33 Serena
    November 16, 2009

    After undergoing genetic counseling as well as seeing a breast oncologist I have been told that my risk for developing breast cancer is moderate. The only thing suggested to me was a breast mri, exercise and remaining at a healthy weight. Believe me, if it was suggested that I take a drug that reduced my chances of contracting breast cancer I would not hesitate one damn minute. However, I would never take supplements–I just don’t trust or believe in them.

  34. #34 Marishka
    November 16, 2009

    33 drugs and supplements are basically the same things. IF the supplement has been tested it is just another kind of drug too. Anything, drug or vitamin is something you are supplementing your body with. I would choose whichever drug or supplement was approved and had science behind it.

  35. #35 Ken Phillips
    November 16, 2009

    Hey, I’ve been balding for years; maybe I could get a twofer. I feel pretty safe assuming you could get more customers with ‘may stop hair loss’ than with ‘may reduce prostrate cancer risk’.

    #14 & #22: I’ve read about those studies, but haven’t read them. Did they control for environmental variables, ie earth, air and water? I’d assume a more developed country would expose you to different toxins.

  36. #36 Scott
    November 16, 2009

    33 drugs and supplements are basically the same things. IF the supplement has been tested it is just another kind of drug too.

    The problem with this is that, in most cases, the reason to label something a “supplement” is explicitly to AVOID the need to do testing. There are some exceptions (iron supplementation for deficient women, for instance), but if you assume any supplement, not specifically recommended by your doctor to address an identified nutritional deficiency, is completely unproven you won’t be too far wrong.

  37. #37 leigh
    November 16, 2009

    serum vitamin D is correlated with breast cancer incidence, but we have no causative evidence. i observe that wind and rain often occur together, but i know that wind does not cause rain. there is a gigantic logical leap involved to look at those data and state that a particular serum vitamin D concentration will prevent cancer.

  38. #38 Michael
    November 16, 2009

    “If we were really serious about finding the diet/cancer link, wouldn’t it make sense to just eat like societies where they don’t have our cancer rates.”
    In addition to what #22 said, some of those countries have higher rates of other diseases.

  39. #39 passionlessDrone
    November 16, 2009

    Hello friends –

    @Eric – I believe you’ve read the China Study. I did, and changed my habits quite drastically in the meantime.

    One thing that the author of the China STudy would tell you is that it isn’t high fat / low fat, it is, where does the fat come from? Is it animal based or not? This, he claims, is the biggest problem with the large nurse study that seemed to have found no effect on diet; people went from whole milk to skim milk, from red meat to chicken. Campbell will tell you that is the wrong set of metrics to use.

    As far as sublte population level polymorphisms, again, the China Study author referenced studies that showed that if you were born in one of the areas that had low cancer (at least some of them), and moved and adopted a western diet, your chances of some cancers, or any diseases of allfluence sky rocketed. Particularly striking was the difference between siblings, one of whom moved to another dietary lifestyle, and one who did not. I have lent my copy out, and cannot provide the links to support this at this time. :(

    As far as anti cancer effects on vegetables, I seemed to think that I read some abstracts along the way wherein some of the things you get in a vegetable rich diet (i.e., leutolin, flavonoids) inhibit things that tumors use to grow (i.e., VEGF).

    Anti-carcinogenic effects of the flavonoid luteolin

    Inhibition of cell growth and VEGF expression in ovarian cancer cells by flavonoids

    Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3′-kinase activity

    Whether you can get enough of these compounds to have a clinical effect through a vegetarian diet is, I suppose, the next logical question. But it seems likely there is a valid reason that people are asking these types of questions.

    – pD

  40. #40 gaiainc
    November 16, 2009

    In any case, I can see why primary care doctors don’t bring these issues up more often, but with the advent of genetic counseling clinics I am puzzled why more patients aren’t referred to a specialist for these conversations.

    As a PCP, some reasons why patients don’t/won’t get referred:

    1) Insurance. Trying to find the right ICD-9 code so that the insurance will cover the referral or finding one that doesn’t doom the patient to poor coverage for the rest of their lives is sometimes well-nign to impossible. If insurance doesn’t cover my patients aren’t up to coming up with the cost themselves.

    2) Distance. I work in a clinic that is 20-25 miles from an university health center plus at least two other medical systems. My patients will only go into the big city if they have no other choice and it is usually accompanied by a lot of whining, moaning, and bitching.

    3) Availability. I don’t know if most of the doctors even know that this is an option. Seriously. It’s not something that my university’s genetics department advertises.

    4) Cost. For some of my patients a drug that costs $2-4/day is prohibitive. Tamxifen is more reasonable, but without a guarantee that they will not get cancer, good luck on getting my patients to stick to it, particularly if they get hot flashes, night sweats, and other menopausal symptoms.

    I’m not saying that theses reasons are right or wrong. I wouldn’t even argue that they are logical. They just are.

  41. #41 Jeff
    November 16, 2009

    @Leigh: “serum vitamin D is correlated with breast cancer incidence, but we have no causative evidence.”

    Orac often says not to confuse correlation with causation. Fair enough. And there have been no placebo-controlled cancer studies using vit. D. But there is a growing body of scientific evidence showing plausible ways vitamin D could inhibit breast cancer cells. There’s this study:

    http://www.wellnessresources.com/studies/entry/vitamin_d_helps_prevent_breast_cancer

    “Calcitrol, the active form of vitamin D, has been found to induce a tumor suppressing protein that can inhibit the growth of breast cancer cells, according to a study by researcher Sylvia Chistakos, Ph.D., of the UMDNJ-New Jersey Medical School.”

  42. #42 Andreas Johansson
    November 16, 2009

    Denice wrote:

    @ Andreas Johansson:I think that if you look at the CDC smoking prevalence data *by state*,you’ll see that certain states/regions of the US *do* smoke less…. and *more* (it’s easily observable if you travel around the country).There is also a socio-economic factor.

    If you look at Swedish smoking data broken down by region, gender, age, and socioeconomic class, you’ll find significant differences. The same could, I expect, be said of most countries. It doesn’t seem directly relevant, however, to a claim that Americans smoke less than Swedes, which presumably refers to national averages.

  43. #43 Kevan Gelling
    November 16, 2009

    @leigh #37

    no causative evidence

    Yes there is – Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial (Lappe et al. 2007). A 50% reduction in breast cancer occurrence was observed – D3 + Ca vs placebo.

    there is a gigantic logical leap involved

    It’s not a gigantic leap, if you look at the metabolism of calcitriol. It has been shown in the laboratory to be involved in the regulation of cell propagation, differentiation, apoptosis and angiogenesis. It also suppresses aromatase

  44. #44 Margaret Polanezky, MD
    November 16, 2009

    I thought the article read more like cancer prevention as a failed pharma marketing campaign, and did not place the use of these medications, which are cleary not without risk, into an overall context for healthy individuals. In additon, it does not ask how the use of these drugs fits in with our overall “war” on cancer. (See my recent post on the article if you have time to waste -http://theblogthatatemanhattan.blogspot.com/2009/11/drugs-for-cancer-prevention-ny-times.html)

    Are we really willing to say that all men over 50 should take a drug to prevent a cancer that we are also telling them is not worth screening for because most of the cancers are indolent? That all women over 60 should be considered high risk for breast cancer (as Vogel was quoted to say in the article)and take a drug that increases their risk for stroke and thromboembolism? Do we then put them all on Lovenox because the risk assessment for that drug states they are now at high risk for a clot and should “talk to their doctor” about taking Lovenox?

    It’s just not as simple as painted in the article, which made women look like idiots and primary docs like fools for not jumping on the Tamoxifen/raloxifene bandwagon.

    You are right on target stating that our cancer risk assessment tools are too crude. Give me the equivalent of an elevated LDL for breast cancer and the ability to see it reduce with treatment, and you might get better buy in to pharmacologic cancer prevention.

    The comparison with supplements is a good one, and it is indeed a paradox that folks are willing to use them and not drugs with a proven track record of prevention. We all know why this is – they are not regulated, and the side effects are not known, or if they are, not publicized. But I agree, that this does not make the argument to use Tmaoxifen.

    Thanks for yet another well-written analysis of an article that, while thoughtful, was too one-sided in my humble opinion.

  45. #45 TBTAM
    November 16, 2009

    I meant Kolata’s article was one sided, not yours :)

  46. #46 amphiox
    November 16, 2009

    Would it be at all possible to get some version of tamoxifen or raloxifene, or some slightly modified related compound with equivalent activity, marketed as a supplement instead of a pharmaceutical?

    Maybe that would encourage more people to use them?

    (For added incentive, perhaps we can genetically modify a rose to secrete the substance in the petals, so we can call it a “natural” supplement?)

  47. #47 petersyms
    November 16, 2009

    To everyone demonizing Orac for the whole “diet” thing

    “One thing that the article points out that is quite true and has been quite disappointing to cancer researchers, and that’s that diet does not have nearly as large an effect as we had hoped.”

    LEARN TO READ.

  48. #48 Greta Christina
    November 16, 2009

    Orac: Just wanna say thanks. I’m seeing my OB-GYN NP next month for my routine pap/ mammogram. I fall into some of the high-risk categories — early menarche, no children (I assume “having your first child late” includes “never”). I’ll be asking about tamoxifen and raloxifene. Not sure if I’m high-riskj enough for it to make sense, but it sure is worth asking. So thanks.

  49. #49 Kismet
    November 16, 2009

    Scott:
    “if you assume any supplement, not specifically recommended by your doctor to address an identified nutritional deficiency, is completely unproven you won’t be too far wrong”
    But wrong nonetheless, which is important to keep in mind.

    Re. Vitamin D:
    While Lappe et al. immediately comes to mind, still no study looked at vitamin D and cancer as a *primary* outcome — i.e. the really important stuff. There are no big logical leaps involved, vitamin D is rather promising in preclinical research and *prospective* epidemiology, while mixed, suggests benefits. OTOH it’s not like there was no recent influx of epidemiology showing null results. We just need to test the damn *hypothesis* already and do it in a well-designed RCT(several are in the works)

    However, if we consider the vitamin D data in its entirety it would be almost criminal not to have all older people take 800-1200IU/d, and for everyone else keeping 25(OH)D levels >30ng/ml seems much more prudent than a “wait and see” approach.

  50. #50 Prometheus
    November 16, 2009

    Eric asks:

    ” How does one explain the many societies around the world where many cancers are quite rare? Is is language, geography, genetics? How to explain the rise in cancer rates these societies see when their members emigrate to the West, or adopt Western diets?”

    There are a couple of possibilities:

    [1] Diet – that’s what started a lot of the does-diet-affect-cancer-risk studies.

    [2] Genetics – the prevalence of many cancers varies widely between various ethnic/geographic/cultural groups.

    [3] Socio-economic factors – people from poor regions often die of other causes (malnutrition, malaria, war, etc.) before they reach the age where they might develop cancer.

    Both the former and the latter can explain the oft-stated but rarely quantified assertion that some ethnic/geographical/cultural groups have a higher cancer incidence when they adopt a “Western” diet.

    Curiously, there has been little media attention to those situations when adopting a “Western” diet has led to a decrease in cancer – as has been reported (but, again, not well-documented) with gastric cancer in some Asian groups.

    Prometheus

  51. #51 Darren Scott
    November 16, 2009

    Phew! I’m glad that the diet issue has now been settled once and for all… For a while there I thought that I’d be eating buckets of raw vegetables and fruits forever! What a sucker I was… It’s wonderful to know that some ethical folks have put in a tireless effort and I can now return to pouring cheerios, batter, cheese, milk, ice-cream and soda down my throat, together with my 5 anti-cancer chemicals. The ‘WAR’ on cancer is won, folks!

  52. #52 Chris
    November 16, 2009

    Darren, it is obvious you did not read the article. Plus the issue of diet and cancer is separate from other diet health issues (obesity, diabetes, malnutrition, cholesterol, etc).

    What anti-cancer chemical medications have you been prescribed?

  53. #53 Chris
    November 16, 2009

    Oh, goody… along with having reading comprehension issues, Mr. Scott’s link in his name goes to a very expensive supplement sales page. It seems to be advertising a kilo of green powder for over a hundred dollars!

    Sorry, dear boy, I think I’ll stick to a balanced diet of real food, some of which I grow myself (this weekend plans include planting winter spinach, beets and kale, while trying to get the indoor planters going with basil, and mixed lettuces).

  54. #54 Diane
    November 16, 2009

    Just my two cents…Japanese have a far higher risk of stomach cancer, even (especially? only?) those who eat a “traditional” Japanese diet. Nisei born and raised in the US do not have as much risk for stomach cancer.

  55. #55 hibob
    November 16, 2009

    I think a better way to help people make the decision whether or not to take a preventative drug would be to give them the drug’s effect on all-cause mortality and the drug’s NNT for their cohort. Then explain what those numbers mean. For elderly women taking raloxifene NNT = 84 : 84 women taking raloxifene for 8? years prevents one case of invasive breast cancer; NNT to harm = 216 women taking raloxifene will result in one case of raloxifene related pulmonary embolism.

    So $3.30 a day x 365 x 8 x 84 = $809,424 to prevent one case of invasive breast cancer – I can guess how HMO actuaries would look at that.

    There was no difference in total mortality between women taking raloxifene or placebo for eight years.

    http://www.aafp.org/afp/20050401/tips/21.html

  56. #56 Denice Walter
    November 16, 2009

    @ Andreas Johansson: I was only referring to why someone might have the *impression* that Americans smoke less than Swedes.They don’t.

  57. #57 Serena
    November 16, 2009

    @ Marishka #34
    I deliberately chose the word “supplement” to distinguish it from “drugs”-ie the substances that have been tested for efficacy and safety. What I refer to as “supplements” are those items bought in a health food store or sold over the internet by rather dubious characters. You can quibble over the word “supplement” but I think you know exactly what I mean.

  58. #58 Pablo
    November 16, 2009

    So $3.30 a day x 365 x 8 x 84 = $809,424 to prevent one case of invasive breast cancer – I can guess how HMO actuaries would look at that.

    It depends on how much life it saves. I mentioned before that I heard recently that the going rate on the value of life right now is $50K per year of life saved. So if preventing one case of invasive breast cancer would increase that life by 16 years, then this would be a cost-effective treatment.

    However, I don’t know what the average cost of life span is for breast cancer. Given the life expectancy of women is nearing 80, that means breast cancer would have to be terminal by about 64.

  59. #59 Kemist
    November 16, 2009

    @hibob:

    the NNT, the Number of people you Need to Treat for one person being prevented developping the illness, is highly dependant on who exactly you decide to treat.

    What some commenters were talking about, like Margaret @44, is that it would become practical when we have a decent breast cancer risk marker at least as good as LDL – that is what would bring the NNT to more reasonable levels.

    Also, it has been shown in many papers that HT beyond 5 years shows almost no benefit. The reason for this is that an ill-understood mechanism modifies the estrogen receptor (there’s probably an upregulation in a kinase or two) to make the SERM or anti-estrogen act as an estrogen – that effectively makes your drug a risk factor rather than a preventative. Curiously, that same 5 year limit is also what is observed for the cardiovascular benefits of traditional (E2 + Prog/premarin) HRT.

    Additionally, if ever a market for a breast cancer preventative came to exist, there are better drug candidates than ralox, which was specifically developped for cancer treatment rather than prevention, ie to get a much tighter control on the suppression of estrogen stimulation. Its positive effects on bone density were an added bonus, not something the developpers of the drug strived for. The perfect profile for a preventative drug is not the same as that of a curative drug, for obvious reasons.

  60. #60 Chris
    November 16, 2009

    Also, it should be noted that it was stated in the study hibob linked to that only women who were being treated for osteoporosis were eligible. Since Orac mentioned that raloxifene is used to treat osteoporosis, it might be that the cancer protection was secondary to preventing fractures (especially broken hips) in women.

  61. #61 Kemist
    November 16, 2009

    As far as anti cancer effects on vegetables, I seemed to think that I read some abstracts along the way wherein some of the things you get in a vegetable rich diet (i.e., leutolin, flavonoids) inhibit things that tumors use to grow (i.e., VEGF).

    VEGF = Vascular Endothelial Growth Factor, is not something that makes tumors grow, but rather something that some tumors (and your body !) use to build themselves new blood vessels.

    And it is very far from a panacea. VEGF antagonists were rather disapointing when tried as cancer treatment on humans – they had no effect on their own, only in synergy with other chemotherapy agents.

    I would not put much money on any real effect on cancer prevention either. I’m thinking that way because, as a tumor develops, it does not need VEGF before being big enough to become a problem – at which point it will be established and noticed as a tumor.

    VEGF antagonists showed such spectacular success on mice grafted with tumors precisely because such tumors are highly dependant on the creation of new blood vessels to “take”, being deposited as a mass of a few million cells.

    Naturally developping tumors are not that dependant, at least at their beginnings.

    For me the VEGF antagonist story, just like the story of the rats whose “immune system beat cancer”, is a warning to life scientists to beware of the limits of their models.

    I do not think you get significant anti-VEGF activity from vegetables. If you were, you might be experiencing their side-effects as well. VEGF is necessary to rebuild blood vessels after an injury, for example. Its release is also stimulated when you exercise, to increase your oxygenation capacity and vascularize your muscles.

    Their side-effect are relatively mild as chemo agents, but you would not appreciate them in a preventative.

  62. #62 adina
    November 17, 2009

    I found Kolata’s discussion of hormone replacement therapy to superficial at best, and in many ways inaccurate. If you look at various pooled analyses of HRT (I’ve seen a great talk by Dr. Daniel Mishell about the various level of evidence for the risks and benefits that seem to be associated with HRT). Yes, combined progesterone and estrogen replacement therapy seems to increase your risk of breast cancer. However, estrogen alone does not. Estrogen alone increases your risk of uterine cancer, but the combined hormonal contraceptives do not. Both estrogen and combined hormones reduce your risk of ovarian and quite possibly colorectal cancers. Even women who took estrogen and later developed uterine cancer had a lower overall mortality rate than women who did not take estrogen and did NOT develop uterine cancer, which is a truly shocking finding. And, of course, there seems to be in a difference in cancer rates (as well as thromboembolisms, and other side effects of HRTs) depending on the route of administration, with the estrogen transdermal patch seemingly more favorable than the estrogen pill, due to the “first pass effect” of the latter. And let’s not forget that cancer isn’t our only fear. I fear Alzheimer’s Disease and osteoporosis as well, and the risk of both are decreased by use of HRTs. Even according the WHI study, women ages 50-59 on estrogen had a significantly significant decrease in the rate of MIs, compared to women on placebo controls. There’s a lot more to the story, and Gina Kolata omits some very important findings.

  63. #63 Dianne
    November 17, 2009

    “Cancer” is not a disease, but many diseases arising from many different organs with many different biological behaviors. There is no drug that can prevent “cancer.”

    Even worse, drugs which prevent one cancer may increase the risk of another. Tamoxifen is the prime example of that: there is an increased risk of uterine cancer with tamoxifen as well as a decreased risk of breast cancer. The increased risk of uterine cancer is quite low compared to the decreased risk of breast cancer so it makes sense to use tamoxifen for secondary prevention or for primary prevention in high risk groups, but for average or low risk patients it’s not so good.

    Looking for a drug to prevent cancer is a bit like looking for a drug to prevent infectious disease. Just not going to happen. However, there are a number of interventions which can reduce the risk of certain cancers, some of which are underutilized. Colonoscopy can reduce the risk of colon cancer but only 50-70% of eligible patients have ever had a colonoscopy and many fewer have had one within the recommended 10-year window. The HPV vaccine could reduce the incidence of cervical, head and neck, anal, and penile cancers significantly if it is used widely. And with a single application. Isn’t this the holy grail of prevention that the alties say they’re seeking?

  64. #64 LK PhD
    November 17, 2009

    Looks like you may want to re-visit this issue, after yesterday’s revised guidelines on breast cancer screening. The backlash has been stunning – it amazes me how many doctors rebel against evidence-based medicine.

  65. #65 Kemist
    November 17, 2009

    @adina

    I also find it curious that the benefits of traditional HRT are being swept under the rug these days, essentially because of a PR problem. And it’s that same attitude that is being a nuisance to SERMs, be it in cancer treatment or prevention.

    For some reason, people are much more afraid of cancer than they are of coronary disease, diabetes, osteoporosis and Alzheimer’s, despite the fact that all these illnesses result in as much, if not more mortality and morbidity than cancer does. Cadiovacular problems, on average, kill people younger than cancer – so it’s not really surprising to me that women on estrogen therapy have less mortality, even with cancer, than controls.

    However, most people don’t want to hear the reality of medicine (and of life in general), that an intervention is always an exchange of risk factors, not an elimination of risks. They want to see “good” things and “bad” things. It confuses them when you tell them, “yes, but” – and they will often turn to someone who will affect complete confidence, even if that person is lying.

    However, the thing with SERMs (Selective Estrogen Receptor Modulators), is that you can tailor them to have effects in whatever tissues you want. In essence, you can have a substitute for estrogen that has the cardioprotective, brain protective and bone protective effects of estrogen, without much stimulation of breast or endometrial tissue. You can have a drug that has a much better profile than estrogen does, to be given in a carefully chosen age window.

    There are no SERMs presently on the market (ralox and tamox are adjuvant curative anti-cancer drugs, designed to suppress estrogen activity, not mimic it) which have been designed for preventative purpose, but there could be – if ever a market could be developped for it.

  66. #66 leigh
    November 17, 2009

    the Lappe et al vitamin D study had several major flaws, not the least of which was a “negative control” group with a significantly higher rate of cancer incidence than observed in far larger population studies.

    i stand by my assertion. taking an in vitro result or a correlational study and attempting to extrapolate it to clinical practice is missing several large and important logical steps. until we’ve got data, there is no basis for stating that low serum vitamin D *causes* cancer or that vitamin D supplementation *prevents* cancer.

  67. #67 Nusret
    November 18, 2009

    i stand by my assertion. taking an in vitro result or a correlational study and attempting to extrapolate it to clinical practice is missing several large and important logical steps. until we’ve got data, there is no basis for stating that low serum vitamin D *causes* cancer or that vitamin D supplementation *prevents* cancer.

    Posted by: leigh ‘ yes.

  68. #68 red rabbit
    November 18, 2009

    @Eric 14 and @Diane 58:

    Actually, there has been a significant amount of study looking at diet and disease, in particular cross-culturally.

    The one that comes immediately to mind is the rate of gastric cancer in Japan as compared with North America. The studies first demonstrated that first generation immigrants to NA from Japan maintained their elevated gastric cancer rates; the second generation had rates comparable to the native population. Diet was thought to be the link. However, research did not bear this out.

    This research eventually led to the discovery of the bacterium Helicobacter pylori, now understood to be the causative agent for a significant number of gastric ulcers and much of gastric cancer.

    This is not to say diet is irrelevant: it’s not. It’s just not the ONLY thing we need to research.

  69. #69 Prometheus
    November 18, 2009

    Darren Scott comments (#51):

    “It’s wonderful to know that some ethical folks have put in a tireless effort and I can now return to pouring cheerios, batter, cheese, milk, ice-cream and soda down my throat, together with my 5 anti-cancer chemicals. The ‘WAR’ on cancer is won, folks!”

    It’s a straw man, but an amusing straw man. This comment (which may be an attempt at humor – it’s so hard to tell) nicely illustrates the “false dichotomy” that Orac refers to. In the event that Darren is truly confused about the point of the post, let me try to explain – in nice, simple bullet points.

    [1] Even if diet were eventually found to be completely irrelevant to cancer, that doesn’t mean that diet is irrelevant to all disease. The dietary habits Darren describes would put him at risk (in all liklihood) for coronary artery disease, obesity, type II diabetes etc.

    [2] Even if certain dietary habits or items are found to increase the risk of cancer (which I’m pretty sure has been documented), that does not make it true that having a “healthy” diet (whatever that might mean) will prevent cancer (beyond removing the increased risk of known cancer-related dietary habits/items).

    [3] The data so far – which are admittedly limited – do not support the claim that a “healthy” diet can reduce cancer risk below what you might experience eating a “typical Western” diet.

    [4] Of the few studies that looked at the influence of specific dietary changes on specific cancer risks, most have shown little impact. A few – selenium, for example – have shown an increase in risk of specific cancers. People often say that eating a “healthy” diet and taking “supplements” is harmless – “it can’t hurt and it might help” is what I often hear. The take-home message about selenium (and some other “supplements” that have been studied) is that they can hurt – they might increase your risk of cancer. [“You often meet your destiny on the road you take to avoid it.”]

    [5] The “typical Western” diet is a mythological creature. Given the wide variety of diets eaten by people in the so-called “Western” countries, anyone talking about how “unhealthy” (or “healthy”) the “Western” diet is can be assumed to be speaking nonsense. For example, people in the UK (a “Western” country) eat very differently from people in France (also “Western”) and Sweden (ditto).

    For that matter, people on the West and East coasts of the US eat differently from those in the MidWest and even people in the same geographic area eat radically different diets because of differences in ethnicity, availability, socio-economic group, fad and culture (and probably another dozen factors I haven’t included).

    It would be wonderful if eating a “healthy” diet could protect us from “cancer”, but biology is rarely that simple. Many cancers are caused by viruses, some by UV light, others by genetic mutations (either acquired or inherited). At best, diet can only affect a few of these causes.

    Prometheus

  70. #70 Joseph C.
    November 18, 2009

    It would be wonderful if eating a “healthy” diet could protect us from “cancer”, but biology is rarely that simple. Many cancers are caused by viruses, some by UV light, others by genetic mutations (either acquired or inherited). At best, diet can only affect a few of these causes.

    This is a real bummer, dude. I’m going to go back to reading Mike Adams now. He tells me what I want to hear.

  71. #71 Redblues
    November 18, 2009

    I can’t speak for all women, but I can tell you why I do not take Tamoxifen – side effects. Almost every woman I know who took it (and I know a lot) suffered horrible side effects. I was diagnosed with invasive DCIS HER2+ and ER+ at the age of 39 (five years ago). I was a life-long health food eating athlete with no risk factors other than being female and never having had children. I had lumpectomy, ACT chemo, radiation and Herceptin. I felt great during chemo, except for the continual 24 hour a day hot flashes. I was not in menopause at diagnosis and am not now, although chemo put me in temporary menopause, with the resulting horrible hot flashes. Even bald, in the dead of a New England winter, they were ghastly. I was never comfortable. I can’t imagine what I would have done if it had been summer. I refused Tamoxifen because I did not want to go through that again, along with mood swings, vaginal dryness, etc. It is counter-intuitive to take medicine that makes me feel bad on the chance that it may prevent more breast cancer. Perhaps I will reconsider, but I doubt it. One hot flash and all the pills would go in the trash.

  72. #72 AD
    November 19, 2009

    Gary Taubes has some interesting things to say about diet and cancer in “Good Calories, Bad Calories.”

    And this post on the Okinawan diet suggests that the conventional wisdom might be a little off: “Okinawan culture not only embraces one of the most heart-healthy diets (high seafood, animal meat, milk, eggs, saturated fats, high minerals and low carb) but also a very physically active lifestyle.”

    http://drbganimalpharm.blogspot.com/search/label/Okinawan

    If eating more fruits, vegetables, and fiber doesn’t reduce cancer, couldn’t it just mean that we’re asking the wrong questions, and running the wrong experiments, rather than that dietary composition doesn’t matter?

  73. #73 Sekhar
    November 19, 2009

    I stumbled on your blog today and like the perspective a lot. I was struck, though, that you accepted Kolata’s statement on the value of finasteride without question. The PCPT trial (randomized, double-blind, nearly 19,000 men), published in NEJM in 2003, is the most definitive to date, which indeed found a significant prostate cancer reduction in the finasteride group (18.4% VS 24.4%), but, very disturbingly, an increase in Gleason grades 7-10 (6.4% vs 5.1%):
    http://www.nytimes.com/2003/06/25/us/mixed-results-for-drug-used-to-prevent-prostate-cancer.html
    http://content.nejm.org/cgi/content/full/349/3/297
    http://content.nejm.org/cgi/content/full/349/3/215
    The conclusion in the NEJM abstract: “Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.” Merck was disappointed since they had hoped to expand their market from men with enlarged prostates (BPH) to all middle-aged men. They did a follow-up with some very complex mathematical modeling that claimed to show that the higher incidence of more serious cancer might have been due to better detection (Cancer Prevention Research 2008, a brand-new journal). But this was all post-hoc analysis. No other clinical trial has been completed till now; a trial with dutasteride (REDUCE) is nearing completion. So, Kolata’s statement about finasteride (or dutasteride) is not supported by clinical trials.

  74. #74 Ballack
    November 20, 2009

    I stumbled on your blog today and like the perspective a lot. I was struck, though, that you accepted Kolata’s statement on the value of finasteride without question. The PCPT trial (randomized, double-blind, nearly 19,000 men), published in NEJM in 2003, is the most definitive to date, which indeed found a significant prostate cancer reduction in the finasteride group (18.4% VS 24.4%), but, very disturbingly, an increase in Gleason grades 7-10 (6.4% vs 5.1%):
    http://www.nytimes.com/2003/06/25/us/mixed-results-for-drug-used-to-prevent-prostate-cancer.html
    http://content.nejm.org/cgi/content/full/349/3/297
    http://content.nejm.org/cgi/content/full/349/3/215
    The conclusion in the NEJM abstract: “Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.” Merck was disappointed since they had hoped to expand their market from men with enlarged prostates (BPH) to all middle-aged men. They did a follow-up with some very complex mathematical modeling that claimed to show that the higher incidence of more serious cancer might have been due to better detection (Cancer Prevention Research 2008, a brand-new journal). But this was all post-hoc analysis. No other clinical trial has been completed till now; a trial with dutasteride (REDUCE) is nearing completion. So, Kolata’s statement about finasteride (or dutasteride) is not supported by clinical trials.

  75. #75 Mo
    November 20, 2009

    Katie @1:

    I saw Kolata on The Colbert Report and was very impressed to learn that she has enough of a sense of humor to have the Pina Colada song as her cellphone ring tone.

  76. #76 Kismet
    November 23, 2009

    @Nusret, leigh you forgot the evidence from preclinical animal models, but *how else* do you think science works? We take in vitro, preclinical and observational data and do the damn phase I & II studies and more. There’s no magic involved. We wouldn’t do those human studies if the hypothesis wasn’t plausible to some degree.
    The type of black & white thinking you practise is unfortunate: As you must know in the real world, there are odds inbetween 0 and 100%. Right now the totality of evidence suggests that low vitamin D level ain’t beneficial to one’s survival.

  77. #77 Old Ruby
    December 11, 2009

    I am a bit out of my depth here among the academics in this blog, but just want to express the following. I have been a vegetarian for 38 years, I pay particular attention that I get sufficient protein and nutrients and do not supplement my diet with anything else (ie supplemental nutrients, vitamin pills etc). I drink 3 litres of fluid each day (mainly water, but also some vegetable juices), eat fruits, veges, nuts, etc. I exercise, mainly weight bearing exercise, practice yoga, live a happy harmonious life, get my blood tested every 6 months (as suggested by my doc cos I am 52 and a vegetarian), have mammograms, ultrasounds, pap smears regularly etc etc etc. I DO ALL THE THINGS THAT ARE SUPPOSE TO PREVENT BREAST CANCER. I have no history of it in my family but I have just had my tits chopped off and all nodes in my right arm removed. So, in my opinion diet does not have anything to do with whether you get it or you dont. What diet MAY be able to do (and I emphasise ‘may’) is perhaps help you to heal more quickly from illness and disease. I had no bruising and minimal pain after my op, and my skin is stretching extremely well with the skin expanders. I was out of hospital 20 hours after the op and cleaning the house 2 days after. Could be diet, or could just be luck.

    My surgeon has suggested 5 years of tamoxifen. As there have been no long-term studies conducted on women with oestrogen related bc using natural methods to combat this disease, I would be a ninny not to adhere to my surgeon’s recommendation even though I am a staunch ‘health nut’.

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