David Kerr, CBE, MD, DSc, FRCP, FMedSci; Peter Boyle, PhD, DSc, FMedSci


June 08, 2015

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David Kerr, CBE, MD, DSc, FRCP, FMedSci: Hello. I'm David Kerr, professor of cancer medicine at the University of Oxford in the United Kingdom. Welcome to this edition of Medscape Oncology Insights, where we have an opportunity to report highlights of the 2015 Annual Meeting of the American Society of Clinical Oncology. I'm delighted and pleased to be speaking with my friend and colleague, Professor Peter Boyle, who is chairman of the Institute of Global Public Health at the University of Strathclyde in Lyon Ouest-Ecully, which, of course, is in the south of France.

Peter and I have known each other since childhood. We played football together, we've sweated together, and we've written manuscripts together. And it's a wonderful opportunity to be able to interrogate him a little about the epidemiology of cancer. Peter, welcome.

Peter Boyle, PhD, DSc, FMedSci: Thank you. It's a pleasure to be here.

Alcohol and the Risk for Cancer

Dr Kerr: We always think of you as Sherlock Holmes. You know the epidemiology. You're the detective of cancer. One of the controversies that has beset us recently is about alcohol. I find it confusing. I'm a teetotaler, as you know. Lifelong, never having done it. But is it controversial about alcohol? There is an association between alcohol and a risk of developing cancer.

Dr Boyle: Oh, yes. It has been known for over 120-130 years, quantified since about 1911 in the United Kingdom when the excess of oral cancer and tongue cancer in publicans and people in the drinks industry with access to lots of alcohol came about. Then there were publications about absinthe in France in the 1930s. It's very, very clear.

Dr Kerr: Absinthe makes the heart grow fonder?

Dr Boyle: Something like that, yeah. No, it was eventually banned because there was a huge risk of tongue cancer associated with it. I think we've quantified the risk a lot better now.[1] There's no doubt at all that alcohol, on its own, is a risk factor for liver cancer[2] and breast cancer.[3] We'll come back to the breast cancer later. That would be a good discussion. Alcohol acts on its own but also synergistically with tobacco smoking.[4] For instance, the first major study of it was conducted in the north of France, where there is tremendous production and consumption of calvados, which is an apple-based drink.[5]

Dr Kerr: Apple brandy.

Dr Boyle: Yes. And people with a high consumption of calvados and a high smoking level had a 100-fold risk of developing cancer of the mouth, tongue, and larynx.

Dr Kerr: Sticking with the France story, we were often told about the Mediterranean paradox. Somehow the French drink a lot of red wine and that protects them in some ways. Is that complete nonsense?

Dr Boyle: We never say that anything is complete nonsense, but the studies that have looked at that looked not only at red wine, but also the consumption of foie gras at the same time, which is very French and very regional, from the southwest of France.[6] The studies emanate from there. Why should red wine from Bordeaux be different from red wine from anywhere else? And that has never been proven. The whole concept of a protective effect of red wine against cancer is something that is still in the wind, and people are chasing it. But there is no real evidence to support that.

Dr Kerr: This is fascinating because that sort of evidence compels people like me to say, "Well, there must be some magical chemical ingredient, and if we could discover what it is and we could purify it, then we could have cancer prevention in a tablet." So we spend ages looking at flavonoid aglycones, quercetin, and all the rest of it. They're sort of a false trail, really.

One Pill Makes You Healthy?

Dr Boyle: Yes. I think that if we broaden the discussion to that of chemoprevention, it's a dream that you can live like hell, drink as much as you want, have a terrible lifestyle, and pop a tablet and everything will be okay. Well, that's something that we have not been able to show. Those of us at the International Agency for Research on Cancer did lots and lots and lots of studies with chemoprevention with retinoids and so forth. There was nothing that we were able to show. Nothing. But the one thing that we did show, which was very good, was tamoxifen. You know that tamoxifen given to women without cancer will reduce the risk of developing cancer.[7] That's extraordinarily interesting. It has been approved by the US Food and Drug Administration (FDA) for that use, but nobody uses it.[8,9]

Dr Kerr: Why is that? Is it because there is no drug company behind it? There is nobody pushing it? If the data are so clear—and I remember those data very well; beautifully constructed studies—why is there no attraction? Why hasn't it caught on?

Dr Boyle: That's a good question. No one has really paid a lot of attention to it. In tremendous contrast, Americans pop multivitamin tablets every day. The Institute of Medicine reported 6 years ago that no vitamin had any protective effect against anything. But the American population still pops multivitamins. And kids, as soon as they can walk, are getting the multivitamin tablet. There is no evidence for that. There is no evidence that it does any good. On the other hand, we've got tamoxifen, which does good for women if they start to take it in their mid-40s. But nobody takes it. And why that is? We just don't know.

Yes or No to Vitamin D Supplements?

Dr Kerr: Okay. But I'm going to stick up for vitamin D, so let's arm-wrestle about that. There's a big American story about vitamin D and colorectal cancer. We know the inverse correlation. With low levels of vitamin D, there is a higher chance of getting colorectal cancer. There is some stuff emerging about how patients with cancer who have low levels of vitamin D do less well.[10] They relapse more quickly. So even with vitamin D, do you think there is still a question mark about it?

Dr Boyle: There was a very brilliant review from Philippe Autier[11] that was published in the Lancet Diabetes & Endocrinology last year, which showed very clearly that low vitamin D was a consequence of the disease rather than a cause of the disease. And that created a lot of controversy from the vitamin D lobby. But no one has been able to refute it. This was a complete review of all available studies. It seems that low levels of vitamin D are a consequence of a disease process rather than a cause of the disease process.

Dr Kerr: So for us peely-wally Scots—"peely-wally" meaning pale, pasty—who live in a dark northern European country and don't get out much, we don't see much sun. Shouldn't we be taking vitamin D supplements, you and I?

Dr Boyle: Not at all. Glasgow in the 1930s had an epidemic of rickets, and that's vitamin D deficiency. So they added vitamin D to flour, and the whole rickets issue completely disappeared. But there was a minor epidemic in the early 1980s, a resurgence of rickets. However, it only occurred in the population whose origin was the Indian subcontinent. They were importing their own flour made from crushed peas, and there was no vitamin D added to it, so they weren't getting a vitamin D supplement. There is vitamin D in foods, and I think the levels of vitamin D that people have in the United Kingdom are okay, although no authority has come around and said, "This is the minimum amount of vitamin D you must have every day." No one knows what the optimum levels of vitamin D or its metabolites are.

Life Expectancy vs Healthy Life Expectancy

Dr Kerr: Okay. Back to alcohol. So I'm a complete teetotaler. Should I start drinking a glass of wine a day? Is it a J-shaped survival curve for alcohol? What's safe? Am I in danger by being a complete abstainer?

Dr Boyle: The theory of carcinogenesis suggests that if something causes cancer in one molecule, there is a risk factor for cancer. You don't necessarily need to believe it. We know that sunlight is a carcinogen because excess sunlight causes melanoma, but it's not to say that one ray of sun is a carcinogen. So, obviously, when you look at a lot of lifestyle factors, there is some sort of safe dose or safe limit. Whereas for a pure chemical carcinogen like beta-naphthylamine, there is probably no safe limit. I think we need to revise the theories of carcinogenesis and what one little single exposure can do.

Dr Kerr: What's safe? Forget about my joke about starting to drink. What recommendations would you make, because men and women are a bit different in terms of how they metabolize and distribute alcohol.

Dr Boyle: If you go back to the caveman—

Dr Kerr: Back to Glasgow again.

Dr Boyle: Cavemen, Saturday night. Two cavemen were sitting and talking to each other. They said, "It's very strange. We don't drink alcohol and we don't have cigarettes. We don't have any environmental pollution. All the food that we eat is wholesome and there is no contamination. And yet no one lives past the age of 40." So there are big factors out there. The bottom line is that we're not going to live forever. Life is a sexually transmitted disease that is invariably fatal.

Dr Kerr: You heard it here first, folks: None of us are going to live forever.

Dr Boyle: We want to live longer, of course, but we want to live longer and be healthy. Life expectancy vs healthy life expectancy. We need to concentrate more and more on healthy life expectancy, because we're living to ages where conditions such as dementia and Alzheimer's are very common. We've got to take that into account—the balance between life expectancy and healthy life expectancy.

For life expectancy, we keep moving ahead. It's about 80 years in the European Union at the present time: 78 in men and 82 in women. But healthy life expectancy, which is life expectancy without having a severe disability, doesn't surpass 66 in any one of the populations. It's 66 in Malta, 66 in The Netherlands, and below 65 everywhere else—down to 53 or 54 in some of the Baltic states. That means that in some of the Baltic states, half of the population is out of the workforce at 54 years of age.

Dr Kerr: Right.

Dr Boyle: The European Union has this project, Horizon 2020, and the health aim of it is to increase life expectancy by 2 years.

Dr Kerr: That seems very modest.

Dr Boyle: Healthy life expectancy by 2 years in a population of 370 million people is going to be a huge gain.

Dr Kerr: Yes, a big health economic gain. Better-value healthcare. But does alcohol play a part in this, or should we just have the 2-3 units/day? Where is our sticking point?

Levels of Alcohol Consumption

Dr. Boyle: I think we need to avoid overconsumption. The biggest shock in the past 10 years, which sent ripples of shockwaves through the epidemiologic community, was the final proof that drinking alcohol increased women's risk for breast cancer, even if you take all of the other factors into account.[12]

Dr Kerr: I thought that was a done deal.

Dr Boyle: For every increase of 1 unit of alcohol per day, a woman's risk of breast cancer increases conservatively by 7%.[12]

Dr Kerr: That is a huge difference.

Dr Boyle: So if you get 3 units, it's up by about 25%. And you know that's irrespective of other lifestyle factors. We're getting down to low levels of consumption, and I think we need to be very, very, very careful about how we deal with this. Alcohol is interesting. It's different from cigarettes. There is no gain whatsoever in smoking cigarettes, but low levels of alcohol consumption have an effect in our society. People are more likely to talk, to engage, and to relax a little bit.

Dr Kerr: This is a good thing where you come from?

Dr Boyle: It's a positive thing. Not getting smashed like when we saw those men at Kelvingrove Station—

Dr Kerr: Actually, I'll never forget that. Lying unconscious.

Dr Boyle: We can't get to that stage. The arguments for alcohol are really quite complicated, particularly when you get down to low levels. For alcoholics and those who consume high levels of alcohol, there is no gain. None at all. But taking one glass of wine per day probably has a benefit in some respects, and at very low levels, probably a null effect in our lives.

Dr Kerr: Is there an effect from duration of exposure as well? I guess with alcoholism and chronic liver disease, we see it there. But with the cumulative breast cancer risk, you say that for every 1 unit of alcohol, risk increases by 7%. Is that drinking steadily for 10 years or 20 years?

Dr Boyle: It's generally associated with at least medium-term consumption because the studies tend not to have enough cases. The prospective studies tend not to have enough cases of women who drink. Even after 10 or 15 years of follow-up, you don't exactly know what was going on beforehand. But it seems very consistent. There are about 100 studies that are surprisingly consistent, particularly when you're looking for those very low relative risks.

Should Cancer Survivors Drink Alcohol?

Dr Kerr: You've told us about the risk of developing cancers and the associated cancers. For people who have breast cancer, bowel cancer, or other cancers, does cutting out alcohol make any difference whatsoever to their chances of cancer recurrence? Because doctors like me are starting to get interested in lifestyle prescriptions: stopping smoking, changing diet, exercising more. For patients who have had some primary treatment of their cancer, is there any advice about alcohol?

Dr Boyle: Not really. I think you need to separate cancers such as pancreatic cancer, liver cancer, or bowel duct cancer, which have terrible prognoses. We hope we can do something about that, but they've got terrible prognoses, so there's no reason to believe that you've got to stop smoking, stop drinking, and go exercise every day. It's too late.

Dr Kerr: Okay.

Dr Boyle: The big questions surround the major cancers that now have a very long-term life expectancy. If you have an early breast cancer, you actually have a normal life expectancy now. With colorectal cancer, your guys, the medical oncologists, have made huge progress in the past 10 years. Thank goodness you've been able to do something.

Dr Kerr: Something at last. High five, Peter.

Dr Boyle: We've got these cancers that have a very, very long-term life expectancy. What we need to do is systematically look at how we can improve not just patients' life expectancy, but their healthy life expectancy, and whether roles of diet, physical activity, exercise, and weight reduction have anything to do with it. That's probably an area where we shouldn't put a lot of focus at present time, but it should be a focus.

D. Kerr: Fantastic. It has been a delight speaking to you, Peter. It really has. This has been involving, interesting, and educational. Thanks very much, indeed. And thanks again to our Medscape audience for staying with us. This has been a fascinating talk here in Chicago, and I hope you've enjoyed it. Thanks very much for watching and listening.


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