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Podcast Interview Transcript, April 2010


Adam Weiss Welcome to the JNCI podcast, a production of the Journal of the National Cancer Institute. I’m Adam Weiss. Eat your vegetables. We’ve all been told that fruits and vegetables are good for us. They’re full of important nutrients, low in fat and calorie, and they can even fight disease. For the last couple of decades, scientists have even agreed that that an apple a day keeps the doctor way is true for cancer, for the number of studies showing that eating more fruits and vegetables is strongly associated with a reduced risk of many different cancers. However, these studies haven’t always agreed on how big a benefit you actually get from scooping a little more broccoli onto your plate. So a group of researchers looked at data from EPIC, the European Prospective and Investigation into Cancer and Nutrition, to see if this study of over half a million people could give a clearer picture of how a diet with more fruits and vegetables is related to cancer. They published their results in Issue 8 of JNCI, and to talk about what they found, I have Dr. Regina Ziegler on the phone with me from Bethesda, Maryland. Dr. Zeigler is an epidemiologist and a senior investigator at the National Cancer Institute. And while she wasn’t involved in the work directly, she studies how lifestyle affects cancer risk so she should be able to give us insight into what this new study means. Welcome Dr. Ziegler.

Regina Ziegler: Thank you.
Adam Weiss: Now before we get to the results, I wanted to find out how they were able to get so much data. These researchers looked at hundreds of thousands of people, but they didn’t actually go out and watch these people eat. This information came from a long-term study called EPIC. Can you tell us what that is?
Regina Ziegler: EPIC is a prospective study in diet and cancer that was conducted in ten western European countries. It took advantage of the wide variation in vegetable and fruit intake across Europe. Basically what was done, cohorts of individuals were identified in the various countries. Diet was collected at baseline in great detail. The individuals were followed up for a number of years, I think on the average of eight years, cancer morbidity and mortality was collected, analyses were conducted to see how the diets, specifically the fruit and vegetable intake in those individuals that did develop cancer, differed from the fruit and vegetable intake in those individuals that did not develop cancer. That’s what a cohort study is. Not only did this cohort collect very detailed dietary information at baseline, it also collected information about the accepted risk factors for most of the major cancers, information about alcohol use, about smoking, about reproductive and menstrual factors, which might be relevant to breast cancer, information about physical activity, so that

these parameters could also be entered into the analysis that would enable the investigators to determine whether the associations that they saw were really due to dietary factors, in this case vegetables and fruit, or due to other partially associated determinates of cancer risk. One very important thing about EPIC is that they collected diet very carefully, with well thought out interviews with a lot of detail. And the dietary assessment that went into the study is among the strongest that has been used in a cohort.
Adam Weiss: So these researchers looked at this very well collected data and found something that seems to come pretty close to contradicting what people have been saying about cancer and vegetables for over a decade. There was a study back in 1997 that showed that fruits and veggies were associated with less cancer, right?
Regina Ziegler: Well actually, one can even go further back than 1997 if-- throughout the 90s, most scientists in this field would have said that the most persuasive association between any dietary factor and cancer was the protective affect of fruits and vegetables. It was widely believed to be a strong association, and a potentially causal association, and over time the evidence for this hypothesis has diminished. And this particular study, which is very large, shows that consuming an additional two servings a day of fruits and vegetables is associated with

a very modest reduction in risk of cancer, actually only about a three percent decrease in risk of all cancers.
Adam Weiss: So I guess the affect seems to be small in the overall group of half a million people. But the paper does say that people with those other risk factors you talked about, so smokers or heavy drinkers, got a bigger benefit. Does that mean that vegetables help some people and not others?
Regina Ziegler: Well, just going back, even though the association was modest, it was statistically significant, so the authors felt that they could rule out the possibility of chance for this association. But you’re asking me about what was seen in subgroups. Maybe we should try to understand why they even chose to look at subgroups. And if you look at the history of research on fruits and vegetables and cancer, one concern has always been that there’s uncontrolled confounding. All that that means is that the people who are eating more fruits and vegetables will tend to drink less, will tend to smoke less. We know that drinking and smoking cause a variety of cancers and so there’ll be an appearance of a protective affect of fruits and vegetables simply because the high fruit and vegetable consumers have less adverse lifestyles that we know to be linked to other cancers.
Adam Weiss: But looking at the paper, the researchers found that higher fruit and vegetable intake in smokers and drinkers

was specifically associated with lower risk of the cancers that you getfrom smoking and drinking. Doesn’t seem to me like this confounding effect that gives you results that aren’t really there would explain that.
Regina Ziegler: No, that’s true. The authors did find stronger associations in those cancers associated with smoking and associated with drinking. In the paper they said there are two ways to explain their findings, and one is that you have uncontrolled confounding in the heavy drinkers. And the reason you’re seeing a really strong protective effect in the heavy drinkers is that the heavy drinkers, they’re eating less fruits and vegetables. In other words, even among heavy drinkers there’s variation. And the heaviest of the heavy drinkers will eat fewer fruits and vegetables than the lighter of the heavy drinkers. But there’s another very interesting explanation that may be true. Drinking has been known to interfere with the utilization of folate. And folate is critical to DNA repair and DNA synthesis integrity. Many people have hypothesized that folate and one carbon metabolism play a very important role in carcinogenesis, and if alcohol interferes with the bioavailability of folate and folate is found in fruits and vegetables, we know that, then it could be that the very noticeable protective effect we’ve found in fruits and vegetables in the heavy drinkers is due to the fact that the folate in fruits and vegetables is particularly

critical in people who drink a lot. Either explanation could explain the data. We don’t really know what the answer is.
Adam Weiss: Along those lines, when I was reading the paper, I kept thinking about overall amounts of food. You know, if you’re eating two or more servings of fruits and vegetables, it doesn’t mean you’re eating more overall. You’re eating that banana instead of something else. Could it be that there’s something else that these people are eating that causes cancer, rather than the vegetables preventing it?
Regina Ziegler: That’s a possibility. There are many mechanisms that can be proposed for why fruits and vegetables are protective. And some of the mechanisms could pertain to what’s in the fruits and vegetables themselves, like antioxidants and antiproliferative agents. But it could also be due to the fact that when you eat more fruits and vegetables you eat less fat and you eat less meat, and a number of studies have indicated that high intake of meat, particularly meat that’s cooked at high temperatures, may be associated with increased risk of cancer. So it could be the fruits and vegetables are themselves not protective, but they’re protective because of the way they affect other things being consumed. So that’s a possibility. But in the grand scheme of things we’re talking about a really small association here, and so I wonder whether we should worry a lot about trying to understand what the mchamism is if it's such

a modest association.
Adam Weiss: So should we be saying that people don’t need to eat fruits and vegetables anymore? I mean we know that they do a lot of other good things even if fighting cancer might not be one of them.
Regina Ziegler:First of all, what I was trying to say is that vegetables and fruits were the hottest protective agent in the cancer universe, maybe 15 years ago. Tons of money was poured into understanding what the underlying mechanism is. The evidence that fruits and vegetables are highly protective for cancer has weakened and weakened and weakened over the last 15 years. So given limited resources I think it may be more important to understand more about obesity, which is associated with a number of cancers, how to get people to give up smoking, other things that we know are strongly linked to cancers, rather than trying to understand the mechanisms underlying the protective effects of fruits and vegetables. But you made a good point, and in fact, Dr. Willard, [ph?] in his editorial, makes the point also that even though the evidence of fruits and vegetables reduce the risk of cancer is modest based on this article, there’s increasing evidence that a diet high in vegetables and fruits reduces the risk of heart disease and stroke. More people in the United States and western Europe die of heart disease and stroke than die of cancer. And so if fruits and vegetables really reduce the risk of those diseases, then w

should increase them in the diet. And as other than for the relationship with cardiovascular disease and cerebral vascular disease not only from observational studies but I believe from some trials. So we should encourage more consumption of vegetables and fruits. In addition, I think many people would argue that eating more vegetables and fruits will help someone to lose weight, and all the newspapers are pointing at that at the present time there’s an epidemic of obesity in the United States. It starts young and continues and gets worse as people age. So even though fruits and vegetables may not reduce the risk of cancer, if they can help someone not put on excess weight, or take off excess weight, then there’s a very good argument for keeping them in the diet.
Adam Weiss: And even in this case there was a statistically significant effect on cancer, even if it’s small, and it looks like it gets bigger the Regina Ziegler: Right. In this analysis the authors focused on the protective effect of an additional 200 grams of vegetables a day, which is about two servings. However, within the populations that they studied, there’s almost a fivefold range in servings of vegetables and fruits per day. In other words, people can incorporate more vegetables or fruits in their diet than just an additional two. And if you look at their data, again, the data from the same study, and you compare people in the top quintile

of vegetable and fruit intake relative to the bottom quintile of vegetable and fruit intake, just looking at their data it looks like the people in the top quintile had over six servings of vegetables and fruits per day, and those in the bottom quintile had on the average maybe one to two servings of vegetables and fruit per day. When you look at it this way, those in the top quintile had 11 percent reduction in risk relative to those in the bottom quintile. So it may be by just focusing in on two servings a day they minimized the impact of increasing vegetable and fruit intake. The other point that was made is that in this analysis, vegetable and fruit intake was measured at one point in time and it was measured during adult life. There’s increasing evidence that certain types of cancers are really started very early, even though they aren’t really diagnosed ‘til later in adult life.
Adam Weiss: So for a number of reasons, even if cancer isn’t as big a one as we thought, for most people you should still eat your vegetables.
Regina Ziegler: Right. And all the mothers who told their children to eat fruits and vegetables as I did, we didn’t mislead our kids. It’s still okay.
Adam Weiss: All right then, I will keep that in mind. Thank you very much for talking with me about this.
Regina Ziegler: Thank you.




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