Professor Finlay Macrae at The Royal Melbourne Hospital is currently leading a trial that aims to investigate the preventative effects of red wine, containing resveratrol, on the development and progression of bowel cancer. Interview with Dr Norman Swan.
Transcript
Norman Swan: Let's stay in the neighbourhood and go to the head—or should it be the bottom—of colorectal medicine at the Royal Melbourne Hospital.
Professor Finlay Macrae is a leading authority on bowel cancer prevention and we've had him on the Health Report before talking about aspirin. He's now starting another prevention trial, this time into a substance called Resveratrol which comes from wine, and which I'd only heard of before in relation to slowing down ageing and life extension.
Finlay Macrae: Yes, there is a literature on that, mostly derived from animal studies and some invitro work.
Norman Swan: What exactly is it?
Finlay Macrae: It's a polyphenolic compound.
Norman Swan: It's also a polysyllabic word. What does it mean?
Finlay Macrae: Well, it's a chemical compound inherent in fruits and particularly grapes, and it's thought to be one of the agents from grapes that has health benefits. Resveratrol is the most prominent phenolic compound in grapes.
Norman Swan: And it's an antioxidant.
Finlay Macrae: Yes, it has antioxidant effects but it has a range of other effects that are perhaps more relevant in that it may have anticarcinogenic effects. For example, it slows down proliferating cells and promotes apoptosis, or programmed cell death, which is one of the body's mechanisms to delete early malignancies developing in the body.
Norman Swan: Essentially the body's cleaning-out process, and some people think that cancer is a failure of that programmed cell death and cells that should have died keep on living.
Finlay Macrae: That's correct.
Norman Swan: And what makes you want to do a trial of this? Has it been studied in other areas and shown promise?
Finlay Macrae: Well, it's been studied a lot invivo, in cell systems, including colon cancer cell lines. It reduces the activity of the COX enzymes which is the mechanism by which aspirin works to protect against cancer as well. And of course there's epidemiological evidence because the polyphenolic compounds of which Resveratrol, as I mentioned, is a predominant one is very much part of the southern Mediterranean diet and we know that the southern Mediterranean diet has a profile of protection against bowel cancer. Resveratrol might be contributing to that southern Mediterranean dietary protective effect.
Norman Swan: So you're planning this trial—what side effects are known from Resveratrol, because nothing is free of side effects.
Finlay Macrae: No, well, it's pretty safe. Of course in drawing the substance from an alcoholic beverage (wine) we've been certainly concerned about that. So we've actually developed a Resveratrol derived from Australian grapes which is de-alcoholised.
Norman Swan: So you can drive and be on this trial.
Finlay Macrae: Yes. And apart from that, it's pretty widely used by the health food industry and has a status of generally safe. So there's not much that we can really pinpoint with respect to risk, although you're quite right in saying there's always some reservation about that with time passing, but it's not as if it's a new compound, it's been used for a long time.
To determine effectiveness for prevention of bowel cancer, and the most solid end-point of course is cancer, and that's perhaps what everybody would think a trial might direct, but that would be a vast trial involving lots of people and millions of dollars.
Norman Swan: So what you're getting to is that you're doing a trial which is not looking at cancer but maybe somewhere along the path to cancer.
Finlay Macrae: Along the line, yes. So adenomas, or benign polyps, are another end-point that's being used quite commonly, but we've taken a step even earlier than that, and what we're looking at is the landscape, the molecular landscape if you like, of the lining of the bowel, to see if we can shift a range of molecular characteristics that we know are associated with either protection or promotion of malignancy. We're looking to shift that into a landscape that is much more protective, with the use of Resveratrol.
Norman Swan: So to keep with the landscape metaphor, you're tilling the soil a little bit and trying to change the chemical composition of the soils, it grows a more healthy tissue surrounding the bowel.
Finlay Macrae: Yes, and in particular a soil which is not associated with or support the development of tumours.
Norman Swan: So people are going to go on to Resveratrol or the placebo. And are you looking for people who are at particular risk of bowel cancer, or just people off the street?
Finlay Macrae: No, we're starting with a group that are already at high risk who have a profile of this landscape which is associated with tumour development, and that would in principle be people who'd had previous polyps or cancers themselves, or people who've got a first-degree relative with bowel cancer. They're our major target groups because they already have a background landscape that lends itself to being protected with an agent such as this. So they're the group: first-degree relatives with bowel cancer or people that have had bowel cancer or polyps themselves.
Norman Swan: How long will you be on the trial?
Finlay Macrae: Six weeks.
Norman Swan: So you're expecting to see those changes, and if you've got those changes how confident would you be that they will result in a lower risk of cancer in the long run?
Finlay Macrae: There's some leap in scientific thinking between changing the landscape and actually reducing the risk of cancer. But the thesis is that if we change the landscape into a protective-looking one, this provides a little bit more evidence, quite important evidence, this is the first evidence in humans that the compound is active in terms of its potential to be anticarcinogenic.
Norman Swan: And at the moment really all people have is aspirin.
Finlay Macrae: Aspirin (we've spoken about that before, Norman, of course) is the lead boy on the block at the moment.
Norman Swan: Or girl…
Finlay Macrae: Or girl, yes. But non-steroidal anti-inflammatory drugs of other types are protective, the usual ones people use for arthritis, a lot of them are protective of various types of those agents.
Norman Swan: If you take aspirin what sort of a reduction in risk do you get? I suppose it depends on the person, but on average?
Finlay Macrae: Fifty per cent.
Norman Swan: So it's a pretty significant reduction. And would you be expecting the same order of magnitude with Resveratrol, or greater?
Finlay Macrae: I think we'd be looking hopefully to get to that sort of effect, 50% reduction.
Norman Swan: So just before we get on to where people can go if they want to take part in this trial…is it only people in Melbourne, or are you looking for people nationally?
Finlay Macrae: No, only in Victoria.
Norman Swan: How do people get in contact with you if they want to take part in the trial, if they fit the bill?
Finlay Macrae: They're best to contact our research team, Virginia or Brooke, on 
03 9342 8995 . That's our research office in the Royal Melbourne Hospital.
Norman Swan: And we'll have the email contact on our website. Professor Finlay Macrae is head of colorectal medicine and genetics at the Royal Melbourne Hospital.
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