Field of Science

Alcohol and cancer: should we all stop drinking?

This past week, stories on the front page of many newspapers reported that women who drink alcohol in any amount have a significantly greater risk of cancer, especially breast cancer. “Even moderate drinking affects women's cancer risk” read the headline in The Guardian (London).

Is this true, or is this another case where the media (and the scientists talking to the media) are over-hyping their results? The only way to find out is to read the article reporting these results, carefully, and look at their actual numbers, which I did. What I learned was that the lowest risk of cancer was found in women who drank 3-6 glasses of wine per week. Surprised? Read on.

The news stories said that the risk was greater whether you drank red wine, white wine, or any other kind of alcohol. The journal itself issued a press release titled “Million Women Study Shows Even Moderate Alcohol Consumption Associated with Increased Cancer Risk” and it also quoted an editorial appearing in the same issue, which said that “There is no level of alcohol consumption that can be considered safe.”

Wow. Scary stuff. My wife read the front-page story and decided that same day not to drink a glass of wine with dinner. But what is the real risk here? Should you stop drinking wine?

First, here’s how they reported risk: they computed the increase in relative risk for each additional 10 grams of alcohol per day, where 10 grams is approximately the alcohol contained in 1 glass (125 ml) of wine. (125 ml is exactly 1/6 of a bottle, so if you get 6 glasses from a bottle, you’re having a standard glass.)

The article reported a 12% increase in relative risk of breast cancer from each additional glass of wine per day. (That's true - but read on.) The study involved very large numbers, over 1 million women, which means that this increase was statistically quite significant. But they don’t report the absolute risk – only relative risk. Fortunately the article provides the raw numbers, so I’ve computed absolute risk here.

The women were divided into “non-drinkers”, who reported drinking less than one glass of wine per week (24% of the participants), light drinkers who drank 1-2 glasses per week (29% of the participants), and three other groups based on weekly consumption of alcohol, as I show in the table below. The number of cases of cancer was measured an average of 7.2 years later, so what the study really measured was the likelihood that a woman would get some type of cancer over a 7-year period. The average age of the women at the beginning of the study was 55.

Here are the key numbers from the study:

GroupNumber of womenTotal cancersBreast cancers
Non-drinkers306760174166409
1-2 drinks/week371453 19307 7841
3-6 drinks 29389115183 6642
7-14 drinks24089412838 5672
>14 drinks67292 4031 1816

Now, here is what they didn’t report: absolute risk. As you can see from the table below, the difference in absolute risk of any type of cancer, or of breast cancer, is very, very small for light to moderate drinkers:

Absolute cancer risk in the JNCI study
               Any cancer(%)   breast cancer (%)
Non-drinkers 5.68 2.09
1-2 drinks/week 5.20 2.11
3-6 drinks 5.17 2.26
7-14 drinks 5.33 2.35
>14 drinks 5.99 2.70
Perhaps the first thing to notice is that light drinkers – 1-2 drinks per week – had a LOWER risk of cancer than non-drinkers. Thus it seems that eliminating all alcohol might not be a good idea. The authors of the study, though, had a different theory: they explained that some nondrinkers might have eliminated alcohol due to an existing medical problem, and therefore that this group might be less healthy than the others. Therefore they excluded this group from their analysis, and used the “light drinkers” (1-2 drinks per week) as the baseline group. The increased risk is entirely based on comparisons to this group.

Next, notice that the risk of breast cancer in women who drink 3-6 glasses of wine per week rises from 2.11% to 2.26%. That’s a 7% increase in relative risk, but the absolute risk is very small in either case. Also, the risk from all types of cancer actually decreases, from 5.20% to 5.17%, and in fact this figure (5.17%) represents the lowest overall cancer risk in the study. So it appears that the quote from the editorial above, that “there is no level of alcohol consumption that can be considered safe,” is simply not supported by the data. (The editorial was written by two scientists from NIH, M. Lauer and P. Sorlie.)

Third, let’s look at the risk for women who drink 7-14 glasses of wine per week. This is 1-2 glasses with dinner every night – still fairly moderate. As compared to the very light drinkers, risk of breast cancer increased from 2.11% to 2.35%. That’s an increase in relative risk of 11% – this is what the study reported – but an 11% increase sounds a lot more scary than an 0.24% increase. The overall cancer risk in this group increased by just 0.13%, which even in relative risk is only 2.5%. The reason for the smaller overall cancer risk is that the risk for some cancers actually went down with increasing alcohol consumption.

The article, while generally well written, does make a glaring overstatement in its conclusions, one that the editors and reviewers should never have let stand. It is this: “regular consumption of low to moderate amounts of alcohol by women increases the risk of cancers of the upper aerodigestive tract, rectum, liver, and breast.” That is not correct. The study showed an association between increasing alcohol consumption and cancer, but correlation does not necessarily imply causation. The authors should have written that increasing one’s consumption of alcohol is associated with increased risk – not that it “increases the risk.” They didn’t prove that, nor did they offer a mechanism that would explain it.

So: what the study really found was that the healthiest women drink 1-2 glasses of wine per week, or 3-6 glasses per week, depending on how you read the numbers. Emphasizing relative risk, as the authors and the journal editors did, overstates the real risk. The commentaries also conveniently neglected to point out that nondrinkers were excluded from the analysis.

As for me, I just bought a couple of bottles of wine yesterday. I think I'll open one tonight.

Anti-vaccine pseudoscientist Jay Gordon

After the vaccine court decision (discussed in my last post), there have been predictable reactions from many anti-vaccine activists, some claiming that “more study is needed,” others claiming bias, and of course conspiracy theories. One of the most prominent anti-vaccinationists is Jay Gordon, who is Jenny McCarthy’s kid’s doctor, and who has enjoyed a huge amount of publicity by going on TV repeatedly as the vaccine “skeptic”. He employs a variety of logical fallacies to argue, again and again, that vaccines cause autism. What is also remarkable about this guy is that he protests, over and over, that he is not anti-vaccine.

Come on.

Gordon’s latest act is an article in the Huffington Post, which has been a haven for anti-vaccine nonsense, titled “The Vaccine Court was Wrong.” In this ridiculous article, he trots out the usual arguments. First, he says “they should have insisted on further studies to assist in the decision-making process.” Huh? The courts don’t decide what scientific studies should be done. They review the evidence presented to them. The plaintiffs chose 3 cases from among thousands – the best cases they could find, presumably – and presented their evidence. They failed up and down the line to show that vaccines have any link whatsoever to autism. They also failed to show that thimerosal (the preservative that used to be present in some childhood vaccines) has any link to autism. Furthermore, they failed to show any plausible mechanism for how vaccines might cause autism.

Multiple large epidemiological studies have failed to show any link. But Dr. Jay still insists we need “further studies.”

Next, let’s deal with the question of Jay Gordon’s incompetence as a scientist. In a second recent post (last week) by Gordon, he claimed bluntly:
“Let me state very simply, vaccines can cause autism.”
Gordon provides no evidence for this statement – he just declares it to be true. One of the responses on the HuffPost site got him riled up: a commenter said:
“Dr. Jay is not a scientist…. I see no peer-reviewed publications in his biography, no additional training in biomedical research, and no specific expertise in vaccine science. He has no more credibility in telling you that vaccines are unsafe than I, a computer programmer, do.”
This really got Gordon upset. Here’s his reply:
“Actually, I am a scientist. After high school, I continued my education and trained for twelve years in medical science. Subsequent to that, I have observed thousands of children and families and kept records about their health. That, [blogger id], is science.”
Hang on while I get back on my chair. The inanity of that statement floored me for a minute. Let’s see: if I take courses in anatomy, physiology, etc., can I claim to be a doctor? What about that, Dr. Jay? The problem is, taking medical school courses doesn’t make you a scientist – it exposes you to science, true, but in your case you didn’t seem to learn the methods of science, just the facts (presumably).

But even more misguided is Gordon’s claim that his observations (however numerous) trump controlled epidemiological studies. Scientists know all too well how much bias can affect observations: that’s why we do controlled, blinded studies. Gordon seems to think that his experience overrides any number of scientific studies. This is the antithesis of science. If Gordon understood science (he doesn’t), then he would know that subjective experience and beliefs don’t form a valid basis for conclusions. You can use observations to form hypotheses, but then you must test them. In the case of the autism-vaccine hypothesis, it has been tested, repeatedly, and has failed. Real scientists have accepted these results and moved ahead to try to determine the true causes of autism, instead of clinging to failed hypotheses.

Here I have to give a big shout-out to Orac over at Respectful Insolence for his latest post in which he picks apart Gordon’s arguments decisively, and provides a lesson on why Gordon is not only not a scientist, but is one of the most damaging anti-vaccinationists circulating today.

Finally, Gordon also wrote this week that “private industry is once again duping the FDA, doctors and the public. “ There it is – the conspiracy theory. Not that he has any evidence of this – he doesn’t. In fact, most of the large studies showing no link between vaccines and autism (the ones I’ve read) were publicly funded, and run by scientists who had no financial interest in the outcome. In contrast, Dr. Jay is doing very well financially selling his DVD and books where he warns parents about the dangers of vaccines. In fact, his website is a shameless collection of self-promotional materials (I refuse to post a link here) and advertisements asking you to buy his “must-see DVD” (I’m not making that up) and book. So who’s really making money on this pseudoscience?

One final shout-out to Steven Novella for his clear explanation of some of the sloppy thinking and logical fallacies behind Gordon’s arguments. If only people would read Orac and Novella instead of Gordon!

Special court rules that vaccines are not linked to autism

This story is all over the news - it's on the front page of today's Washington Post, in fact, which I was delighted to see - so I won't say much, but I just wanted to make note of it. It's particularly telling in light of last weekend's news - discussed in my previous blog entry - that Andrew Wakefield falsified some of the data in his 1998 paper claiming that MMR vaccines were linked to autism.

The special "vaccine court" ruled yesterday, in three separate cases, each of which was testing a different strategy for claiming that vaccines cause autism, that there was no evidence that vaccines caused autism in any of the cases. The judges rule against the notion that MMR vaccine causes autism, and against the notion that thimerosal used as a preservative in vaccines causes autism, and against the notion that some combination of vaccines and thimerosal causes autism.

I just wanted to quote one of the judges, George Hastings. Not only did he rule that the vaccine-autism hypothesis was "very wrong," but he also wrote:
"Unfortunately, the Cedillos have been misled by physicians who are guilty, in my view, of gross medical misjudgment."
I'd like to think that any doctor who is telling parents that vaccines might cause autism would read this and then look again at the scientific evidence. One more quote from Judge Hastings:
"...the evidence was overwhelmingly contrary to the petitioners’ contentions. The expert witnesses presented by the respondent were far better qualified, far more experienced, and far more persuasive than the petitioners’ experts, concerning most of the key points. The numerous medical studies concerning these issues, performed by medical scientists worldwide, have come down strongly against the petitioners’ contentions. Considering all of the evidence, I found that the petitioners have failed to demonstrate that thimerosal-containing vaccines can contribute to causing immune dysfunction, or that the MMR vaccine can contribute to causing either autism or gastrointestinal dysfunction."
I hope that these cases, and the publicity today, will reassure many parents that they needn't worry when giving vaccines to their children. The far greater worry is that previously-controlled diseases such as measles will make a comeback, as is already happening.

For more details on the recent ruling and other analysis, I recommend the Holford Watch blog here, and Steven Novella's Neurologica blog entry, here. A good explanation of the vaccine court is here.

Autism, vaccines, and Andrew Wakefield’s fraudulent claims

A new article in the Sunday Times of London by investigative reporter Brian Deer reveals new details about the original study claiming that the MMR vaccine causes autism. This now-infamous study, published in The Lancent by Andrew Wakefield and colleagues in 1998, involved just 12 children, all of whom were autistic. It turned out that the children were all recruited to the study – not a random sample, despite the paper’s claims – by Wakefield and a lawyer whom he partnered with, as part of an effort by Wakefield to build a legal case allowing him to make pots of money by suing vaccine manufacturers. And Wakefield also had filed for a patent on a “safer” vaccine that he was ready to offer as soon as he “proved” that MMR wasn’t safe.

The latest article reveals that Wakefield “changed and misreported results in his research, creating the appearance of a possible link with autism, a Sunday Times investigation has found.” Some of this data was revealed earlier, but Brian Deer has dug deeper and found even more troubling information. Not only were the patients recruited to the study by a lawyer seeking to sue vaccine makers, but the data were manipulated (see the details in this extended article) in ways that seriously altered the findings. Several of the children, for example, showed signs of autism before receiving the vaccine, as was revealed in their medical records. The Lancet study reported that all the children showed the first signs of autism after getting the vaccine. Another example: Wakefield reported on biopsies of the colon for all the children, saying that the biopsies were abnormal. This indicated what he claimed was a new syndrome, where measles particles in the vaccine inflamed the colon, causing a “leaky gut”, through which “toxins” somehow made their way to the brain. Subsequent research has shown no evidence of this, and Wakefield has never identified any specific toxins (nor has anyone else).

Well, it turns out that Wakefield altered the biopsy data too. The paper concluded that 11 of the 12 children had “uniform” intestinal changes that they called “nonspecific colitis”. The hospital pathologists, however, “concluded that they were not uniform but varied and unexceptional.” Wakefield’s team met and reviewed the reports, and decided to stick with their original findings anyway.

Wakefield sees himself as a persecuted hero, or at least that’s what he says. Last summer he compared himself to Vaclav Havel, the playwright and political activist who later became President of the Czech Republic. Orac calls this “the Galileo Gambit” – a tactic where you invoke the name of a famous scientist whose theories were initially rejected, only later to be confirmed, as a defense of your own beliefs. The implication is that you’re just like them – in this case, Wakefield is suggesting that he’s just like Vaclav Havel, who stood up to Communism and repression in his native country.

Sorry, Andrew, you’re no Vaclav Havel – not even close. Havel wasn’t trying to file lawsuits to pad his own pockets. One of the most damning pieces of evidence is a document uncovered by Brian Deer that reveals that in 1996 – two years before the infamous MMR-vaccine paper, Wakefield and his lawyer associated filed documents seeking funds from the UK Legal Aid board for this:
“to seek evidence which will be acceptable in a court of law of the causative connection between either the mumps, measles and rubella vaccine or the measles/rubella vaccine and certain conditions which have been reported with considerable frequency by families who are seeking compensation.”
In other words, Wakefield was looking for evidence that he could use to sue vaccine makers. This is one of the most elementary errors one can make in a scientific study, the confirmation bias problem: you decide in advance what you want to find, and then you interpret all the evidence in a way that supports your pre-conceived notions. In Wakefield’s case, this also conveniently profited his own bank accounts: he earned £435,643 (as reported by Brian Deer) through his work with lawyers.

For 10 years now, scientists and the media have treated Andrew Wakefield with respect. He’s done countless interviews and presented himself in the media as he likes to be seen, and meanwhile scientists have spent millions of dollars and years of effort trying to replicate his findings. All the scientific results have shown the same thing: that there is no link between the MMR vaccine and autism. These years of research could have been devoted to productive research on autism, trying to find the real causes, rather than chasing false hypotheses.

There are only two explanations I can think of for Wakefield’s continuing insistence that he’s right: either he’s incompetent or he’s a fraud. ( Orac calls him an "antivaccination loon" - a bit strong, but justified. David Gorski at Science-based medicine calls him a scientific fraud.) I’ve seen his interviews and he really seems to believe what he’s saying, so my conclusion is that he’s incompetent. Rather than treat Wakefield with respect, we all (journalists included!) show be showing outrage over the damage he’s causing to public health. Because there’s no mistake about that: vaccination rates have fallen, many children have gotten sick as a result, and some children have died. That’s a very real cost, and a tragic one.

Creationism in the journal Proteomics

Last year, a controversial paper on the mitochondrion, including a claim that amounted to "God did it" (created life), almost slipped into the journal Proteomics. I say "almost" because the article appeared online before print, and then caused such a furor that the journal withdrew it from their website and the print version never appeared.

I wrote a brief account of the whole episode, including the journal editor's attempts to justify their sloppy reviewing, which just appeared online in the National Center for Science Education's magazine, NCSE Reports. I also blogged about this when it happened, one year ago, as did PZ Myers (Pharyngula), Attila Csordas, and Lars Juhl Jensen. The article appears as "retracted" on the journal website, with the explanation that the retraction was due to plagiarism (most of the article was blatantly plagiarized), but no comment at all about the Creationism claims.

Ironically, this article - although retracted! - was the #2 most-accessed article for the journal for the entire year of 2008, according to the journal's website. I guess people were interested in seeing what all the fuss was about.

The Creationist claim and the plagiarism were discovered by bloggers and blog readers, and sent to the journal. The journal's chief editor was initially very concerned, but he quickly became defensive, and never made a public statement on the Creationist claims, instead defending the review process and the anonymous reviewers.

Luckily we stopped them this time. But it's a cautionary tale for those of us who regularly review papers in the scientific literature.