August 20, 2019

expert reaction to study looking at antibiotic use and bowel cancer risk

Research, published in Gut, reports that antibiotic use is linked to higher bowel cancer risk, and lower risk of rectal cancer.

Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:

“This is a careful and well-conducted study in my view.  It has advanced what is known about possible associations between antibiotic use and bowel cancer in potentially important ways.  But it hasn’t given me, personally, any strong concerns about my own past use of antibiotics and my risk of bowel cancer.

“The study has many strengths, and in particular it used a large UK database that’s generally considered to be representative of the UK population.  It is an observational study, and like all such studies it can’t establish what causes what beyond reasonable doubt.  The problem is that people who have taken oral antibiotics will differ from people who haven’t taken them in several ways, and it remains possible that one of these other differences might be the explanation for any differences in cancer rates, and not the actual effect of the antibiotics at all.  But the researchers adjusted their statistical results quite extensively to allow for some of these other differences.  Such adjustments can never be perfect, and adjustments can’t be made for factors on which the researchers have no data.  The researchers acknowledge that this could matter – for instance they point out that they had no data on what the participants ate, their physical activity, or their family history.  All these things are known to relate to bowel cancer risk, and if for some reason they happened to be different in people who had and hadn’t used antibiotics, that could interfere with the estimates of the effects of antibiotics on risk.

“That said, this study does at least provide evidence of associations between antibiotic use and bowel cancer that can and should be followed up in future research.  And the picture appears to be pretty complicated.  The risks depend on which part of the bowel might be affected, on the type of antibiotic, on how long ago the antibiotics were taken, and on how many days antibiotics were taken for.  It’s important to note that taking antibiotics, or some types of antibiotic at least, is associated with a reduced risk of cancer in some parts of the bowel (the rectum) as well as increased risk in others.  And, because of the way the study was designed, it could not investigate whether the way risks changed with different amounts of antibiotic use were the same at different ages.

“One important point, though, is that most of the associations between antibiotic use and bowel cancer rates were not particularly strong.  In most cases, antibiotic use of various kinds didn’t change the risk of various cancers (measured in odds) up or down by more than about 15% in relative terms, in either direction.  Out of every 100 men in the UK, about 7 will be diagnosed with bowel cancer at some time in their life, and the corresponding figure for women is about 6 in every 100.  A relative 15% increase in the chance (odds) of bowel cancer, if it applied to everyone, would mean there would be about one extra case in every 100 men, and also about one extra case in every 100 women.  Not a vast increase.  And a relative decrease of 15% would mean about one fewer case in every 100 men and also in every 100 women.  In fact, because we can’t be sure that antibiotics are the cause of any increased or decreased risk, and because the patterns of risk found in this study depend in a complicated way on so many things, the actual changes in bowel cancer rates if antibiotic prescribing changed a lot would be considerably less than one case per 100 in either direction.

“Overall antibiotic use is worth researching more in relation to bowel cancer risk, and there are important reasons not connected to bowel cancer (to avoid increasing antibiotic resistance in bacteria) for reducing antibiotic use where possible.  But for me at least, the associations observed in this new research are not strong enough to give any major cause for concern on bowel cancer depending on what antibiotics someone might or might not have taken in their lives.”

Dr Ian Johnson, Nutrition researcher and Emeritus Fellow, Quadram Institute Bioscience, said:

“This is a very interesting study but the findings are rather complex.  The increased risk of colon cancer in people receiving the highest exposure to some types of antibiotics was apparently about fifteen percent, comparable in magnitude to the risk associated with, for example, regular consumption of processed meat.  However, for some classes of antibiotic, the increased risk for cancer of the colon seems to be partially offset by a reduced risk of rectal cancer.

“In any case, the public should not be too concerned because, for individuals, the changes in absolute risk are relatively low.

“This was an observational study, with no proven mechanism, but the authors speculate that exposure to antibiotics influences carcinogenesis in the large intestine by modifying the composition of the resident microbiome along the length of the organ.  This is a plausible hypothesis but such effects are poorly understood, and they will now need to be explored in detail.  In the mean time these results do add to the accumulating evidence that exposure to antibiotics may disrupt the natural bacterial populations of the human body in ways that are not necessarily without adverse consequences.”

‘Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study’ by Jiajia Zhang et al. was published in Gut at 23:30 UK time on Tuesday 20 August 2019. 

DOI: 10.1136/gutjnl-2019-318593

Declared interests

Prof Kevin McConway: “Prof McConway is a member of the SMC Advisory Committee, but his quote above is in his capacity as a professional statistician.”

Dr Ian Johnson: “No interests to declare.”