Review for 10.1186/1471-230X-12-36 (2012)

Reviewer's report
Title:Statin use is associated with a reduced incidence of colorectal cancer: a
colonoscopy-controlled case-control study
Version: 1Date:22 November 2011
Reviewer: Yana Vinogradova
Reviewer's report:
The article investigates the effect of statins on the incidence of colorectal cancer
and reaches the conclusion that statins reduce risk of the cancer by 87%. This
would be an exceptional finding if it were the effect of statins and not the more
likely effect of inappropriate study design. My main concern is about the selection
of the controls.
From the study, it appears that the controls are more likely to have family history
of CRC and diabetes and therefore have more reasons to be given regular
scans. The proportion of patients with cardiovascular disease is not made clear
but based on the proportion of statin users the rate of coronary artery disease
appears to be much higher than in the general population. A paper by Goodwin
2011 in Arch Int Med shows that patients with multiple conditions experience
more frequent colonoscopy with no clear indications. The group of controls might
have been screened before – and not long before – which could make the risk of
CRC be lower in such a group. A further point is that statin users might receive
consultations from a dietician and so have healthier diet than non-users –
another reason for reduced CRC risk.
A number of questions spring to mind:
•What were the reasons for the patients’ referrals for colonoscopy? Were they
different for cases and controls?
•How many cases had a post-diagnosis interview and how did they differ from
controls and other cases?
•What were the proportions of cases and controls with coronary artery disease as
the main reason for statin therapy?
•How many cases and controls have had previous colonoscopy and how long
ago?
•Were data on diet collected?
•How was statin dosage defined, particularly for patients taking them for more
than 5 years?
Other minor comments:
Abstract.
The selection criteria for groups of cases and controls need to be described –
whether they are from the general population or some other selection process.
It is not clear from the abstract whether cases had colorectal cancer or any other
cancers before the interview.
The conclusion states that statins have a protective effect, but the paper only
shows that there is an association between reported statin use and reduced risk
of cancer.
Introduction.
I have the impression that papers demonstrating a protective role for statins are
over-represented compared to papers showing the opposite effect. A review of
Boudreau 2010 in Expert Opin Drug Safety listed quite a wide range of long-term
studies on CRC and statins and only Poynter’s paper reported a significant effect
of statin use for 5 years or more.
The authors discuss differences in the designs and weaknesses of various
studies, particularly about measuring statin use from prescription, but do not
mention the latest paper by Jacobs in Cancer Research where the data were
also collected by questionnaire and the use of statins was defined as less than 5
years and more than 5 years.
Page 4 paragraph 1. Ref 11 demonstrated no protective effect of statins but is
included in the list of papers suggesting such an effect.
Page 4 paragraph 2. The authors do not mention that the effect of statins varies
for different types of statins.