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:15 November 2011
Reviewer: Trine Lembrecht Lembrecht Jorgensen
Reviewer's report:
This is a case-control study that compares statin use in patients with colorectal
cancer against a control group. The authors find a strong protective effect of
statins with an 87% reduced occurrence of colorectal cancer in statin users. The
protective effect is found to be stronger with a higher dose and longer use of
statins. The study seems well conducted. It includes 101 cases and 132 controls
who were all attending for a diagnostic colonoscopy, ensuring controls not to
have an undiagnosed cancer. Information has been collected with regard to type,
dose, and duration of statin use, and data on other potentially confounding
factors have been collected as well. These data have been collected through
patient interviews and review of clinical notes and referral letters.
The question of statins’ role in the prevention of colorectal cancer has been
widely discussed and study results have been diverging. However, there has
been a pattern of randomized clinical trials showing no effect, and case-control
studies showing mostly modest if any protective effect. These findings have been
confirmed in a recent (in this work uncited) meta-analysis by Bardou et al (Effect
of statin therapy on colorectal cancer. Gut.2010;59(11):1572-85). Also, Simon et
al. just published (probably after the submission of this manuscript) a very large
cohort study of more than 12,000 statin users enrolled in the Women’s Health
Initiative. This study finds a marginal protective effect only of lovastatin.
My major concern with this manuscript is that I do not think the results reflect the
true size of association. The effect measures are simply too far off what
numerous other studies have found. Whether there has been an error in the
calculations or there is some behavioral difference between cases and controls
not accounted for, I cannot know. Sample size is low, and perhaps this could
explain erroneous findings too.
Major compulsory revisions
Methods: The selection of cases and controls based on a diagnostic colonoscopy
ensures a true control group with no cancer cases. The procedure of interviewing
recruited patients prior to their colonoscopy is a good method of avoiding recall
bias. However, the authors included some cases after their diagnostic
colonoscopy. The authors should let the reader know what proportion of cases
was included after the diagnostic colonoscopy. What was the reason for this
post-diagnosis inclusion of cases? And were they also patients referred for
diagnostic colonoscopy or were they in any way different from the other cases
and controls? Also, the reason for referral might be of importance. The risk of
having colorectal cancer might be smaller in patients with changes in bowel
habits than in patients with blood in their stool.
Results: I do not understand how the overall OR can end up being smaller than
the ORs of duration and dose of statin use and statin type? What is the reference
of the analysis? No use? All other categories than the one analysed? It would not
seem right to compare e.g. a statin use of < 2 years with no use and a use of > 2
years together.
Discussion: The effect measures found in this study differs markedly from what
has been found in other studies. Possible reasons for this large difference should
be discussed. Further, a discussion of possible residual confounding might be
offered.
Minor essential revisions
Results: p.9, l.14 should be: “There was a highly significant inverse….”
Discussion: p.14, l.10: “…comparable to the age-matched population…”
Table 3: From row “Duration” and down: In the “controls” column numbers of
users (%) are reported (eg 14 (20.6)), whereas in the “CRC” column the authors
report number of exposed in that category out of all statin users and then the
proportion (eg 8/20 (40.0)). This should be uniform
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.