Reviewer's report 
 Delayed diagnosis of coeliac disease increases cancer risk Title: 
 1  4 October 2006 Version: Date: 
 Timothy Richard Card Reviewer: 
Reviewer's report: 
General 
This is a further paper looking at the association between malignancy and coeliac disease. It is somewhat 
different to many others in that it examines malignancy diagnosed before or simultaneous with the diagnosis 
of Coeliac disease. Though this confers some novelty it also unfortunately ensures that the study cannot be 
easily interpretted as there is a great risk of bias in the ascertainment of the diagnosis of coeliac disease. It 
is of course to avoid this problem that it is conventional not only not to study pre-existing diagnoses of 
cancer in such studies, but also to censor those from the early part of follow up. To put it more simply we cannot come to any reasonable conclusion about whether this paper shows that people with cancer see doctors more and therefore more commonly have their coeliac disease detected, or people with coeliac 
disease get more cancer. This problem I believe since it results from the fundamental design of the study 
cannot be overcome by revision of the paper, and the authors have neither addressed it in their discussion nor suggested any clear benefit of their study design which could render it valid. The best explanation I can see for the study design used is that the authors wish to look at the effect of more prolonged gluten 
containing diet, and hence have used age at diagnosis as a proxy for duration of coeliac disease not treated 
by diet. I note with interest that they feel that the greater age of those with cancer is evidence that prolonged 
gluten exposure is carcinogenic. Unfortunately I feel one could contend with at least equal validity that the 
results found in this respect reflect only the well known fact that malignancy is in general more common with 
advancing age. I regret therefore that I cannot recommend publication of this paper. 
------------------------------------------------------------------------------- Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Reject because scientifically unsound What next?: 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Reviewer's report 
 Delayed diagnosis of coeliac disease increases cancer risk Title: 
 1  4 October 2006 Version: Date: 
 Timothy Richard Card Reviewer: 
Reviewer's report: 
General 
This is a further paper looking at the association between malignancy and coeliac disease. It is somewhat 
different to many others in that it examines malignancy diagnosed before or simultaneous with the diagnosis 
of Coeliac disease. Though this confers some novelty it also unfortunately ensures that the study cannot be 
easily interpretted as there is a great risk of bias in the ascertainment of the diagnosis of coeliac disease. It 
is of course to avoid this problem that it is conventional not only not to study pre-existing diagnoses of 
cancer in such studies, but also to censor those from the early part of follow up. To put it more simply we cannot come to any reasonable conclusion about whether this paper shows that people with cancer see doctors more and therefore more commonly have their coeliac disease detected, or people with coeliac 
disease get more cancer. This problem I believe since it results from the fundamental design of the study 
cannot be overcome by revision of the paper, and the authors have neither addressed it in their discussion nor suggested any clear benefit of their study design which could render it valid. The best explanation I can see for the study design used is that the authors wish to look at the effect of more prolonged gluten 
containing diet, and hence have used age at diagnosis as a proxy for duration of coeliac disease not treated 
by diet. I note with interest that they feel that the greater age of those with cancer is evidence that prolonged 
gluten exposure is carcinogenic. Unfortunately I feel one could contend with at least equal validity that the 
results found in this respect reflect only the well known fact that malignancy is in general more common with 
advancing age. I regret therefore that I cannot recommend publication of this paper. 
------------------------------------------------------------------------------- Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Reject because scientifically unsound What next?: 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Please review this paper.
user
Reviewer's report 
 Delayed diagnosis of coeliac disease increases cancer risk Title: 
 1  4 October 2006 Version: Date: 
 Timothy Richard Card Reviewer: 
Reviewer's report: 
General 
This is a further paper looking at the association between malignancy and coeliac disease. It is somewhat 
different to many others in that it examines malignancy diagnosed before or simultaneous with the diagnosis 
of Coeliac disease. Though this confers some novelty it also unfortunately ensures that the study cannot be 
easily interpretted as there is a great risk of bias in the ascertainment of the diagnosis of coeliac disease. It 
is of course to avoid this problem that it is conventional not only not to study pre-existing diagnoses of 
cancer in such studies, but also to censor those from the early part of follow up. To put it more simply we cannot come to any reasonable conclusion about whether this paper shows that people with cancer see doctors more and therefore more commonly have their coeliac disease detected, or people with coeliac 
disease get more cancer. This problem I believe since it results from the fundamental design of the study 
cannot be overcome by revision of the paper, and the authors have neither addressed it in their discussion nor suggested any clear benefit of their study design which could render it valid. The best explanation I can see for the study design used is that the authors wish to look at the effect of more prolonged gluten 
containing diet, and hence have used age at diagnosis as a proxy for duration of coeliac disease not treated 
by diet. I note with interest that they feel that the greater age of those with cancer is evidence that prolonged 
gluten exposure is carcinogenic. Unfortunately I feel one could contend with at least equal validity that the 
results found in this respect reflect only the well known fact that malignancy is in general more common with 
advancing age. I regret therefore that I cannot recommend publication of this paper. 
------------------------------------------------------------------------------- Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
 Reject because scientifically unsound What next?: 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
assistant