Reviewer's report
Title:Investigation of innate immunity genes CARD4, CARD8 and CARD15 as
germline susceptibility factors for colorectal cancer
Version: 1Date:19 May 2009
Reviewer: Frank Grünhage
Reviewer's report:
The authors present a negative association study on different CARD SNPs and
colorectal cancer. The study is well done and although the result is negative it
provides important information for the scientific community. The methods are
sophisticated and the power of the study has been formally assessed. Thus I
have only minor comments that should be addressed in the discussion and may
be taken as suggestions for further studies:
1. Genetic sucsceptibility factors for whatever trait tend to lead to presentation of
affected patients at younger age. Thus, it would have been interesting to look at
a subgroup of patients with earlier manifestation of the CRC (e.g. below 50y).
2. The authors noticed that CRC syndromes are rare and a majority of CRC
cases are sporadic. However, there is also a group of patients (appr. 20%),
which is not well defined and who have a personal or family history of CRC that
does not fulfil HNPCC or FAP criteria but is suspicious of an underlying genetic
susceptibility factor. The likelihood to identify such factors in sporadic cases is
low. Hence, it would have been interesting to look at differences in
allele/genotype distribution between phenotypic extremes such as patients with
early CRC or late CRC
3. By including controls who were older than the cases, the authors excluded to
assign patients who might develop CRC in the future. However, this approach
does not exclude controls with undetected colorectal adenoma. Thus the ideal
controls are age matched with no personal or family history of colorectal
adenoma and a normal colonoscopy, so called hyper normal controls.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Investigation of innate immunity genes CARD4, CARD8 and CARD15 as
germline susceptibility factors for colorectal cancer
Version: 1Date:19 May 2009
Reviewer: Frank Grünhage
Reviewer's report:
The authors present a negative association study on different CARD SNPs and
colorectal cancer. The study is well done and although the result is negative it
provides important information for the scientific community. The methods are
sophisticated and the power of the study has been formally assessed. Thus I
have only minor comments that should be addressed in the discussion and may
be taken as suggestions for further studies:
1. Genetic sucsceptibility factors for whatever trait tend to lead to presentation of
affected patients at younger age. Thus, it would have been interesting to look at
a subgroup of patients with earlier manifestation of the CRC (e.g. below 50y).
2. The authors noticed that CRC syndromes are rare and a majority of CRC
cases are sporadic. However, there is also a group of patients (appr. 20%),
which is not well defined and who have a personal or family history of CRC that
does not fulfil HNPCC or FAP criteria but is suspicious of an underlying genetic
susceptibility factor. The likelihood to identify such factors in sporadic cases is
low. Hence, it would have been interesting to look at differences in
allele/genotype distribution between phenotypic extremes such as patients with
early CRC or late CRC
3. By including controls who were older than the cases, the authors excluded to
assign patients who might develop CRC in the future. However, this approach
does not exclude controls with undetected colorectal adenoma. Thus the ideal
controls are age matched with no personal or family history of colorectal
adenoma and a normal colonoscopy, so called hyper normal controls.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Investigation of innate immunity genes CARD4, CARD8 and CARD15 as
germline susceptibility factors for colorectal cancer
Version: 1Date:19 May 2009
Reviewer: Frank Grünhage
Reviewer's report:
The authors present a negative association study on different CARD SNPs and
colorectal cancer. The study is well done and although the result is negative it
provides important information for the scientific community. The methods are
sophisticated and the power of the study has been formally assessed. Thus I
have only minor comments that should be addressed in the discussion and may
be taken as suggestions for further studies:
1. Genetic sucsceptibility factors for whatever trait tend to lead to presentation of
affected patients at younger age. Thus, it would have been interesting to look at
a subgroup of patients with earlier manifestation of the CRC (e.g. below 50y).
2. The authors noticed that CRC syndromes are rare and a majority of CRC
cases are sporadic. However, there is also a group of patients (appr. 20%),
which is not well defined and who have a personal or family history of CRC that
does not fulfil HNPCC or FAP criteria but is suspicious of an underlying genetic
susceptibility factor. The likelihood to identify such factors in sporadic cases is
low. Hence, it would have been interesting to look at differences in
allele/genotype distribution between phenotypic extremes such as patients with
early CRC or late CRC
3. By including controls who were older than the cases, the authors excluded to
assign patients who might develop CRC in the future. However, this approach
does not exclude controls with undetected colorectal adenoma. Thus the ideal
controls are age matched with no personal or family history of colorectal
adenoma and a normal colonoscopy, so called hyper normal controls.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
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