Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:1 September 2011
Reviewer: Alex Boussioutas
Reviewer's report:
This is a correlation study that reports an association between certain H. pylori
genes and Gastric Cancer in a subpopulation of Columbian patients. The authors
selected genes from previous microarray experiments that were correlated with
cagA status and used a subgroup of these genes to assess expression of those
genes in different patient pathologies in Columbian and Japanese cohorts.
I have a number of questions regarding the manuscript.
Major compulsory revisions
1. This addresses virulence factors in the bacteria but the complex interplay
between host and pathogen are not really addressed in this analysis. Were the
populations studied tested for established host polymorphisms that increase the
risk of GC (eg IL-1R)?
2. I have an issue with the methodology used for selection of genes. Microarray
analyses involving correlations require correction for multiple testing. The p
values reported here do not appear to be corrected for multiple testing. This
would reduce some of the significance of the genes reported as correlated to
cagA status. If you perform appropriate multiple testing correction do these
genes still reach significance?
3. I think it is insufficient to perform a multivariate analysis of age and gender for
risk of GC in these populations. There are other risk factors that could be
incorporated that are more relevant for risk of GC (see question 1).
4. It would be relevant to ascertain whether other established H. pylori genetic
markers of risk as mentioned in the manuscript are also relevant to risk in these
cohorts. The results would serve as a positive control if they indeed correlated as
the authors suggest they would.
5. This study seems to investigate presence of genes, however gene expression
would be more relevant. Does the level of expression of the genes being studied
have biologically significant expression differences? There is no data presented
about fold change of gene expression only that there was negative or positive
association with cagA status. Whereas a correlation may be statistically
significant between genes the expression difference may be marginally different
and hence have little biological meaning.
Minor essential revisions
6. There are a number of grammatical errors throughout the manuscript that
would need to be addressed
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
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:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:1 September 2011
Reviewer: Alex Boussioutas
Reviewer's report:
This is a correlation study that reports an association between certain H. pylori
genes and Gastric Cancer in a subpopulation of Columbian patients. The authors
selected genes from previous microarray experiments that were correlated with
cagA status and used a subgroup of these genes to assess expression of those
genes in different patient pathologies in Columbian and Japanese cohorts.
I have a number of questions regarding the manuscript.
Major compulsory revisions
1. This addresses virulence factors in the bacteria but the complex interplay
between host and pathogen are not really addressed in this analysis. Were the
populations studied tested for established host polymorphisms that increase the
risk of GC (eg IL-1R)?
2. I have an issue with the methodology used for selection of genes. Microarray
analyses involving correlations require correction for multiple testing. The p
values reported here do not appear to be corrected for multiple testing. This
would reduce some of the significance of the genes reported as correlated to
cagA status. If you perform appropriate multiple testing correction do these
genes still reach significance?
3. I think it is insufficient to perform a multivariate analysis of age and gender for
risk of GC in these populations. There are other risk factors that could be
incorporated that are more relevant for risk of GC (see question 1).
4. It would be relevant to ascertain whether other established H. pylori genetic
markers of risk as mentioned in the manuscript are also relevant to risk in these
cohorts. The results would serve as a positive control if they indeed correlated as
the authors suggest they would.
5. This study seems to investigate presence of genes, however gene expression
would be more relevant. Does the level of expression of the genes being studied
have biologically significant expression differences? There is no data presented
about fold change of gene expression only that there was negative or positive
association with cagA status. Whereas a correlation may be statistically
significant between genes the expression difference may be marginally different
and hence have little biological meaning.
Minor essential revisions
6. There are a number of grammatical errors throughout the manuscript that
would need to be addressed
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
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:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:1 September 2011
Reviewer: Alex Boussioutas
Reviewer's report:
This is a correlation study that reports an association between certain H. pylori
genes and Gastric Cancer in a subpopulation of Columbian patients. The authors
selected genes from previous microarray experiments that were correlated with
cagA status and used a subgroup of these genes to assess expression of those
genes in different patient pathologies in Columbian and Japanese cohorts.
I have a number of questions regarding the manuscript.
Major compulsory revisions
1. This addresses virulence factors in the bacteria but the complex interplay
between host and pathogen are not really addressed in this analysis. Were the
populations studied tested for established host polymorphisms that increase the
risk of GC (eg IL-1R)?
2. I have an issue with the methodology used for selection of genes. Microarray
analyses involving correlations require correction for multiple testing. The p
values reported here do not appear to be corrected for multiple testing. This
would reduce some of the significance of the genes reported as correlated to
cagA status. If you perform appropriate multiple testing correction do these
genes still reach significance?
3. I think it is insufficient to perform a multivariate analysis of age and gender for
risk of GC in these populations. There are other risk factors that could be
incorporated that are more relevant for risk of GC (see question 1).
4. It would be relevant to ascertain whether other established H. pylori genetic
markers of risk as mentioned in the manuscript are also relevant to risk in these
cohorts. The results would serve as a positive control if they indeed correlated as
the authors suggest they would.
5. This study seems to investigate presence of genes, however gene expression
would be more relevant. Does the level of expression of the genes being studied
have biologically significant expression differences? There is no data presented
about fold change of gene expression only that there was negative or positive
association with cagA status. Whereas a correlation may be statistically
significant between genes the expression difference may be marginally different
and hence have little biological meaning.
Minor essential revisions
6. There are a number of grammatical errors throughout the manuscript that
would need to be addressed
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
assistant