Reviewer's report
Title:Genetic risk factors for intestinal metaplasia in a high risk
Singapore-Chinese population: a cohort study
Version: 1Date:24 July 2009
Reviewer: charles S rabkin
Reviewer's report:
This manuscript examines the relationship between certain polymorphisms in
candidate genes and intestinal metaplasia in a Singapore-Chinese population.
Significant associations are detected between intestinal metaplasia and the three
polymorphisms examined. The manuscript is well written and commendably
concise. The findings are of interest, but any conclusions should be tempered by
the small sample size.
Major Compulsory Revisions
None.
Discretionary Revisions
1. It is laudable that the authors did a systematic literature review to select the
studied SNPs. Readers would benefit from detailed information provided in a
summary table (maybe as a supplemental material). The additional table would
list the 18 candidate genes/SNPs found to be significantly associated with the
risk of gastric cancer, and the following: study design, sample size, ethnicity of
participants, and risk estimates of the studies should be included, if available.
2. Description of genotyping methods should include quality control procedures
(i.e. genotyping success rate, reproducibility).
3. If data are available, authors should discuss their allele frequencies against
other published data involving Singapore-Chinese populations.
Minor Essential Revisions
1. Given the study design (cross-sectional), the word “risk” should be avoided
and the title of the manuscript modified. Furthermore, information on the study
design of the cohort study from which these subjects were selected should be
provided. Criteria of inclusion, and recruitment time period should be clearly
stated.
2. Additional information on Helicoblot assay must be provided. It is not clear how
the test was interpreted, and what determines a positive status. The lack of this
information prevents this reviewer of fully evaluating the analytic approach of the
study.
3. Results of multivariate analysis (Table 4) suggested that H. pylori status is an
effect modifier of the association between the presence of IM and PTPN11
(GA/AA vs. GG). Please provide evidence of the statistical significance of this
interaction.
4. Authors should mention the guidelines used to classify the gastric lesions.
Please specify if the following classifications were used.
• Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of
gastritis. The updated Sydney System. International Workshop on the
Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996
Oct;20(10):1161-81.
• Rugge M, Correa P, Dixon MF, Hattori T, Leandro G, Lewin K, Riddell RH,
Sipponen P, Watanabe H. Gastric dysplasia: the Padova international
classification. Am J Surg Pathol. 2000 Feb;24(2):167-76.
5. The IM negative group should be fully described in terms of gastric pathology
(i.e. number of subjects with atrophic and non-atrophic gastritis). Were there any
subjects with gastric dysplasia? If so, please indicate how those were handled in
the analysis.
6. Authors should mention genetic models (i.e. dominant, recessive or
codominant) used to guide data analyses.
7. How were “drinker” and “smoker” defined?
8. It is apparent from Table 3 that there were fewer than 374 subjects
successfully genotyped for all the SNPs. Please explain reasons for incomplete
genotyping data.
9. Absolute numbers rather than frequencies are presented in Table 3. Please
alter the title to reflect the results more accurately. Given the uncertainty of the
genetic models, it will be useful to present the three genotypes of each locus. In
addition, rs numbers should be included.
10. Given the large number of SNPs examined, a p-value of <0.05 may be
inappropriate. Authors should discuss the problem of using multiple comparisons.
11. Reference #3 is incomplete.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
Reviewed with Dr. M. Constanza Camargo.
We declare that we have no competing interests.
Reviewer's report
Title:Genetic risk factors for intestinal metaplasia in a high risk
Singapore-Chinese population: a cohort study
Version: 1Date:24 July 2009
Reviewer: charles S rabkin
Reviewer's report:
This manuscript examines the relationship between certain polymorphisms in
candidate genes and intestinal metaplasia in a Singapore-Chinese population.
Significant associations are detected between intestinal metaplasia and the three
polymorphisms examined. The manuscript is well written and commendably
concise. The findings are of interest, but any conclusions should be tempered by
the small sample size.
Major Compulsory Revisions
None.
Discretionary Revisions
1. It is laudable that the authors did a systematic literature review to select the
studied SNPs. Readers would benefit from detailed information provided in a
summary table (maybe as a supplemental material). The additional table would
list the 18 candidate genes/SNPs found to be significantly associated with the
risk of gastric cancer, and the following: study design, sample size, ethnicity of
participants, and risk estimates of the studies should be included, if available.
2. Description of genotyping methods should include quality control procedures
(i.e. genotyping success rate, reproducibility).
3. If data are available, authors should discuss their allele frequencies against
other published data involving Singapore-Chinese populations.
Minor Essential Revisions
1. Given the study design (cross-sectional), the word “risk” should be avoided
and the title of the manuscript modified. Furthermore, information on the study
design of the cohort study from which these subjects were selected should be
provided. Criteria of inclusion, and recruitment time period should be clearly
stated.
2. Additional information on Helicoblot assay must be provided. It is not clear how
the test was interpreted, and what determines a positive status. The lack of this
information prevents this reviewer of fully evaluating the analytic approach of the
study.
3. Results of multivariate analysis (Table 4) suggested that H. pylori status is an
effect modifier of the association between the presence of IM and PTPN11
(GA/AA vs. GG). Please provide evidence of the statistical significance of this
interaction.
4. Authors should mention the guidelines used to classify the gastric lesions.
Please specify if the following classifications were used.
• Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of
gastritis. The updated Sydney System. International Workshop on the
Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996
Oct;20(10):1161-81.
• Rugge M, Correa P, Dixon MF, Hattori T, Leandro G, Lewin K, Riddell RH,
Sipponen P, Watanabe H. Gastric dysplasia: the Padova international
classification. Am J Surg Pathol. 2000 Feb;24(2):167-76.
5. The IM negative group should be fully described in terms of gastric pathology
(i.e. number of subjects with atrophic and non-atrophic gastritis). Were there any
subjects with gastric dysplasia? If so, please indicate how those were handled in
the analysis.
6. Authors should mention genetic models (i.e. dominant, recessive or
codominant) used to guide data analyses.
7. How were “drinker” and “smoker” defined?
8. It is apparent from Table 3 that there were fewer than 374 subjects
successfully genotyped for all the SNPs. Please explain reasons for incomplete
genotyping data.
9. Absolute numbers rather than frequencies are presented in Table 3. Please
alter the title to reflect the results more accurately. Given the uncertainty of the
genetic models, it will be useful to present the three genotypes of each locus. In
addition, rs numbers should be included.
10. Given the large number of SNPs examined, a p-value of <0.05 may be
inappropriate. Authors should discuss the problem of using multiple comparisons.
11. Reference #3 is incomplete.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
Reviewed with Dr. M. Constanza Camargo.
We declare that we have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Genetic risk factors for intestinal metaplasia in a high risk
Singapore-Chinese population: a cohort study
Version: 1Date:24 July 2009
Reviewer: charles S rabkin
Reviewer's report:
This manuscript examines the relationship between certain polymorphisms in
candidate genes and intestinal metaplasia in a Singapore-Chinese population.
Significant associations are detected between intestinal metaplasia and the three
polymorphisms examined. The manuscript is well written and commendably
concise. The findings are of interest, but any conclusions should be tempered by
the small sample size.
Major Compulsory Revisions
None.
Discretionary Revisions
1. It is laudable that the authors did a systematic literature review to select the
studied SNPs. Readers would benefit from detailed information provided in a
summary table (maybe as a supplemental material). The additional table would
list the 18 candidate genes/SNPs found to be significantly associated with the
risk of gastric cancer, and the following: study design, sample size, ethnicity of
participants, and risk estimates of the studies should be included, if available.
2. Description of genotyping methods should include quality control procedures
(i.e. genotyping success rate, reproducibility).
3. If data are available, authors should discuss their allele frequencies against
other published data involving Singapore-Chinese populations.
Minor Essential Revisions
1. Given the study design (cross-sectional), the word “risk” should be avoided
and the title of the manuscript modified. Furthermore, information on the study
design of the cohort study from which these subjects were selected should be
provided. Criteria of inclusion, and recruitment time period should be clearly
stated.
2. Additional information on Helicoblot assay must be provided. It is not clear how
the test was interpreted, and what determines a positive status. The lack of this
information prevents this reviewer of fully evaluating the analytic approach of the
study.
3. Results of multivariate analysis (Table 4) suggested that H. pylori status is an
effect modifier of the association between the presence of IM and PTPN11
(GA/AA vs. GG). Please provide evidence of the statistical significance of this
interaction.
4. Authors should mention the guidelines used to classify the gastric lesions.
Please specify if the following classifications were used.
• Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of
gastritis. The updated Sydney System. International Workshop on the
Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996
Oct;20(10):1161-81.
• Rugge M, Correa P, Dixon MF, Hattori T, Leandro G, Lewin K, Riddell RH,
Sipponen P, Watanabe H. Gastric dysplasia: the Padova international
classification. Am J Surg Pathol. 2000 Feb;24(2):167-76.
5. The IM negative group should be fully described in terms of gastric pathology
(i.e. number of subjects with atrophic and non-atrophic gastritis). Were there any
subjects with gastric dysplasia? If so, please indicate how those were handled in
the analysis.
6. Authors should mention genetic models (i.e. dominant, recessive or
codominant) used to guide data analyses.
7. How were “drinker” and “smoker” defined?
8. It is apparent from Table 3 that there were fewer than 374 subjects
successfully genotyped for all the SNPs. Please explain reasons for incomplete
genotyping data.
9. Absolute numbers rather than frequencies are presented in Table 3. Please
alter the title to reflect the results more accurately. Given the uncertainty of the
genetic models, it will be useful to present the three genotypes of each locus. In
addition, rs numbers should be included.
10. Given the large number of SNPs examined, a p-value of <0.05 may be
inappropriate. Authors should discuss the problem of using multiple comparisons.
11. Reference #3 is incomplete.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
Reviewed with Dr. M. Constanza Camargo.
We declare that we have no competing interests.
assistant