Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:4 October 2011
Reviewer: Richard Ferrero
Reviewer's report:
General comments:
Watada and colleagues have investigated correlations between novel candidate
virulence genes with cagA, a marker of more virulent Helicobacter pylori strains,
and the association of these novel genes with clinical outcomes in Columbian
and Japanese populations. From previous microarray studies, the authors
identified nine genes as being significantly correlated with the presence of cagA;
they selected four of these for examination in 177 Colombian and 169 Japanese
H. pylori strains. The key finding of the work was the identification of two genes
(jhp0045 and jhp0046) as markers for gastric cancer in cagA-positive cases in
Colombia, but not for cases of gastric cancer in Japan. Although this is a
relatively modest observation it does illustrate the limitations of using
cagA-positivity alone as a predictor for more severe forms of H. pylori-associated
disease. Furthermore, the work identifies additional bacterial factors that may be
important as promoters of gastric carcinogenesis and also demonstrates how the
etiology of this disease may vary between different human populations. The
authors need to address the specific comments below.
Major compulsory revisions:
None
Minor essential revisions:
1) (Throughout) The manuscript needs to be edited by a native English speaker.
2) (pg 8) The authors should give as much information as possible on the
different genes/ORFs i.e. Are these conserved hypothetical genes? In which of
the sequenced H. pylori genomes are these genes found? The authors also need
to address why they investigated two of the ORFs (jhp0967 and jhp0951), which
are associated with duodenal ulcer (DU) disease, when it is commonly accepted
that DU and gastric cancer are mutually exclusive diseases.
3) (pg 23) From “eye balling” of the numbers, it seems surprising that there is a
significant association between the carriage of jhp0045 and jhp0046 in H. pylori
strains and gastric cancer development (32.6% and 37%, respectively) when
compared with gastritis (11.4% and 18.2%, respectively), yet there is no
association with duodenal ulcer disease (28.6% and 28.6%, respectively).
Discretionary revisions:
4) (pg 20) What are PZ1 and PZ2?
5) (Tables 3 and 4) For consistency, the data in the two tables should be
presented in the same order. i. e. Japanese strains then those from Columbia.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
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.
Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:4 October 2011
Reviewer: Richard Ferrero
Reviewer's report:
General comments:
Watada and colleagues have investigated correlations between novel candidate
virulence genes with cagA, a marker of more virulent Helicobacter pylori strains,
and the association of these novel genes with clinical outcomes in Columbian
and Japanese populations. From previous microarray studies, the authors
identified nine genes as being significantly correlated with the presence of cagA;
they selected four of these for examination in 177 Colombian and 169 Japanese
H. pylori strains. The key finding of the work was the identification of two genes
(jhp0045 and jhp0046) as markers for gastric cancer in cagA-positive cases in
Colombia, but not for cases of gastric cancer in Japan. Although this is a
relatively modest observation it does illustrate the limitations of using
cagA-positivity alone as a predictor for more severe forms of H. pylori-associated
disease. Furthermore, the work identifies additional bacterial factors that may be
important as promoters of gastric carcinogenesis and also demonstrates how the
etiology of this disease may vary between different human populations. The
authors need to address the specific comments below.
Major compulsory revisions:
None
Minor essential revisions:
1) (Throughout) The manuscript needs to be edited by a native English speaker.
2) (pg 8) The authors should give as much information as possible on the
different genes/ORFs i.e. Are these conserved hypothetical genes? In which of
the sequenced H. pylori genomes are these genes found? The authors also need
to address why they investigated two of the ORFs (jhp0967 and jhp0951), which
are associated with duodenal ulcer (DU) disease, when it is commonly accepted
that DU and gastric cancer are mutually exclusive diseases.
3) (pg 23) From “eye balling” of the numbers, it seems surprising that there is a
significant association between the carriage of jhp0045 and jhp0046 in H. pylori
strains and gastric cancer development (32.6% and 37%, respectively) when
compared with gastritis (11.4% and 18.2%, respectively), yet there is no
association with duodenal ulcer disease (28.6% and 28.6%, respectively).
Discretionary revisions:
4) (pg 20) What are PZ1 and PZ2?
5) (Tables 3 and 4) For consistency, the data in the two tables should be
presented in the same order. i. e. Japanese strains then those from Columbia.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
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.
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:4 October 2011
Reviewer: Richard Ferrero
Reviewer's report:
General comments:
Watada and colleagues have investigated correlations between novel candidate
virulence genes with cagA, a marker of more virulent Helicobacter pylori strains,
and the association of these novel genes with clinical outcomes in Columbian
and Japanese populations. From previous microarray studies, the authors
identified nine genes as being significantly correlated with the presence of cagA;
they selected four of these for examination in 177 Colombian and 169 Japanese
H. pylori strains. The key finding of the work was the identification of two genes
(jhp0045 and jhp0046) as markers for gastric cancer in cagA-positive cases in
Colombia, but not for cases of gastric cancer in Japan. Although this is a
relatively modest observation it does illustrate the limitations of using
cagA-positivity alone as a predictor for more severe forms of H. pylori-associated
disease. Furthermore, the work identifies additional bacterial factors that may be
important as promoters of gastric carcinogenesis and also demonstrates how the
etiology of this disease may vary between different human populations. The
authors need to address the specific comments below.
Major compulsory revisions:
None
Minor essential revisions:
1) (Throughout) The manuscript needs to be edited by a native English speaker.
2) (pg 8) The authors should give as much information as possible on the
different genes/ORFs i.e. Are these conserved hypothetical genes? In which of
the sequenced H. pylori genomes are these genes found? The authors also need
to address why they investigated two of the ORFs (jhp0967 and jhp0951), which
are associated with duodenal ulcer (DU) disease, when it is commonly accepted
that DU and gastric cancer are mutually exclusive diseases.
3) (pg 23) From “eye balling” of the numbers, it seems surprising that there is a
significant association between the carriage of jhp0045 and jhp0046 in H. pylori
strains and gastric cancer development (32.6% and 37%, respectively) when
compared with gastritis (11.4% and 18.2%, respectively), yet there is no
association with duodenal ulcer disease (28.6% and 28.6%, respectively).
Discretionary revisions:
4) (pg 20) What are PZ1 and PZ2?
5) (Tables 3 and 4) For consistency, the data in the two tables should be
presented in the same order. i. e. Japanese strains then those from Columbia.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
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.
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