Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 1Date:21 September 2010
Reviewer: Karsten Schulmann
Reviewer's report:
The manuscript entitled „The MLH1 2101C>A (Q701K) variation is related to risk
of gastric cancer in Chinese males“ by Zhi et al. Reports on data of MLH1
germline mutations in unselected 236 gastric cancer patients from two institutions
in China and 240 matched controls.
They found six MLH1 sequence variants among 236 cases. No mutation was an
obvious pathogenic germline mutation (frameshift, nonsense, splice site
mutation, exon deletion). Five sequence variants were not associated with an
increased (or decreased) gastric cancer risk compared to controls.
The 2101C>A mutation was not associated with an increased gastric cancer risk
overall; however in the subgroup of males they identified an increased gastric
cancer risk (OR 8.42 (95% CI 1.04-68.06) with a moderate significance level of
p= 0.041. This correlation was not observed in females. In addition, they reported
a correlation with younger age; however this finding was not significant.
The 2101C>A mutation was scored as tolerant using SIFT score which supports
not an altered protein function.
Major points:
The section regarding the exon splicing of the 2101C>A mutation within the
results is not understandable since the results and terms were not introduced in
the method section. As far as the reviewer was able to conclude findings suggest
an influence on the splicing effect of exon 18.
The study design is adequate. However the conclusion must be drawn very
carefully. The findings regarding 2101C>A should be replicated in an
independent set of gastric cancer samples (perhaps exclusively males). In
addition impaired splicing should be investigated analyzing RNA transcripts.
Third, the cancer of the patient should be analyzed for MSI and MMR protein
expression by immunohistochemistry.
Minor points:
The authors state that the polymorphism c. -28 A>G has been so far reported
exclusively in the Chinese population. However, the InSight database has a total
of five entries of this mutation; one was the referenced paper from China;
however there were 4 more non-Asian entries between 2001 and 2008 of this
mutation.
In addition, the manuscript was written by non-native speakers and a revised
manuscript needs significant editing by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 1Date:21 September 2010
Reviewer: Karsten Schulmann
Reviewer's report:
The manuscript entitled „The MLH1 2101C>A (Q701K) variation is related to risk
of gastric cancer in Chinese males“ by Zhi et al. Reports on data of MLH1
germline mutations in unselected 236 gastric cancer patients from two institutions
in China and 240 matched controls.
They found six MLH1 sequence variants among 236 cases. No mutation was an
obvious pathogenic germline mutation (frameshift, nonsense, splice site
mutation, exon deletion). Five sequence variants were not associated with an
increased (or decreased) gastric cancer risk compared to controls.
The 2101C>A mutation was not associated with an increased gastric cancer risk
overall; however in the subgroup of males they identified an increased gastric
cancer risk (OR 8.42 (95% CI 1.04-68.06) with a moderate significance level of
p= 0.041. This correlation was not observed in females. In addition, they reported
a correlation with younger age; however this finding was not significant.
The 2101C>A mutation was scored as tolerant using SIFT score which supports
not an altered protein function.
Major points:
The section regarding the exon splicing of the 2101C>A mutation within the
results is not understandable since the results and terms were not introduced in
the method section. As far as the reviewer was able to conclude findings suggest
an influence on the splicing effect of exon 18.
The study design is adequate. However the conclusion must be drawn very
carefully. The findings regarding 2101C>A should be replicated in an
independent set of gastric cancer samples (perhaps exclusively males). In
addition impaired splicing should be investigated analyzing RNA transcripts.
Third, the cancer of the patient should be analyzed for MSI and MMR protein
expression by immunohistochemistry.
Minor points:
The authors state that the polymorphism c. -28 A>G has been so far reported
exclusively in the Chinese population. However, the InSight database has a total
of five entries of this mutation; one was the referenced paper from China;
however there were 4 more non-Asian entries between 2001 and 2008 of this
mutation.
In addition, the manuscript was written by non-native speakers and a revised
manuscript needs significant editing by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Please review this paper.
user
Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 1Date:21 September 2010
Reviewer: Karsten Schulmann
Reviewer's report:
The manuscript entitled „The MLH1 2101C>A (Q701K) variation is related to risk
of gastric cancer in Chinese males“ by Zhi et al. Reports on data of MLH1
germline mutations in unselected 236 gastric cancer patients from two institutions
in China and 240 matched controls.
They found six MLH1 sequence variants among 236 cases. No mutation was an
obvious pathogenic germline mutation (frameshift, nonsense, splice site
mutation, exon deletion). Five sequence variants were not associated with an
increased (or decreased) gastric cancer risk compared to controls.
The 2101C>A mutation was not associated with an increased gastric cancer risk
overall; however in the subgroup of males they identified an increased gastric
cancer risk (OR 8.42 (95% CI 1.04-68.06) with a moderate significance level of
p= 0.041. This correlation was not observed in females. In addition, they reported
a correlation with younger age; however this finding was not significant.
The 2101C>A mutation was scored as tolerant using SIFT score which supports
not an altered protein function.
Major points:
The section regarding the exon splicing of the 2101C>A mutation within the
results is not understandable since the results and terms were not introduced in
the method section. As far as the reviewer was able to conclude findings suggest
an influence on the splicing effect of exon 18.
The study design is adequate. However the conclusion must be drawn very
carefully. The findings regarding 2101C>A should be replicated in an
independent set of gastric cancer samples (perhaps exclusively males). In
addition impaired splicing should be investigated analyzing RNA transcripts.
Third, the cancer of the patient should be analyzed for MSI and MMR protein
expression by immunohistochemistry.
Minor points:
The authors state that the polymorphism c. -28 A>G has been so far reported
exclusively in the Chinese population. However, the InSight database has a total
of five entries of this mutation; one was the referenced paper from China;
however there were 4 more non-Asian entries between 2001 and 2008 of this
mutation.
In addition, the manuscript was written by non-native speakers and a revised
manuscript needs significant editing by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
assistant