Review for 10.1186/s12876-014-0203-0 (2014)

Reviewer's report
Title:Differences in the genetic alterations between Vietnamese and Japanese
colorectal cancers
Version:3Date:25 August 2014
Reviewer: Barbara Pardini
Reviewer's report:
Second revision of the manuscript by Miwata et al (MS: 1208173965133018).
The work of Miwata and coauthors has not been improved as requested from
both the Reviewers.
In particular, the following points have still not been covered:
1) Both Reviewers were pointing out the reduced dimension of the population
under study. We understand that it may not be possible to enlarge the sample
group, but Reviewer 1 was suggesting to report some data from the literature (if
any). Authors did not even consider this suggestion and they just reply in the
same way to both Reviewers. In addition, the fact that they found significant
differences it is not a sufficient reason for not enlarging the group of study. As it
is the 2 groups are not comparable.
2) Both Reviewers recommended a rephrasing and rewriting of the Discussion
and a clarification of the aim of the study in the Discussion. Authors did not touch
anything in the Discussion: they just moved the last paragraph (a well know
classification of colorectal cancer pathways) into the Introduction. Adding a
sentence “A more detailed view is needed, of course” is not a sufficient revision.
Moreover, the paragraph added in the Introduction did not help in clarifying the
aim of the study: it is not clear yet the reason of the choice of the specific
biomarkers selected
3) Reviewer 1 was pointing out that the study analyzed somatic mutations and
was asking not to use “genetic pathways” since it was not correct. Authors
changed “genetic pathways” with “genetic alterations” which is misleading as the
previous term..
4) Both Reviewers criticized Figures as they were of really poor quality. The
justification given by authors was: “Figures B and C are images of microsatellite
assay. The assay shows ladder-like or smear-like band shadows. Therefore, the
bands seem to be unclear, but not unclear.” What do these sentences mean?
5) Reviewer 2 asked for being more clear in the Abstract on the number of
subjects analyzed. The suggestion has not been taken into consideration.
6) Reviewer 2 asked for a revision of the language by a native speaker. It is
obvious that this has not been done since the reply to Reviewers is full of
mistakes (for instance “we have fully understanding”) and all over the manuscript
there are no changes of the previous errors found..
7) Reviewer 2 was pointing out the presence of a bias in the period of sampling
of the 2 groups. The reply by authors considered only environmental exposure
and cultural habits. The main problem from the epidemiological point of view in
the comparison of small sampling of 12-years or of 2-years consist in differences
in the diagnosis (in 12 years colorectal cancer prevention has improved lot), in
the time distribution of samples recruitment (especially for 12 years long
sampling, you can have 70% of samples collected in the first 5 years with
methodologies that could be really different after additional 7 years especially in
a developed country like Japan..). At least Authors should have considered and
discussed this point among the limitations of the study..
8) From the epidemiological point of view colorectal cancer patients aged 50
years old are not considered early onset patients.. Again, Authors confused the
terms. Early onset cancer samples are a group of patients having ALL an early
age of onset. It is not a question of mean age. The two study group included in
the study spanned a range of age comparable but it is the internal distribution of
the age of cases that was different (you can see from the different mean). This
difference would have been probably even more notable if Authors have shown
median age.