Title: The rs9953490 polymorphism of DAL-1 gene is associated with gastric cancer risk in the
Han population in Northeast China
Version: 1 Date: 09 Apr 2021
Reviewer's report:
The study of Wang H and Jiang Y et al. explores the putative association of six SNPs, falling
within the DAL-1 gene, with gastric cancer risk in the Han population. The work is concise, but
the design of the study is relatively poor and some information is missing.
For instance, it is not clear how the authors selected the target SNPs within the gene of interest.
According to what it’s written, they used just the allele frequency as a criterion, however, I doubt
that just six SNPs have a MAF higher than 5% in Chinese Han. Please, specify the additional
criteria you have used to select the SNPs (missense, protein-truncating variants, UTR and so on).
The main result is quite interesting: in the dominant model, the SNP rs9953490 seems associated
with GC within smokers, pointing toward a scenario where an interaction is working. The fact
that the significance is not maintained after adjustments may also depend on the covariates you
have used: you write that you have adjusted also for smoking status, which, in my opinion, it
does not make sense, since your analysis was restricted to smokers. Then you also used drinking
habits. However, smoking status is often correlated to drinking habits. It is, therefore, possible
that adjusting also for drinking status may abolish the significant signal you have found.
Anyway, a major problem of the work is that you have done a lot of statistical testing without
checking if your significant results resist multiple test correction. Surely, adding this information
to the work will increase the statistical strength of your results.
My last point is the interpretation of the biological mechanism through which the SNP interact
with the N3 status and TNM stage III. You claim that its location within a regulatory region may
decrease the expression or affect the promoter methylation status of the gene. However, you can
directly check this information in public databases, such as GTEx. Indeed, you could verify that
the presence of the variant influences the gene expression in different tissues.
Minor points:
- If possible, please specify the meaning of the acronyms the first time you use them.
- I have spotted a few grammar errors and some syntax issues. A careful re-examination of the
text is necessary.
- Line 90: dbSNP is the proper name of the database (not UCSC).
- Line 130: Additional file 1 seems to contain allelic counts and not frequencies.
Title: The rs9953490 polymorphism of DAL-1 gene is associated with gastric cancer risk in the
Han population in Northeast China
Version: 1 Date: 09 Apr 2021
Reviewer's report:
The study of Wang H and Jiang Y et al. explores the putative association of six SNPs, falling
within the DAL-1 gene, with gastric cancer risk in the Han population. The work is concise, but
the design of the study is relatively poor and some information is missing.
For instance, it is not clear how the authors selected the target SNPs within the gene of interest.
According to what it’s written, they used just the allele frequency as a criterion, however, I doubt
that just six SNPs have a MAF higher than 5% in Chinese Han. Please, specify the additional
criteria you have used to select the SNPs (missense, protein-truncating variants, UTR and so on).
The main result is quite interesting: in the dominant model, the SNP rs9953490 seems associated
with GC within smokers, pointing toward a scenario where an interaction is working. The fact
that the significance is not maintained after adjustments may also depend on the covariates you
have used: you write that you have adjusted also for smoking status, which, in my opinion, it
does not make sense, since your analysis was restricted to smokers. Then you also used drinking
habits. However, smoking status is often correlated to drinking habits. It is, therefore, possible
that adjusting also for drinking status may abolish the significant signal you have found.
Anyway, a major problem of the work is that you have done a lot of statistical testing without
checking if your significant results resist multiple test correction. Surely, adding this information
to the work will increase the statistical strength of your results.
My last point is the interpretation of the biological mechanism through which the SNP interact
with the N3 status and TNM stage III. You claim that its location within a regulatory region may
decrease the expression or affect the promoter methylation status of the gene. However, you can
directly check this information in public databases, such as GTEx. Indeed, you could verify that
the presence of the variant influences the gene expression in different tissues.
Minor points:
- If possible, please specify the meaning of the acronyms the first time you use them.
- I have spotted a few grammar errors and some syntax issues. A careful re-examination of the
text is necessary.
- Line 90: dbSNP is the proper name of the database (not UCSC).
- Line 130: Additional file 1 seems to contain allelic counts and not frequencies.
Please review this paper.
user
Title: The rs9953490 polymorphism of DAL-1 gene is associated with gastric cancer risk in the
Han population in Northeast China
Version: 1 Date: 09 Apr 2021
Reviewer's report:
The study of Wang H and Jiang Y et al. explores the putative association of six SNPs, falling
within the DAL-1 gene, with gastric cancer risk in the Han population. The work is concise, but
the design of the study is relatively poor and some information is missing.
For instance, it is not clear how the authors selected the target SNPs within the gene of interest.
According to what it’s written, they used just the allele frequency as a criterion, however, I doubt
that just six SNPs have a MAF higher than 5% in Chinese Han. Please, specify the additional
criteria you have used to select the SNPs (missense, protein-truncating variants, UTR and so on).
The main result is quite interesting: in the dominant model, the SNP rs9953490 seems associated
with GC within smokers, pointing toward a scenario where an interaction is working. The fact
that the significance is not maintained after adjustments may also depend on the covariates you
have used: you write that you have adjusted also for smoking status, which, in my opinion, it
does not make sense, since your analysis was restricted to smokers. Then you also used drinking
habits. However, smoking status is often correlated to drinking habits. It is, therefore, possible
that adjusting also for drinking status may abolish the significant signal you have found.
Anyway, a major problem of the work is that you have done a lot of statistical testing without
checking if your significant results resist multiple test correction. Surely, adding this information
to the work will increase the statistical strength of your results.
My last point is the interpretation of the biological mechanism through which the SNP interact
with the N3 status and TNM stage III. You claim that its location within a regulatory region may
decrease the expression or affect the promoter methylation status of the gene. However, you can
directly check this information in public databases, such as GTEx. Indeed, you could verify that
the presence of the variant influences the gene expression in different tissues.
Minor points:
- If possible, please specify the meaning of the acronyms the first time you use them.
- I have spotted a few grammar errors and some syntax issues. A careful re-examination of the
text is necessary.
- Line 90: dbSNP is the proper name of the database (not UCSC).
- Line 130: Additional file 1 seems to contain allelic counts and not frequencies.
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