Review for 10.1186/s12876-015-0336-9 (2015)

Reviewer's report
Title:Polymorphisms of the PRLHR, HSPA12A and Risk of Gastric Cancer,
Colorectal Cancer in the Chinese Han Population
Version:2Date:30 June 2015
Reviewer: Tine Kopp
Reviewer's report:
Reviewer comments to the manuscript entitled: “Polymorphisms of the PRLHR,
HSPA12A and Risk of Gastric Cancer, Colorectal Cancer in the Chinese Han
Population”.
The aim of the study was to examine a possible relation between single
nucleotide polymorphisms (SNP) in seven genes. The study is a case-control
study consisting of 588 gastric cancer cases, 449 colorectal cancer cases and
703 healthy controls from the Han Chinese population. One of the SNPs in
PRLHR is associated with decreased risk of colorectal cancer, and another SNP
in HSPA12A is associated with reduced risk of gastric cancer.
Overall, I would recommend that the authors use a translator in order to improve
the language. There are several misspellings, but also a lot of sentences that are
very difficult to understand due to language problems.
Below are my main concerns:
1. In the introduction, the authors describe that they will investigate
polymorphism in two genes (PRLHR and HSPAI1A), but in the abstract,
genotyping and results, seven genes are mentioned. In the Table 3, seven SNPs
are shown, but only five genes are listed. You should clarify this issue – how
many genes are you investigating and how many SNPs in each gene? This is
NOT clear.
2. The authors need to describe why the use the two/five/seven genes and their
relation to gastric and colorectal cancer; and also, why and how did they select
the seven SNPs. Are the SNPs functional or not? In the introduction, GWAS are
mentioned in relation to PRLHR and HSPAI1A and digestive cancer, but there
are no references. The authors should shortly describe all available studies on
the genes, SNPs and their relation to gastric and colorectal cancer.
3. All gene names should be written in italic typing whereas proteins should not.
It is difficult to know when the authors are describing the gene or the protein.
4. In the method section, under study population, a detailed description of the
study population should be given including further details about inclusion and
exclusion criteria. Alternatively, the authors could use a reference if the study
population has been described in details elsewhere. The authors also describe
some environmental factors and their importance, but they do not use them.
Since both types of cancer are known to be associated with several dietary
factors including alcohol, red meat and fibre intake, these could be potential
confounders and should be corrected for.
5. With regard to statistical analyses, six models have been used for every SNP
resulting in 42 tests. Since there are no a priori hypotheses with regard to the
genes used and their relation to cancer, Bonferroni correction should be used.
Bonferroni correction of the 42 test would result in a significance level of the
p-value of less the 0.001, and hence, none of the results are significant. I do not
think that the study is too small for main effects, but the authors should do a
power analysis to calculate how big an effect they should be able to detect.
Moreover, I don’t think it is necessary to do so many tests on each SNP. The
appropriate way would be to first analyse the OR of each genotype and then
decide what its function is. Is it dominant, recessive etc. and then you should do
the most suitable test. That is, only one test per SNP, alternatively two if it is not
clear how the SNP function.
In conclusion, there is a lot of work to be done before it should be considered for
publication. Overall, my comments are in the category: “Major Compulsory
Revisions”.
Yours sincerely,
Tine Iskov Kopp, M.Sc., Ph.d.
Research Centre for Prevention and Health
Glostrup University Hospital
Denmark
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, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests