Content of review 1, reviewed on June 01, 2021

Thank you for your interesting paper and your efforts to add anew piece in diagnosing and detecting high risk patients for cancer breast. However authors need to consider the following:

Comments on abstract, title, references: Thank you for your interesting paper with a clear and concise aim. However, the authors need to consider the following; 1-The title is needed to include names of the specific gene in which the new SNPs were identified. 2-The background is very defective, and the aim is repeated twice in two different ways. 3-The study results were found to need more clarification in the abstract, no statistical data mentioned the control samples all over the article, and significance measures are not mentioned. 4-The summary of the method used in the study is mentioned in the abstract in a very shortage. 5-The conclusion in the abstract is confused with the limitations of the study. 6-Finally, in the abstract, some little English editing needed to be done, like adding some commas, using correct articles, and unifying the American or British English words as in analyse. 7-The references need to be more recent. There are redundant references for a single paragraph or a single sentence. Multiple references can be replaced by only one, the most recent reference, like references from 1-2, 3-8, and 9-12. However, the references are ordered correctly, and appropriate key studies are included.

Comments on introduction/background The authors need to consider the following regarding the introduction; 1-The multiple references used for single statements can be replaced by more recent systematic reviews like: van den Broek AJ, Schmidt MK, van 't Veer LJ, Tollenaar RAEM, and van Leeuwen FE. Worse Breast Cancer Prognosis of BRCA1/BRCA2 Mutation Carriers: What's the Evidence? A Systematic Review with Meta-Analysis. PLOS ONE, 27 -March 2015.DOI:10.1371/journal.pone.0120189. Baretta Z., Mocellin S., Goldin E., Olopade O.I., and Huo D. Effect of BRCA germline mutations on breast cancer prognosis.A systematic review and meta-analysis. Medicine (Baltimore). 2016 Oct; 95(40): e4975. 2- Regarding the paragraph (Totally converse is the repair system activity by direct lesion reversal, in which there is merely a single-stage process with maintained integrity of the DNA phosphodiester chain and the system of recombination repair (HR).), it is not easily understood and needs more clarification about the HR system as the aim of the study to test the genes of HR-related genes. 3-More details about the BRCA gene and its relation to cancer breast is needed. 4-Explain in you introduction why the current research is important in little more detail. 5-It is needed to state the population involved in the research in the study's aim. The method of answering the research aim is required to be illustrated and the novelty in their study. 6-Finally, some English editing is needed to be done in the introduction, like adding some commas and using correct articles. • ʺMostlyʺ, in the first paragraph, is needed to be replaced by most. • In the statement, ʺ The genes of DNA lesion repair system play the key role in maintaining genome integrity and in controlling the repair of mutation-affected DNA. ʺ, it is needed to replace the key with a key as these factors are not the only factors and remove the second in before controlling. • ʺMalfunction of these genes would result in rapid accumulation of errors within DNA,ʺ, replace the errors within DNA by DNA errors. • ʺThe variability of DNA repair genes may also carry clinical significance when correlated with the risk of development of specific types of cancer,ʺ replace- development of -by developing. • Literature data suggest not suggests. • ʺ….on the attempt to associate ones with clinical manifestation of carcinogenesis.ʺ, replace on the attempt by attempting. • ʺ…which may underline the differences in ones susceptibilityʺ, please write one's with a possessive apostrophe.

The authors need to consider the following regarding the methods section; 1- The selection of the control samples was unclear. Are they other patients but not having cancer breast or completely healthy? I understood from your expression that they are other patients (500 DNA samples collected from unrelated disease-free women selected randomly from the Polish female population of the database of the Biobank Lab, Department of Molecular Biophysics, University of Lodz, served as controls). It is well known that HR-related genes are involved in many disorders, so please clarify this point. 2- Please add the catalogue numbers of the used kits in the study to be easier for other researchers for duplication studies> 3- Why purity and quality of extracted DNA not checked? 4- You did not duplicate some samples in your tests to ensure that they give the same results every time, decreasing the reliability of the results. ents on methodology

Comments on data and results

The authors need to consider the following regarding the results section; 1- No demographic data about the controls were demonstrated. 2- Some abbreviations in the tables are not mentioned below the table. 3- P-value, which is less than 0.05, and a confidence interval that does not include the null value (which can vary) were not demonstrated. 5- Defective results presentations either in tables or figures: Regarding tables: Further tables are needed for data analysis like linkage disequilibrium and haplotyping between the studied SNPs. Tables correlating genotypes with the phenotypes were not presented even as supplementary data. SNPs were not statistically analyzed for their risk factor for breast cancer.

Regarding figures: No figures were demonstrated. Figures here are helpful when trends in the data are more important to communicate than the numerical values themselves. -The resultant figure of sequencing was not presented. -The figure of association analysis was not present. 5- No comments were demonstrated on the statistical tests used in the analysis.

The authors need to consider the following regarding the discussion and conclusion section; 1- Please, make a direct, explicit statement of the results of your study at the beginning of the discussion due to the superficial restatements of data. 2- Please, reduce the general information in the discussion as it is not an introduction section to avoid two introduction sections. 3- The discussion section lacks interpretation and alternative explanations. So, please add more details about the discovered SNPs, their locations, their impact on the transcription of their genes, and how they can be related to breast cancer. The conclusions of your study did not answer the aims of the study so, please more clarification is required. 4- Please, add separate titles for the conclusion and the limitations of the study. 5- Please, make suitable comparisons to similar studies. 6- Made suggestions for future research.

Source

    © 2021 the Reviewer.

References

    Hanna, R., Dominik, S., Marcin, S., Marta, S., Ewa, K., Anna, S., Marek, Z., Jan, B., Beata, S. 2017. New single nucleotide polymorphisms (SNPs) in homologous recombination repair genes detected by microarray analysis in Polish breast cancer patients. Clinical and Experimental Medicine.