Single-Nucleotide Polymorphisms in Capecitabine Bioactivation Genes and Their Contribution to Breast Cancer Therapy

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Editorial Board and Authors:

 Thank you for inviting me to review the manuscript entitled "Single Nucleotide Polymorphisms in Capecitabine Bioactivation Genes and Their Contribution to Breast Cancer Therapy Effectiveness". This study focuses on evaluating the effect of single-nucleotide polymorphisms (SNPs) in genes involved in the bioactivation of capecitabine on progression-free survival (PFS) in patients with breast cancer (BC) , with a view to identifying potential biomarkers for predicting the efficacy of capecitabine. The paper's topic selection is appropriate, the overall research design is sound, and the conclusions are consistent with the data. In summary, this represents a valuable contribution. However, certain aspects still require revision and refinement. Specific suggestions for modification are as follows:

1. The abstract is well-structured and includes a summary of the background, methods, key results and conclusions presented in the manuscript. Please note, however, that statistical symbols such as p-values should generally be presented in italics when they appear in both the abstract and the main text.
2. When an abbreviation appears for the first time in the abstract or main text, both the full term and the abbreviation should be provided. Thereafter, the abbreviation may be used in the abstract and main text. Please correct instances in the introduction where certain terms are repeatedly given in both their full form and abbreviated form, such as single-nucleotide polymorphisms (SNPs).
3. SNPs mentioned in the article, such as rs71647871and rs602950, should generally be written in italics.
4. The Methods section of the manuscript states that the dosage range for capecitabine was 1,500 to 4,300 mg per day. Were there any patients whose dose was reduced during the treatment cycle due to toxicity? We recommend providing further details regarding the treatment, as this is a key confounding factor affecting efficacy.
5. In the Results section, the 95% confidence interval for CES1 rs71647871is 1.24 - 122.52, with an upper limit of 122.52. It is recommended that a brief statistical explanation be provided, and that the limitations section note that this finding could be further validated in a larger cohort study.
6. The discussion section references the findings of Liu et al. and Martin et al., which indicate that the CDA rs602950-C allele is associated with shorter PFS, however, the present study found that the TT genotype is associated with shorter PFS. It is recommended that one or two additional references regarding inconsistent directional effects of CDA SNPs across different cancer types or ethnic groups be included in the introduction to emphasise the necessity of this study. The authors consider that the differences in the results may stem from variations in the treatment regimens employed and the patients’ ethnic backgrounds, but this is not discussed in depth. As CDA rs602950is located in the promoter region, its impact on transcriptional activity may vary depending on factors such as the microenvironment; it is recommended that this aspect be further discussed and supported by additional references.

 

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Fernández et al., evaluated the effect of SNPs in genes involved in the bio-activation of capecitabine on progression-free survival (PFS) in patients with BC. Findings of the study suggested that CES1 rs71647871 and CDA rs602950 may serve as predictive biomarkers of capecitabine effectiveness in patients with BC.

Overall, it is a significant study that may be helpful for the researchers and clinicians working on cancer therapeutics.

There are some suggestions, which may be incorporated

Title: word effectiveness may be removed

Abstract: A sentence with future direction/work may be added at the end of the conclusion

Introduction: Well written, describing the research problem effectively

Methods: In study population, a subheading as dosage/on going treatment may be a good addition

P values may be added into the tables e.g. table 2

If possible, figures can be improved

Discussion may be expanded with some evidence-based findings

Conclusion: it may also be expanded, as it is too short, some limitations, and future directions may be narrated here

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Editorial Board and Authors:

Thank you for inviting me to review the manuscript entitled "Single Nucleotide Polymorphisms in Capecitabine Bioactivation Genes and Their Contribution to Breast Cancer Therapy Effectiveness". This study focuses on evaluating the effect of single-nucleotide polymorphisms (SNPs) in genes involved in the bioactivation of capecitabine on progression-free survival (PFS) in patients with breast cancer (BC) , with a view to identifying potential biomarkers for predicting the efficacy of capecitabine. The paper's topic selection is appropriate, the overall research design is sound, and the conclusions are consistent with the data. In summary, this represents a valuable contribution. However, the methodology requires further revision and refinement. Specific suggestions for revision are as follows:

The methods section of the article mentions that the False Discovery Rate (FDR) method was used for multiple testing correction to control for Type I errors. The results section states that these associations remained significant after FDR corrections. We recommend adding details regarding the sample size calculations and power analysis, and clearly specifying the exact significance thresholds used following correction.

Author Response

Please see the attachment.

Author Response File: Author Response.docx