PONE-D-21-14829Association of PROGINS PgR Polymorphism with susceptibility to female reproductive cancer: A meta-analysis based on 30 studiesPLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

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Reviewer #1: This study is a meta-analysis of the association between PgR gene polymorphisms and female reproductive cancer. This is a very interesting study, but I would like to point out the following points.

Major comments

１． Most of the papers that authors adopted for this meta-analysis are on cancers that occur in specific organs (breast, endometrial, and ovarian cancer) and gene polymorphisms in PgR. Does the role of PgR play a similar role in each of these organs? Is it justified to perform a meta-analysis together with female reproductive cancer without considering organ specificity?　 For example, past epidemiological studies have shown that hormone replacement therapy, including progesterone, has different effects on breast and endometrial cancer risks.

２． From the viewpoint of Comment 1, the interpretation of the results of this study, which examined the relationship between female reproductive cancer and gene polymorphisms in PgR, is difficult to interpret and seems to have low clinical significance.　 I think it is more clinically significant to focus on organ-specific meta-analysis and discuss whether there are any differences.

Minor moment

３． Abstract

In the Material and Method section, it is said that the analysis was performed for the race, cancer, and HWE groups, but the in section of Result, the description of the analysis result is only for race.

4. Figure 1

Check if the numbers in the study consort are correct.　 The total number of excluded studies and the number of non-excluded studies do not match.

Reviewer #2: Detailed comments for the author's consideration

Review of the paper by �Chen Zhou, Xiangman Zou, Xiaosha Wen， Zifen Guo entitled: “Association of PROGINS PgR Polymorphism with susceptibility to female reproductive cancer: A metaanalysis based on 30 studies” The work presented is interesting in terms of demonstrating the association of PROGINS PgR Polymorphism with susceptibility to female reproductive cancer. The manuscript is well written and results are well described with proper statistics. The language is appropriate, technical and easy to read. However, I have some minor recommendations

Comment 1: The highlights of the manuscript should be written properly with more conclusive meaning.

Comment 2: The first sentence of the abstract is not properly written. It should be rewritten with proper meaning.

Comment 3: The first para of introduction section has 2020 data. Update the para with 2021/22 epidemological and incidence data.

Comment 4: In second para of introduction section there are some sentences related to estrogen which creates confusion. Remove the estrogen related sentences or If not rewrite the sentence with proper meaning. Additionally, in second para “vitro” should be replaced with “invitro”

Comment 5: Add some lines about PROGINS and its functions in para 3 of introduction section.

Comment 6: There are various spelling and grammatical mistakes such as “conformed” in materials and methods section. Kindly go through the whole manuscript to edit grammatical mistakes.

Comment 7: Manuscript contains old and outdated references, replace them with latest and updated references wherever possible.

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Reviewer #1: No

Reviewer #2: No

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Association of the PROGINS PgR polymorphism with susceptibility tofemale reproductive cancer: A meta-analysis of 30 studies

PONE-D-21-14829R1

Dear Dr. Guo,

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Kind regards,

Elda Tagliabue

Academic Editor

PLOS ONE

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