Peer Review History

Original SubmissionAugust 18, 2020

Attachments
Attachment
Submitted filename: Response_to_Editor_PONE-D-20-23035.docx
Decision Letter - Zhongxue Chen, Editor

PONE-D-20-23035

Statistical meta-analysis to investigate the association between interleukin-6 gene polymorphisms and cancer risk

PLOS ONE

Dear Dr. Mollah,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

In the manuscript, the authors performed meta-analyses with large sample sizes. The findings, if based on appropriate statistical methods, from this study may provide us useful information in the area. However, when you apply "standard" meta-analysis models (e.g., fixed and random effect models), you need to check the fit of the models; otherwise, the outputs from inadequate models might be misleading. Please perform goodness of fit tests for your models. You can use the gof tests described in the following reference: Chen, Z., Zhang, G., & Li, J. (2015). Goodness-of-fit test for meta-analysis. Scientific reports, 5, 16983. If indeed your models are lack of fit, please revise your paper accordingly (e.g., you can follow the suggestions offered in the above mentioned reference). After receiving your revised manuscript, I will be happy to reconsider your manuscript for possible publication.

Please submit your revised manuscript by Nov 05 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Zhongxue Chen

Academic Editor

PLOS ONE

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Reviewers' comments:

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Revision 1

Response to Review Comments

Review Comments: Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

In the manuscript, the authors performed meta-analyses with large sample sizes. The findings, if based on appropriate statistical methods, from this study may provide us useful information in the area. However, when you apply "standard" meta-analysis models (e.g., fixed and random effect models), you need to check the fit of the models; otherwise, the outputs from inadequate models might be misleading. Please perform goodness of fit tests for your models. You can use the gof tests described in the following reference: Chen, Z., Zhang, G., & Li, J. (2015). Goodness-of-fit test for meta-analysis. Scientific reports, 5, 16983. If indeed your models are lack of fit, please revise your paper accordingly (e.g., you can follow the suggestions offered in the above mentioned reference). After receiving your revised manuscript, I will be happy to reconsider your manuscript for possible publication.

Author’s response: Thank you very much for your kind suggestion. We revised our manuscript accordingly. At first, we introduced the importance GoF test in the last paragraph of introduction section (page 4, highlighted portion with blue color). Then we provided the short summary of GoF test in the materials and methods section (pages 13-14, highlighted portion with blue color). We observed that in some cases GoF test based fitted models contradicts with the fitted models based on Cochran’s homogeneity test and changes the previous decision about the association between gene polymorphisms and cancer risks. In particularly, we observed the changes with some overall and subgroup cases of all polymorphisms (rs1800795, rs1800796, rs1800797). For example,

• For rs1800795, the contradictory model were observed for overall cases and Caucasian ethnic group under two genetic combinations (CC + CG vs. GG; CG vs. CC + GG); blood, liver, skin and stomach cancer under all genetic combinations (CC vs. GG; CC vs. CG + GG; CC + CG vs. GG; CG vs. CC + GG; C vs. G); breast cancer under three genetic combinations (CC vs. GG; CC vs. CG + GG; CG vs. CC + GG); colon cancer (CC vs. CG + GG), lung cancer (CC vs. GG; CC + CG vs. GG); prostate cancer (CG vs. CC + GG); Asian ethnic group under four genetic combinations (CC vs. CG + GG; CC + CG vs. GG; CG vs. CC + GG; C vs. G) (Please see additional file ‘S1 Table’, Highlighted portion with blue color). The significant association were changed in the case of liver cancer (CG vs. CC + GG) (Table 2, page 13, highlighted portion with blue color) and Asian ethnicity (CC + CG vs. GG and C vs. G) (Table 2, page 17, highlighted portion with bold & blue color).

• For rs1800796, the contradictory model were observed for the case of colon cancer under three genetic combinations (CC vs. CG + GG; CC + CG vs. GG; CG vs. CC + GG); prostate and stomach cancer for all genetic combinations (CC vs. GG; CC vs. CG + GG; CC + CG vs. GG; CG vs. CC + GG; C vs. G); Caucasian populations (CC vs. GG; CC vs. CG + GG) (Please see additional file ‘S1 Table’, Highlighted portion with blue color). The significant association were changed only the case of stomach cancer (CC + CG vs. GG) (Table 3, page-18, highlighted portion with bold & blue color).

• For rs1800797, the contradictory model were observed for the case of overall cancer under two genetic combinations (CC vs. GG; CC vs. CG + GG); and Caucasian populations under all genetic combinations (CC vs. GG; CC vs. CG + GG; CC + CG vs. GG; CG vs. CC + GG; C vs. G) (Please see additional file ‘S1 Table’, Highlighted portion with blue color). There were no significant association changes were observed (Table 3, page-19).

We also updated the discussion and conclusion section based on the revised manuscript (page 24-25, highlighted with blue color)

Reference: Chen, Z., Zhang, G., & Li, J. (2015). Goodness-of-fit test for meta-analysis., Scientific reports, 5, 16983)

Attachments
Attachment
Submitted filename: Response to Reviwers_PONE-D-20-23035.docx
Decision Letter - Zhongxue Chen, Editor

PONE-D-20-23035R1

Statistical meta-analysis to investigate the association between interleukin-6 gene polymorphisms and cancer risk

PLOS ONE

Dear Dr. Mollah,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please pay special attention to the reference list, there were several replicates.

Please submit your revised manuscript by Mar 01 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Zhongxue Chen

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: No

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to review this manuscript. This is a well-conducted meta-analysis that thoroughly analyzed the associations between these three IL6 SNPs and cancer risk. I have a few minor comments:

1. This manuscript could benefit from some proofreading by a native English speaker, as there are a number of grammatical errors throughout the paper. In particular, the phrase "IL-6 gene" needs to have the word "the" preceding it, or it can be replaced by "IL6" in italics without the word "the" to refer to the gene itself.

2. Are the studies listed in Table 1 in any particular order within each SNP? If so, this should be included as a footnote. If not, I would recommend putting them in some order that would make it easier for the reader to review.

3. In Tables 2-4, add footnotes indicating that the ORs for the ethnicity subgroups are for overall cancer risk. Similarly, specify in the methods/results/discussion that the models are estimating overall cancer risk within each ethnicity subgroup.

4. In Table 4, there is a typographical error for the OR for breast cancer in the column for CG vs. CC + GG. There is a space missing between the OR and the CI: 0.98[0.91; 1.04]

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Reviewer #1: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 2

Dear Professor Zhongxue Chen

Academic Editor, PLOS ONE

Thank you very much for giving us the opportunity to re-revise our manuscript (ID: PONE-D-20-23035R1) according to the reviewer comments for possible publication in PLOS ONE. We revised our manuscript accordingly as follows:

Reviewer #1 General Comments: Thank you for the opportunity to review this manuscript. This is a well-conducted meta-analysis that thoroughly analyzed the associations between these three IL6 SNPs and cancer risk. I have a few minor comments:

Minor comments-1: This manuscript could benefit from some proofreading by a native English speaker, as there are a number of grammatical errors throughout the paper. In particular, the phrase "IL-6 gene" needs to have the word "the" preceding it, or it can be replaced by "IL6" in italics without the word "the" to refer to the gene itself.

Author’s response: Thanks for your kind suggestion, we tried to revise the manuscript accordingly and replaced “IL-6 gene” by the “the IL-6 gene” throughout the manuscript (Highlighted by Track changes).

Minor comments-2: Are the studies listed in Table 1 in any particular order within each SNP? If so, this should be included as a footnote. If not, I would recommend putting them in some order that would make it easier for the reader to review.

Author’s response: Yes, the studies listed in Table 1were ordered according to the year of publication for individual SNPs (Table 1, pages 5-8). Also, we added a footnote for the reader’s convenience (Table 1, page 8, Highlighted by Track changes). Thank you so much for the suggestions and going through in that detail.

Minor comments-3: In Tables 2-4, add footnotes indicating that the ORs for the ethnicity subgroups are for overall cancer risk. Similarly, specify in the methods/results/discussion that the models are estimating overall cancer risk within each ethnicity subgroup.

Author’s response: Thanks again you for your suggestions about Tables 2-4.We updated Tables 2-4 accordingly and added footnote with each table to indicate that the ORs for the ethnicity subgroups are for overall cancer risk (Table 2, page 16; Table 3, page 17; Table 4, page 18; Highlighted by Track changes). We also specified this issue in the results and discussion section of the manuscript (Pages 19, 21-24).

Minor comments-4: In Table 4, there is a typographical error for the OR for breast cancer in the column for CG vs. CC + GG. There is a space missing between the OR and the CI: 0.98[0.91; 1.04]

Author’s response: Thank you so much for your comments. This error was found in Table 2 and we updated it carefully (Table 2, page 16; Highlighted by Track changes).

Attachments
Attachment
Submitted filename: Respone to Reviewers_PONE-D-20-23035R2.docx
Decision Letter - Zhongxue Chen, Editor

Statistical meta-analysis to investigate the association between the interleukin-6 (IL-6) gene polymorphisms and cancer risk

PONE-D-20-23035R2

Dear Dr. Mollah,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Zhongxue Chen

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Zhongxue Chen, Editor

PONE-D-20-23035R2

Statistical meta-analysis to investigate the association between the Interleukin-6 (IL-6) gene polymorphisms and cancer risk

Dear Dr. Mollah:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Zhongxue Chen

Academic Editor

PLOS ONE

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