Association of missense variant DCLRE1B rs3761936 with breast and cervical cancer risk—A case-control study

Sarah Jafrin; Md. Abdul Aziz; Md Abdul Barek; Md. Sharif Reza; Nura Ershad Naznin; Mohammad Safiqul Islam

doi:10.1371/journal.pone.0331492

Peer Review History

Original SubmissionNovember 8, 2023
11 Mar 2024 Decision Letter - Milad Khorasani, Editor Dear Dr. Islam, 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 submit your revised manuscript by Apr 25 2024 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. 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'. 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Note from Emily Chenette, Editor in Chief of PLOS ONE, and Iain Hrynaszkiewicz, Director of Open Research Solutions at PLOS: Did you know that depositing data in a repository is associated with up to a 25% citation advantage (https://doi.org/10.1371/journal.pone.0230416)? If you’ve not already done so, consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository (https://plos.org/open-science/open-data/#accessible-data). 3. Thank you for stating the following financial disclosure: "The Research Cell, Noakhali Science and Technology University, Noakhali-3814, Bangladesh, funded this study partially (NSTU/RC/20/C-86), and no other public or private logistic funding was provided." Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 4. Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript. 5. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. 6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: This is an interesting paper on the association of missense variant DCLRE1B rs3761936 with breast and cervical cancer. However, due to the design of the study, it is difficult to establish causation, as the authors commented in the discussion The study is based on a researcher-designed interview-administered questionnaire, used to collect the required information. I have not seen any reports on validity and reliability Please highlight the novelty of this study in the conclusions. Discuss the clinical relevance and applicability of the study results locally & globally. Two-sided unpaired t-tests or Independent Samples t Test??? The logistic regression analysis is not well described, specifically with respect to how the multivariable analysis was performed and which variables were selected for inclusion as covariates in the models Describe the variables used in the study in the method section State the inclusion and exclusion criteria of the case and control groups Use more odds than risk in OR interpretation What is missing in the discussion is that the authors should not only compare their studies with similar studies but also discuss the meaning of their findings within the context of the Bangladesh literature, which I think there are a lot. Secondly, the authors need to discuss the policy, practice and research implications of their findings. e.g what does their finding mean regarding the prevention of breast and cervical cancer risk guidelines in Bangladesh? Reviewer #2: These are the following observation: 1. Is it necessary to write The in the starting of the title? I think, word THE is not necessary. 2. The primer of the gene is missing. Please add the primer. 3. Please mention the name of the thermocycler with country of origin. 4. In Table, the authors have mentioned the mean values but without SD. It is mandatory to mention. Please mention SD with each mean values. 5. Statistical analysis is incomplete. Please write according to the analysis. ****** what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy Reviewer #1: No Reviewer #2: Yes: Dr. Md. Abdullah Yusuf ******** [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. Attachments Attachment Submitted filename: PONE-D-23-33713.pdf https://doi.org/10.1371/journal.pone.0331492.r001
Revision 1
17 Apr 2024 Author Response We are thankful to the editor and the reviewers for their crucial comments on our manuscript. We hope these comments will help us improve it. Journal Academic Editor 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: All the requirements are fulfilled as per journal requirements. 2. Consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository. Response: This suggestion is crucial. We have not deposited these data in any repository, but we added our data as an EXCEL file as supporting materials. 3. Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. Response: The statement is included in the Funding information file. 4. Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript. Response: Removed from the manuscript and saved in a ‘financial information’ named file. 5. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. Response: Author information are shared. All the related information will be shared. 6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Response: Done. Reviewer 1 1. Please highlight the novelty of this study in the conclusions. Discuss the clinical relevance and applicability of the study results locally & globally. Response: See the conclusion and discussion section with comments. 2. Two-sided unpaired t-tests or Independent Samples t Test??? The logistic regression analysis is not well described, specifically with respect to how the multivariable analysis was performed and which variables were selected for inclusion as covariates in the models Response: T-tests and other variables are explained in the statistical analysis section. Check comment. 3. Describe the variables used in the study in the method section State the inclusion and exclusion criteria of the case and control groups Response: Done. Inclusion and exclusion criteria are added in the method section. 4. Use more odds than risk in OR interpretation Response: Resolved the issue 5. What is missing in the discussion is that the authors should not only compare their studies with similar studies but also discuss the meaning of their findings within the context of the Bangladesh literature, which I think there are a lot. Secondly, the authors need to discuss the policy, practice and research implications of their findings. e.g what does their finding mean regarding the prevention of breast and cervical cancer risk guidelines in Bangladesh? Response: Added more information in relation to Bangladeshi BC and CC cancer guidelines. Tried to explain all the points as suggested. Please see the comment section of the discussion. Reviewer 2 1. Is it necessary to write The in the starting of the title? I think, word THE is not necessary. Response: ‘The’ is removed from the title. 2. The primer of the gene is missing. Please add the primer. Response: Please check the supporting table 1. 3. Please mention the name of the thermocycler with country of origin. Response: Mentioned in the method section. 4. In Table, the authors have mentioned the mean values but without SD. It is mandatory to mention. Please mention SD with each mean values Response: SD values are added to the mean values. Check Table 2. 5. Statistical analysis is incomplete. Please write according to the analysis. Response: Statistical analysis is explained as suggested according to the analysis. Attachments Attachment Submitted filename: Response.docx https://doi.org/10.1371/journal.pone.0331492.r002
23 Jun 2024 Decision Letter - Milad Khorasani, Editor Dear Dr. Islam, 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 submit your revised manuscript by Aug 07 2024 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. 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Milad Khorasani, PhD Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: (No Response) Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: Yes Reviewer #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: No Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: (No Response) Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: (No Response) Reviewer #2: Yes ****** Reviewer #1: Dear Editor My comments 1, 4, and 5 have not been answered Also, track changes or highlight the responses to the reviewer's comments Reviewer #2: The authors have tested less number of control than case group. How they match this? The propensity scoring analysis is missing to compare the group. It is very difficult to say that there is a genetic association unless otherwise properly matched the 2 groups. Please explain why this happen. The methodology section is poorly mentioned about the procedure of the genetic tests. Explain in details. The discussion section needs more elaboration before concretely said that there is a genetic association. ****** what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy Reviewer #1: No Reviewer #2: Yes: Dr. Md. Abdullah Yusuf ******** [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. https://doi.org/10.1371/journal.pone.0331492.r003
Revision 2
25 Jul 2025 Author Response PONE-D-23-33713R1 Association of missense variant DCLRE1B rs3761936 with breast and cervical cancer risk - A case-control study We are thankful to the editor and the reviewers for their crucial comments on our manuscript. We hope these comments will help us improve it. Reviewer 1 My comments 1, 4, and 5 have not been answered Also, track changes or highlight the responses to the reviewer's comments. Response: All the comments by the reviewer were considered and revised accordingly. Please see the track changes and comments of the edited manuscript with track changes. Reviewer 2 The authors have tested less number of control than case group. How they match this? The propensity scoring analysis is missing to compare the group. It is very difficult to say that there is a genetic association unless otherwise properly matched the 2 groups. Please explain why this happen. The methodology section is poorly mentioned about the procedure of the genetic tests. Explain in detail. The discussion section needs more elaboration before concretely said that there is a genetic association. Response: Reviewer 2 The authors have tested less number of control than case group. How they match this? The propensity scoring analysis is missing to compare the group. It is very difficult to say that there is a genetic association unless otherwise properly matched the 2 groups. Please explain why this happen. The methodology section is poorly mentioned about the procedure of the genetic tests. Explain in detail. The discussion section needs more elaboration before concretely said that there is a genetic association. Response: We used a single control group (108) for two case groups (135 BC and 110 CC). Due to COVID-19 pandemic situation, our control sample collection was limited. Although we tested less number of controls against the case groups during genetic association analysis, we maintained the ratios within the acceptable range and heterogeneity, along with other statistical variables were significantly controlled. Valid estimates of the odds were obtained by following appropriate sample selection processes. The variant under investigation is inherited from parents, so an individual’s genotype is set at conception and is generally independent of lifestyle or socio‑demographic characteristics. Because such germline alleles are passed down randomly, they are not expected to correlate with non‑genetic confounders. For this reason, propensity‑score matching is rarely applied in genetic case–control research and is not yet a routine tool for controlling confounding in this field. Instead, we accounted for potential differences between cases and controls in age and other risk factors using multivariable logistic regression models. This widely accepted approach preserves statistical power and avoids the information loss that can occur when matching on many variables. We add a statement regarding this before the conclusion section in the manuscript. The methodology section is properly explained as per the reviewer’s suggestion. Please see the Methodology section of the revised manuscript. (Highlighted portion) The Discussion section is elaborated as per the reviewer’s comment. (Highlighted portion) Attachments Attachment Submitted filename: Reviewers comments and Author response.docx https://doi.org/10.1371/journal.pone.0331492.r004
18 Aug 2025 Decision Letter - Milad Khorasani, Editor Association of missense variant DCLRE1B rs3761936 with breast and cervical cancer risk - A case-control study PONE-D-23-33713R2 Dear Dr. Safiqul Islam, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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. Kind regards, Milad Khorasani, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes ****** Reviewer #2: The correction are properly done, however, the comparison of case and control group values should be compared and the p values are missing in the tables. ****** what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy Reviewer #2: Yes: Md Abdullah Yusuf ******** https://doi.org/10.1371/journal.pone.0331492.r005
Formally Accepted
Acceptance Letter - Milad Khorasani, Editor PONE-D-23-33713R2 PLOS ONE Dear Dr. Islam, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Milad Khorasani Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0331492.r006

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