PONE-D-20-10549

Occupational Bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes.

PLOS ONE

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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

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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5. 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: The submitted manuscript “Occupational Bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes.” by Reed et al. reports on 454 patients with urothelial bladder cancer, first diagnosed and treated between 02/2010 - 07/2012 at a single institution, the RHH (Sheffield).

Based on a patient-reported questionnaire, patients were evaluated for potential carcinogen exposure, whilst occupational classes were assigned using NYK and ISCO-1958 codes.

With a median follow-up of 8.4 years, the authors additionally report on tumor progression and the need of radical intervention. Outcome data was collected between 08/2018 - 10/2018.

This questionnaire-based evaluation, revealed multiple occupational tasks and contacts associated with high grade and high stage BC. Tumors were classified according to TNM and WHO 1973 criteria, therefore G1-G3 grading data has been reported.

Typical for an urothelial cancer population is the distribution between men and women with a ratio of roughly 4:1. Therefore, the reported data refers to mainly men, since all patients were included at time of initial diagnosis of bladder cancer.

The authors found differences in exposures between men and women, including

distinct patterns of employment, differences in smoking rates and patterns,

hair dye use and hobbies.

When only female patients were analyzed, the data suggests an association between high grade/high stage BC and workers undertaking electroplating and cutlery manufacture, and tasks such as degreasing and painting.

Although, the included patient cohort quite small to evaluate potential influences of exposure to occupational carcinogens, there are some interesting findings, worth to be reported.

Limitations of the manuscript are well described (e.g. estimated duration of each task), data reported and analyzed with appropriate methods, and outcome data revealed quite distinct differences for specific occupational groups.

Overall, an interesting and well-written manuscript, worth publication after minor revision:

Some comments:

- Please use BOLD for all significant values, which makes it easier to read tables.

- For Kaplan-Meier curves, please add “at risk numbers” on the bottom of the graphs.

Reviewer #2: Paper Occupational bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes by dr. Reed et al.

Very interesting study. I have just few comments, which, as I believe, can improve paper.

1, I would stress time of exposure. I believe it is very important point missed in discussion and even in abstract

2, I would suggest also hobby of participants. It is well known from other epidemiological studies......example can be psittacosis. It is indeed mostly occupational exposure linked disease, however substantial part of patients came from hobby sector (bird breeders, parrot lovers, etc, etc). Authors listed garage work as potential risk factor for aggressive disease course with recquired radical treatment. There are many car lovers, bikers who spend a substantial time in care of their gear and indeed they are haevily exposed to risk substanties. I think this should be at least discussed.

3, Is there any chance to check any link between variant histology (mostly highly aggressive tumors, sometimes with bland cytology-ie LG, like nested UC) and occupational exposure

Thank you

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PLOS one occupational.docx

Occupational Bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes.

PONE-D-20-10549R1

Dear Dr. Reed,

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,

Amitava Mukherjee, ME, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: All comments have been addressed

Reviewer #2: All comments have been addressed

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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

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: The authors have addressed the comments made by the reviewers and changed their manuscript accrodingly.

Reviewer #2: I believe this paper can help to solve questions about potential agents playing etiological role in development of UC. I do not have any further questions. Thank you

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7. PLOS authors have the option to publish the peer review history of their article (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: No