Ultra-Trace Blood Concentrations of Blood Serum Arsenic and Breast, Prostate and Colorectal Cancer Risks in the EPIC-Heidelberg Cohort

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The author's submitted manuscript "Ultra-trace blood concentrations of blood serum arsenic and breast, prostate and colorectal cancer risks in the EPIC- Heidelberg Cohort" is a nice and crisp. However my specific comments are below:

1. The author presented their observations in the form of table, the author may present their findings in the form of bar chart so that can easily visualize the relative data presented in the table.
2. The author may provide data related to arsenic level in their food and drinking water as per their demography. 
3. In material and method section, the author didn't mention the methodology of arsenic measurement. 
4. Literature tells about the increased chances of some cancers due to increased arsenic level. However apart from arsenic several other underlying factors also responsible in the development and progression of different types of cancer. Is it possible to design a experiment to identify the possible common link in the samples of the presented data, and show their association with the cancer incidences.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This prospective case–cohort analysis by Kipkoech et al. evaluates associations between ultra-trace serum arsenic concentrations and breast, prostate, and colorectal cancer risks, and overall reports null associations apart from an exploratory protective signal for colon cancer in intermediate arsenic quartiles.

Minor comments:

Emphasize more clearly that serum arsenic reflects recent integrated exposure and may misclassify long-term, low-dose exposure relevant for carcinogenesis; this should be framed as a major limitation rather than a minor one.​

Please discuss in more depth how exclusion of samples below the limit of detection and the chosen LOD threshold may bias associations (e.g., by truncating the lower tail of exposure).

Please provide sensitivity analyses that treat values below detection as LOD/2 or use multiple imputation, and report whether results materially change.

The impact of the study would increase if the authors include additional adjustment or sensitivity analyses including dietary arsenic proxies (e.g., fish, shellfish, rice consumption) to see whether associations are materially altered.

The impact of the study would increase by adding a  histogram or density plot showing the distribution of serum arsenic (overall and by sex) to help readers appreciate the low exposure range and skewness.​

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

A cohort study examined the association between serum arsenic concentration and breast, prostate, and colon cancer. Few studies have addressed this topic to date, making this article worth publishing.

The introduction provides a comprehensive introduction to the topic addressed by the researchers. The aim of the study is stated at the end. The materials and methods include a description of the study protocol, which allows for its reproducibility. The description of the statistical analysis performed is accurate. The results are presented in tables and text. The discussion includes the most important results, which are compared with the results of other studies. Conclusions are drawn appropriately based on the obtained results.

Minor comments:

Materials and methods:

Were the questionnaires standardized and used in other studies? If so, which ones? It's worth describing in detail what topics the study questionnaire covered.

What devices were used for anthropometric measurements?

How was the blood collected? How many milliliters of blood were collected for the study?

Was approval obtained from the Bioethics Committee to conduct the study? Please provide the name of the Bioethics Committee, the number, and the date of the opinion.

What software was used for statistical calculations? Please provide the software name, license, and country.

Discussion: Please add a paragraph describing the implications for the future.

Author Response

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Author Response File: Author Response.pdf