Title: Cruciferous Vegetables Intake and Risk of Colon Cancer: A Dose-Response Meta-
Analysis
Version: 3 Date: 17 Jun 2025
Reviewer's report:
1. If the database search has been updated, please revise the reported date in the manuscript
accordingly. As of now, the Search Strategy section in Materials and Methods still indicates
October 18, 2024, which appears outdated.
2. The full search strategy for each database is not included in the Supplementary Material. To
ensure transparency and reproducibility, please provide the complete search strings used for all
databases in a supplementary appendix.
3. The statement “Due to the low incidence of CC, odds ratios (ORs) from case-control studies
were interpreted as approximating relative risks (RRs)” is methodologically incorrect. The rare
outcome assumption (which allows ORs to approximate RRs) applies only when the prevalence
of the outcome is below 10% in the “studied” population, and more importantly, it is relevant
within individual studies, not at the population level (For instance,  in a case-control study if
the ratio of cases and control are 1:1 the prevalence of outcome (which here is colon cancer) is
50% and if in a study they increase this ratio to 1:3, the prevalence is still 25%. ). Therefore, this
assumption does not apply to case-control studies by design, where RRs cannot be calculated
( OR can be calculated in cohort studies, while RR is more valid effect size for this design). As
previously noted, when combining effect sizes from both cohort and case-control studies, the
summary effect should be reported as an odds ratio (OR).
4. As noted in my previous review comments, reporting the average NOS score is not an
appropriate summary of study quality. Instead, please categorize studies by quality level (e.g.,
low, moderate, high) and provide a brief discussion on the reasons for lower quality scores where
applicable.
5. Line 163: The phrase should be: “an inverse association” (not a inverse).
6. According to my previous recommendation for a subgroup analysis restricted to studies
adjusting for all major confounders: it is acknowledged that studies vary in which confounders
they adjust for. However, a standard and common practice is to use the most adjusted effect
size available in each study, even if the variables included differ. Also, It would be a good idea
to advise future researchers to not only report the crude association, but also report adjusted
effect sizes.
7. Line 287: There appears to be a typographical error in this line. The use of colons (:) seems
redundant.
Title: Cruciferous Vegetables Intake and Risk of Colon Cancer: A Dose-Response Meta-
Analysis
Version: 3 Date: 17 Jun 2025
Reviewer's report:
1. If the database search has been updated, please revise the reported date in the manuscript
accordingly. As of now, the Search Strategy section in Materials and Methods still indicates
October 18, 2024, which appears outdated.
2. The full search strategy for each database is not included in the Supplementary Material. To
ensure transparency and reproducibility, please provide the complete search strings used for all
databases in a supplementary appendix.
3. The statement “Due to the low incidence of CC, odds ratios (ORs) from case-control studies
were interpreted as approximating relative risks (RRs)” is methodologically incorrect. The rare
outcome assumption (which allows ORs to approximate RRs) applies only when the prevalence
of the outcome is below 10% in the “studied” population, and more importantly, it is relevant
within individual studies, not at the population level (For instance,  in a case-control study if
the ratio of cases and control are 1:1 the prevalence of outcome (which here is colon cancer) is
50% and if in a study they increase this ratio to 1:3, the prevalence is still 25%. ). Therefore, this
assumption does not apply to case-control studies by design, where RRs cannot be calculated
( OR can be calculated in cohort studies, while RR is more valid effect size for this design). As
previously noted, when combining effect sizes from both cohort and case-control studies, the
summary effect should be reported as an odds ratio (OR).
4. As noted in my previous review comments, reporting the average NOS score is not an
appropriate summary of study quality. Instead, please categorize studies by quality level (e.g.,
low, moderate, high) and provide a brief discussion on the reasons for lower quality scores where
applicable.
5. Line 163: The phrase should be: “an inverse association” (not a inverse).
6. According to my previous recommendation for a subgroup analysis restricted to studies
adjusting for all major confounders: it is acknowledged that studies vary in which confounders
they adjust for. However, a standard and common practice is to use the most adjusted effect
size available in each study, even if the variables included differ. Also, It would be a good idea
to advise future researchers to not only report the crude association, but also report adjusted
effect sizes.
7. Line 287: There appears to be a typographical error in this line. The use of colons (:) seems
redundant.
Please review this paper.
user
Title: Cruciferous Vegetables Intake and Risk of Colon Cancer: A Dose-Response Meta-
Analysis
Version: 3 Date: 17 Jun 2025
Reviewer's report:
1. If the database search has been updated, please revise the reported date in the manuscript
accordingly. As of now, the Search Strategy section in Materials and Methods still indicates
October 18, 2024, which appears outdated.
2. The full search strategy for each database is not included in the Supplementary Material. To
ensure transparency and reproducibility, please provide the complete search strings used for all
databases in a supplementary appendix.
3. The statement “Due to the low incidence of CC, odds ratios (ORs) from case-control studies
were interpreted as approximating relative risks (RRs)” is methodologically incorrect. The rare
outcome assumption (which allows ORs to approximate RRs) applies only when the prevalence
of the outcome is below 10% in the “studied” population, and more importantly, it is relevant
within individual studies, not at the population level (For instance,  in a case-control study if
the ratio of cases and control are 1:1 the prevalence of outcome (which here is colon cancer) is
50% and if in a study they increase this ratio to 1:3, the prevalence is still 25%. ). Therefore, this
assumption does not apply to case-control studies by design, where RRs cannot be calculated
( OR can be calculated in cohort studies, while RR is more valid effect size for this design). As
previously noted, when combining effect sizes from both cohort and case-control studies, the
summary effect should be reported as an odds ratio (OR).
4. As noted in my previous review comments, reporting the average NOS score is not an
appropriate summary of study quality. Instead, please categorize studies by quality level (e.g.,
low, moderate, high) and provide a brief discussion on the reasons for lower quality scores where
applicable.
5. Line 163: The phrase should be: “an inverse association” (not a inverse).
6. According to my previous recommendation for a subgroup analysis restricted to studies
adjusting for all major confounders: it is acknowledged that studies vary in which confounders
they adjust for. However, a standard and common practice is to use the most adjusted effect
size available in each study, even if the variables included differ. Also, It would be a good idea
to advise future researchers to not only report the crude association, but also report adjusted
effect sizes.
7. Line 287: There appears to be a typographical error in this line. The use of colons (:) seems
redundant.
assistant