Title: Cruciferous Vegetables Intake and Risk of Colon Cancer: A Dose-Response Meta-
Analysis
Version: 2 Date: 02 May 2025
Reviewer's report:
1. There are several writing errors throughout the manuscript, a careful proofread is suggested.
Title:
2. Please revise the title to: “A dose–response meta analysis.”
Abstract
3. Replace the phrase “colon cancer (CC) risk reduction” with “risk of colon cancer (CC).”
4. In the Methods subsection, identify the specific risk#of#bias (ROB) tool applied and state
the statistical approaches used to evaluate publication bias. Also mention whether any subgroup
analysis or sensitivity analysis were conducted.
5. The Conclusion is expressed too definitively; please temper the language by acknowledging
the study’s limitations.
Introduction
6. Spell out each term in full at first mention—e.g., colon cancer (CC) and Cruciferous
consumption (CV)—and use the abbreviations thereafter.
7. Rephrase the sentence “The association between CV and CC has been studied …” to:
8. “The association between CV consumption (or intake) and CC has been studied …”
9. Move the sentence “We present this article in accordance with the PRISMA checklist” to the
Materials and Methods section, immediately before the Search strategy subsection. Specify the
version of the PRISMA checklist used and provide the appropriate citation.
Materials and methods
10. In line with Cochrane guidance, more than 6 months have passed since the database search;
please update the search to capture newly published studies.
11. Because the Cochrane Library mainly indexes interventional and diagnostic#accuracy
studies, and this review evaluates an exposure–outcome relationship, add Scopus to the database
search.
12. PRISMA requires the full, reproducible search strategies for every database. Provide the
search strategy of each database in the Supplementary Material.
13. Present inclusion and exclusion criteria using the PECOS framework (Population, Exposure,
Comparator, Outcomes, and Study design.)
14. Give a brief description of each domain of the Newcastle–Ottawa Scale (NOS) and explain
how total scores are calculated.
15. When combining relative risks (RRs) and odds ratios (ORs), report the summary effect as
an OR. (since this emphasize that ORs inherently overstate effect sizes, warranting cautious
interpretation.)
16. Select between fixed# and random#effects models primarily on the basis of methodological
heterogeneity. Relying on the I² statistic is methodologically incorrect, as it’s an indicator of
statistical, not methodological, heterogeneity.
17. State the estimator used for between#study variance (#²) (e.g., DerSimonian–Laird, restricted
maximum likelihood and ….).
18. In the sentence “the random#effects model was also employed due to its careful
methodology,” replace “careful” with “conservative.”
19. Instead of applying both Begg’s and Egger’s tests, use Egger’s test (due to it’s conservative
approach) in conjunction with funnel or Doi plots and the LFK index.
20. For open-ended categories, by using this technique (The intake dose for open intervals was
calculated by dividing the interval's endpoint by 1.2) shifts the value back toward the previous
category. I think the correct approach should be the Multiplying the interval's endpoint by 1.2.
21. Expand the statistical description of dose-response model. explain the criteria used
to choose between linear and non#linear dose–response functions and, in addition to the
restricted cubic#spline model, present other models such as linear regression and quadratic
(natural#polynomial) models.
Results
22. The very small number of records retrieved suggests an exclusive search strategy! Please
first supply the complete search strings for every database in the Supplementary Material and
secondly include Scopus, a multidisciplinary database with broad journal coverage (as my
previous comments in methods section).
23. Figure#1 does not conform to the PRISMA flow#diagram template; redraw it in the standard
format.
24. Replace “Oceania” with “Australia.”
25. Lines#127–128—delete the second occurrence of “questionnaires” in “validated
food#frequency questionnaires or questionnaires.”
26. Create a separate subsection for study quality (Risk of Bias). Also, Reporting the average
score of studies from NOS tool is not appropriate (line number 130). Instead mention the number
of studies in each category and discuss about the reasons of low quality.
27. Because relative risks (RRs) and odds ratios (ORs) are pooled, the combined effect size
should be an OR. Update all texts, figures and tables.
28. This sentence is unclear (With a CV intake of the greatest (RR = 0.83; 95% CI: 0.59-1.18),
the incidence of CC was 17% lower than that with the lowest intake. ) and I suggest to be
rephrased to "The highest category of CV intake was associated with a 17% lower incidence of
CC compared to the lowest intake group (RR = 0.83; 95% CI: 0.59–1.18)."
29. Report the pooled effect per exposure increment (e.g., per 1#g/day increase in CV) for each
section of non-linear model, the regression coefficient for each section of non-linear model, and
fitness such as the Akaike information criterion (AIC).
30. Clarify what the P#value column represents. If these are P#values for the pooled estimates,
they appear inconsistent with the stated confidence intervals.
31. In Table#2, Change “Family for CC” to “Family history of CC.”
32. Conduct a subgroup analysis restricted to studies that adjust for all major confounders; this
will help to reach the more pure exposure–outcome association.
33. The leave#one#out analysis indicates that no single study considerably changes the pooled
estimate; revise the interpretation in lines#153–154 to reflect this finding.
Discussion
34. The statement “there is strong evidence that consuming more CV may reduce the risk of CC”
is overly definitive, given that most included studies are case–control designs and substantial
heterogeneity was present. Temper the language to reflect the observational nature and the
inconsistency of the evidence base.
35. The mechanistic citations for CV (dated 1983 and 2001) are outdated (last references). Please
replace or supplement them with more recent studies.
36. Methods for publication bias assessment can be further strengthened, so it can not be stated
as a strength ( line number 202 to 204). Consider strengthening the assessment (e.g., Doi plots
with LFK index) or re#classifying it as a limitation.
37. In the discussion section more attention should be made on limitations of study in order to
help readers give appropriate insights. Also give points for future researcher.
Title: Cruciferous Vegetables Intake and Risk of Colon Cancer: A Dose-Response Meta-
Analysis
Version: 2 Date: 02 May 2025
Reviewer's report:
1. There are several writing errors throughout the manuscript, a careful proofread is suggested.
Title:
2. Please revise the title to: “A dose–response meta analysis.”
Abstract
3. Replace the phrase “colon cancer (CC) risk reduction” with “risk of colon cancer (CC).”
4. In the Methods subsection, identify the specific risk#of#bias (ROB) tool applied and state
the statistical approaches used to evaluate publication bias. Also mention whether any subgroup
analysis or sensitivity analysis were conducted.
5. The Conclusion is expressed too definitively; please temper the language by acknowledging
the study’s limitations.
Introduction
6. Spell out each term in full at first mention—e.g., colon cancer (CC) and Cruciferous
consumption (CV)—and use the abbreviations thereafter.
7. Rephrase the sentence “The association between CV and CC has been studied …” to:
8. “The association between CV consumption (or intake) and CC has been studied …”
9. Move the sentence “We present this article in accordance with the PRISMA checklist” to the
Materials and Methods section, immediately before the Search strategy subsection. Specify the
version of the PRISMA checklist used and provide the appropriate citation.
Materials and methods
10. In line with Cochrane guidance, more than 6 months have passed since the database search;
please update the search to capture newly published studies.
11. Because the Cochrane Library mainly indexes interventional and diagnostic#accuracy
studies, and this review evaluates an exposure–outcome relationship, add Scopus to the database
search.
12. PRISMA requires the full, reproducible search strategies for every database. Provide the
search strategy of each database in the Supplementary Material.
13. Present inclusion and exclusion criteria using the PECOS framework (Population, Exposure,
Comparator, Outcomes, and Study design.)
14. Give a brief description of each domain of the Newcastle–Ottawa Scale (NOS) and explain
how total scores are calculated.
15. When combining relative risks (RRs) and odds ratios (ORs), report the summary effect as
an OR. (since this emphasize that ORs inherently overstate effect sizes, warranting cautious
interpretation.)
16. Select between fixed# and random#effects models primarily on the basis of methodological
heterogeneity. Relying on the I² statistic is methodologically incorrect, as it’s an indicator of
statistical, not methodological, heterogeneity.
17. State the estimator used for between#study variance (#²) (e.g., DerSimonian–Laird, restricted
maximum likelihood and ….).
18. In the sentence “the random#effects model was also employed due to its careful
methodology,” replace “careful” with “conservative.”
19. Instead of applying both Begg’s and Egger’s tests, use Egger’s test (due to it’s conservative
approach) in conjunction with funnel or Doi plots and the LFK index.
20. For open-ended categories, by using this technique (The intake dose for open intervals was
calculated by dividing the interval's endpoint by 1.2) shifts the value back toward the previous
category. I think the correct approach should be the Multiplying the interval's endpoint by 1.2.
21. Expand the statistical description of dose-response model. explain the criteria used
to choose between linear and non#linear dose–response functions and, in addition to the
restricted cubic#spline model, present other models such as linear regression and quadratic
(natural#polynomial) models.
Results
22. The very small number of records retrieved suggests an exclusive search strategy! Please
first supply the complete search strings for every database in the Supplementary Material and
secondly include Scopus, a multidisciplinary database with broad journal coverage (as my
previous comments in methods section).
23. Figure#1 does not conform to the PRISMA flow#diagram template; redraw it in the standard
format.
24. Replace “Oceania” with “Australia.”
25. Lines#127–128—delete the second occurrence of “questionnaires” in “validated
food#frequency questionnaires or questionnaires.”
26. Create a separate subsection for study quality (Risk of Bias). Also, Reporting the average
score of studies from NOS tool is not appropriate (line number 130). Instead mention the number
of studies in each category and discuss about the reasons of low quality.
27. Because relative risks (RRs) and odds ratios (ORs) are pooled, the combined effect size
should be an OR. Update all texts, figures and tables.
28. This sentence is unclear (With a CV intake of the greatest (RR = 0.83; 95% CI: 0.59-1.18),
the incidence of CC was 17% lower than that with the lowest intake. ) and I suggest to be
rephrased to "The highest category of CV intake was associated with a 17% lower incidence of
CC compared to the lowest intake group (RR = 0.83; 95% CI: 0.59–1.18)."
29. Report the pooled effect per exposure increment (e.g., per 1#g/day increase in CV) for each
section of non-linear model, the regression coefficient for each section of non-linear model, and
fitness such as the Akaike information criterion (AIC).
30. Clarify what the P#value column represents. If these are P#values for the pooled estimates,
they appear inconsistent with the stated confidence intervals.
31. In Table#2, Change “Family for CC” to “Family history of CC.”
32. Conduct a subgroup analysis restricted to studies that adjust for all major confounders; this
will help to reach the more pure exposure–outcome association.
33. The leave#one#out analysis indicates that no single study considerably changes the pooled
estimate; revise the interpretation in lines#153–154 to reflect this finding.
Discussion
34. The statement “there is strong evidence that consuming more CV may reduce the risk of CC”
is overly definitive, given that most included studies are case–control designs and substantial
heterogeneity was present. Temper the language to reflect the observational nature and the
inconsistency of the evidence base.
35. The mechanistic citations for CV (dated 1983 and 2001) are outdated (last references). Please
replace or supplement them with more recent studies.
36. Methods for publication bias assessment can be further strengthened, so it can not be stated
as a strength ( line number 202 to 204). Consider strengthening the assessment (e.g., Doi plots
with LFK index) or re#classifying it as a limitation.
37. In the discussion section more attention should be made on limitations of study in order to
help readers give appropriate insights. Also give points for future researcher.
Please review this paper.
user
Title: Cruciferous Vegetables Intake and Risk of Colon Cancer: A Dose-Response Meta-
Analysis
Version: 2 Date: 02 May 2025
Reviewer's report:
1. There are several writing errors throughout the manuscript, a careful proofread is suggested.
Title:
2. Please revise the title to: “A dose–response meta analysis.”
Abstract
3. Replace the phrase “colon cancer (CC) risk reduction” with “risk of colon cancer (CC).”
4. In the Methods subsection, identify the specific risk#of#bias (ROB) tool applied and state
the statistical approaches used to evaluate publication bias. Also mention whether any subgroup
analysis or sensitivity analysis were conducted.
5. The Conclusion is expressed too definitively; please temper the language by acknowledging
the study’s limitations.
Introduction
6. Spell out each term in full at first mention—e.g., colon cancer (CC) and Cruciferous
consumption (CV)—and use the abbreviations thereafter.
7. Rephrase the sentence “The association between CV and CC has been studied …” to:
8. “The association between CV consumption (or intake) and CC has been studied …”
9. Move the sentence “We present this article in accordance with the PRISMA checklist” to the
Materials and Methods section, immediately before the Search strategy subsection. Specify the
version of the PRISMA checklist used and provide the appropriate citation.
Materials and methods
10. In line with Cochrane guidance, more than 6 months have passed since the database search;
please update the search to capture newly published studies.
11. Because the Cochrane Library mainly indexes interventional and diagnostic#accuracy
studies, and this review evaluates an exposure–outcome relationship, add Scopus to the database
search.
12. PRISMA requires the full, reproducible search strategies for every database. Provide the
search strategy of each database in the Supplementary Material.
13. Present inclusion and exclusion criteria using the PECOS framework (Population, Exposure,
Comparator, Outcomes, and Study design.)
14. Give a brief description of each domain of the Newcastle–Ottawa Scale (NOS) and explain
how total scores are calculated.
15. When combining relative risks (RRs) and odds ratios (ORs), report the summary effect as
an OR. (since this emphasize that ORs inherently overstate effect sizes, warranting cautious
interpretation.)
16. Select between fixed# and random#effects models primarily on the basis of methodological
heterogeneity. Relying on the I² statistic is methodologically incorrect, as it’s an indicator of
statistical, not methodological, heterogeneity.
17. State the estimator used for between#study variance (#²) (e.g., DerSimonian–Laird, restricted
maximum likelihood and ….).
18. In the sentence “the random#effects model was also employed due to its careful
methodology,” replace “careful” with “conservative.”
19. Instead of applying both Begg’s and Egger’s tests, use Egger’s test (due to it’s conservative
approach) in conjunction with funnel or Doi plots and the LFK index.
20. For open-ended categories, by using this technique (The intake dose for open intervals was
calculated by dividing the interval's endpoint by 1.2) shifts the value back toward the previous
category. I think the correct approach should be the Multiplying the interval's endpoint by 1.2.
21. Expand the statistical description of dose-response model. explain the criteria used
to choose between linear and non#linear dose–response functions and, in addition to the
restricted cubic#spline model, present other models such as linear regression and quadratic
(natural#polynomial) models.
Results
22. The very small number of records retrieved suggests an exclusive search strategy! Please
first supply the complete search strings for every database in the Supplementary Material and
secondly include Scopus, a multidisciplinary database with broad journal coverage (as my
previous comments in methods section).
23. Figure#1 does not conform to the PRISMA flow#diagram template; redraw it in the standard
format.
24. Replace “Oceania” with “Australia.”
25. Lines#127–128—delete the second occurrence of “questionnaires” in “validated
food#frequency questionnaires or questionnaires.”
26. Create a separate subsection for study quality (Risk of Bias). Also, Reporting the average
score of studies from NOS tool is not appropriate (line number 130). Instead mention the number
of studies in each category and discuss about the reasons of low quality.
27. Because relative risks (RRs) and odds ratios (ORs) are pooled, the combined effect size
should be an OR. Update all texts, figures and tables.
28. This sentence is unclear (With a CV intake of the greatest (RR = 0.83; 95% CI: 0.59-1.18),
the incidence of CC was 17% lower than that with the lowest intake. ) and I suggest to be
rephrased to "The highest category of CV intake was associated with a 17% lower incidence of
CC compared to the lowest intake group (RR = 0.83; 95% CI: 0.59–1.18)."
29. Report the pooled effect per exposure increment (e.g., per 1#g/day increase in CV) for each
section of non-linear model, the regression coefficient for each section of non-linear model, and
fitness such as the Akaike information criterion (AIC).
30. Clarify what the P#value column represents. If these are P#values for the pooled estimates,
they appear inconsistent with the stated confidence intervals.
31. In Table#2, Change “Family for CC” to “Family history of CC.”
32. Conduct a subgroup analysis restricted to studies that adjust for all major confounders; this
will help to reach the more pure exposure–outcome association.
33. The leave#one#out analysis indicates that no single study considerably changes the pooled
estimate; revise the interpretation in lines#153–154 to reflect this finding.
Discussion
34. The statement “there is strong evidence that consuming more CV may reduce the risk of CC”
is overly definitive, given that most included studies are case–control designs and substantial
heterogeneity was present. Temper the language to reflect the observational nature and the
inconsistency of the evidence base.
35. The mechanistic citations for CV (dated 1983 and 2001) are outdated (last references). Please
replace or supplement them with more recent studies.
36. Methods for publication bias assessment can be further strengthened, so it can not be stated
as a strength ( line number 202 to 204). Consider strengthening the assessment (e.g., Doi plots
with LFK index) or re#classifying it as a limitation.
37. In the discussion section more attention should be made on limitations of study in order to
help readers give appropriate insights. Also give points for future researcher.
assistant