Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 3 Date: 24 Jan 2025
Reviewer's report:
Luo J et al investigated the associations of a novel biomarker, red blood cell distribution width-
to-albumin ratio, with CRC and GC risk. They further used MR techniques to partially validate
their findings from the observation study. This is well- written. However, my concerns are shown
below:
Introduction:
1. NLP and PLR have limited sensitivity and specificity and are predominantly used for
prognostic prediction. Can RAR bridge these gaps? To my knowledge, no studies investigated
the associations of NLP and PLR and CRC/GC risk. We do not know their roles in risk
prediction.
2. Summarize the current literature on the topics of RAR/RDW/albumin and CRC/GC risk.
Method:
1. Included inclusion and exclusion criteria in the Method section. Did you remove the
individuals with cancer diagnosis before the enrollment? I have concerns about the reverse
causation.
2. RAR was calculated already in NHANES dataset? If no, mention how you computed this
biomarker. Also, add unit for albumin.
3. You mentioned trend and interaction analysis in the Results section. Add more details in
Method section. Which test did you use for interaction analysis, likelihood ratio or Wald test?
For trend analysis, you used median value of each quartile or treating them as an ordinal variable.
4. Some sensitive analyses are necessary if data are available. (1) among aspirin nonuser group;
(2) among participants with cancer diagnosis of 2 year after enrollment; (3) performed multiple
imputation on covariate missing data.
5. MR did not fully support your results. Your main aim is to assess the associations between
RAR and CRC/GC risk among diverse populations. However, GWAS summary statistics for
RAR and other ancestry groups is not available. You assessed albumin and RDW among
European Ancestry. Several papers were published and identified the inverse associations. What
differences between yours and the previous study? Also, you did not assess GC risk.
Results:
1. How many participants with albumin lying outside the clinically normal range? How many
participants with RDW lying outside the clinically normal range?
Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 3 Date: 24 Jan 2025
Reviewer's report:
Luo J et al investigated the associations of a novel biomarker, red blood cell distribution width-
to-albumin ratio, with CRC and GC risk. They further used MR techniques to partially validate
their findings from the observation study. This is well- written. However, my concerns are shown
below:
Introduction:
1. NLP and PLR have limited sensitivity and specificity and are predominantly used for
prognostic prediction. Can RAR bridge these gaps? To my knowledge, no studies investigated
the associations of NLP and PLR and CRC/GC risk. We do not know their roles in risk
prediction.
2. Summarize the current literature on the topics of RAR/RDW/albumin and CRC/GC risk.
Method:
1. Included inclusion and exclusion criteria in the Method section. Did you remove the
individuals with cancer diagnosis before the enrollment? I have concerns about the reverse
causation.
2. RAR was calculated already in NHANES dataset? If no, mention how you computed this
biomarker. Also, add unit for albumin.
3. You mentioned trend and interaction analysis in the Results section. Add more details in
Method section. Which test did you use for interaction analysis, likelihood ratio or Wald test?
For trend analysis, you used median value of each quartile or treating them as an ordinal variable.
4. Some sensitive analyses are necessary if data are available. (1) among aspirin nonuser group;
(2) among participants with cancer diagnosis of 2 year after enrollment; (3) performed multiple
imputation on covariate missing data.
5. MR did not fully support your results. Your main aim is to assess the associations between
RAR and CRC/GC risk among diverse populations. However, GWAS summary statistics for
RAR and other ancestry groups is not available. You assessed albumin and RDW among
European Ancestry. Several papers were published and identified the inverse associations. What
differences between yours and the previous study? Also, you did not assess GC risk.
Results:
1. How many participants with albumin lying outside the clinically normal range? How many
participants with RDW lying outside the clinically normal range?
Please review this paper.
user
Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 3 Date: 24 Jan 2025
Reviewer's report:
Luo J et al investigated the associations of a novel biomarker, red blood cell distribution width-
to-albumin ratio, with CRC and GC risk. They further used MR techniques to partially validate
their findings from the observation study. This is well- written. However, my concerns are shown
below:
Introduction:
1. NLP and PLR have limited sensitivity and specificity and are predominantly used for
prognostic prediction. Can RAR bridge these gaps? To my knowledge, no studies investigated
the associations of NLP and PLR and CRC/GC risk. We do not know their roles in risk
prediction.
2. Summarize the current literature on the topics of RAR/RDW/albumin and CRC/GC risk.
Method:
1. Included inclusion and exclusion criteria in the Method section. Did you remove the
individuals with cancer diagnosis before the enrollment? I have concerns about the reverse
causation.
2. RAR was calculated already in NHANES dataset? If no, mention how you computed this
biomarker. Also, add unit for albumin.
3. You mentioned trend and interaction analysis in the Results section. Add more details in
Method section. Which test did you use for interaction analysis, likelihood ratio or Wald test?
For trend analysis, you used median value of each quartile or treating them as an ordinal variable.
4. Some sensitive analyses are necessary if data are available. (1) among aspirin nonuser group;
(2) among participants with cancer diagnosis of 2 year after enrollment; (3) performed multiple
imputation on covariate missing data.
5. MR did not fully support your results. Your main aim is to assess the associations between
RAR and CRC/GC risk among diverse populations. However, GWAS summary statistics for
RAR and other ancestry groups is not available. You assessed albumin and RDW among
European Ancestry. Several papers were published and identified the inverse associations. What
differences between yours and the previous study? Also, you did not assess GC risk.
Results:
1. How many participants with albumin lying outside the clinically normal range? How many
participants with RDW lying outside the clinically normal range?
assistant