Title: The additive interaction of healthy lifestyles and genetic susceptibility on colorectal
cancer risk in prediabetes: a large population-based prospective cohort study
Version: 3 Date: 28 Oct 2024
Reviewer's report:
1. More details on the follow-up in the cohort, person-time, and censoring in the analyses need
to be provided.
2. Competing risk analyses may be beneficial as sensitivity analyses to correct for presence of
competing events.
3. Although the hypothesis of this study is examining additive interactions, the manuscript could
benefit from examining in parallel  in the same cohort multiplicative interaction (model with
interaction term) in non-stratified models. In the methods, it is mentioned that multiplicative
interaction is being in fact assessed, but no mention to it is directly provided in the rest of the
manuscript (results, discussion). Synergistic effects in results are mentioned in the title section
but the term needs to be also clarified or consistently referred to throughout the manuscript.
4. Proportional hazards assumptions need to be tested prior to analyses.
5. Is the HLS score validated ? Citations may be needed. Also is the HLS with 5 behaviors
commonly used in other cohorts as opposed to including more behaviors/indicators like sleep
patterns, sedentarism, etc?
6. Fig 3a label “male” is missing
7. More literature examining these interactions on CRC risk in prediabetic population needs to
be provided. Otherwise, if this is the first study examining this hypothesis it needs to be stated.
It is unclear in the text as it is currently.
Title: The additive interaction of healthy lifestyles and genetic susceptibility on colorectal
cancer risk in prediabetes: a large population-based prospective cohort study
Version: 3 Date: 28 Oct 2024
Reviewer's report:
1. More details on the follow-up in the cohort, person-time, and censoring in the analyses need
to be provided.
2. Competing risk analyses may be beneficial as sensitivity analyses to correct for presence of
competing events.
3. Although the hypothesis of this study is examining additive interactions, the manuscript could
benefit from examining in parallel  in the same cohort multiplicative interaction (model with
interaction term) in non-stratified models. In the methods, it is mentioned that multiplicative
interaction is being in fact assessed, but no mention to it is directly provided in the rest of the
manuscript (results, discussion). Synergistic effects in results are mentioned in the title section
but the term needs to be also clarified or consistently referred to throughout the manuscript.
4. Proportional hazards assumptions need to be tested prior to analyses.
5. Is the HLS score validated ? Citations may be needed. Also is the HLS with 5 behaviors
commonly used in other cohorts as opposed to including more behaviors/indicators like sleep
patterns, sedentarism, etc?
6. Fig 3a label “male” is missing
7. More literature examining these interactions on CRC risk in prediabetic population needs to
be provided. Otherwise, if this is the first study examining this hypothesis it needs to be stated.
It is unclear in the text as it is currently.
Please review this paper.
user
Title: The additive interaction of healthy lifestyles and genetic susceptibility on colorectal
cancer risk in prediabetes: a large population-based prospective cohort study
Version: 3 Date: 28 Oct 2024
Reviewer's report:
1. More details on the follow-up in the cohort, person-time, and censoring in the analyses need
to be provided.
2. Competing risk analyses may be beneficial as sensitivity analyses to correct for presence of
competing events.
3. Although the hypothesis of this study is examining additive interactions, the manuscript could
benefit from examining in parallel  in the same cohort multiplicative interaction (model with
interaction term) in non-stratified models. In the methods, it is mentioned that multiplicative
interaction is being in fact assessed, but no mention to it is directly provided in the rest of the
manuscript (results, discussion). Synergistic effects in results are mentioned in the title section
but the term needs to be also clarified or consistently referred to throughout the manuscript.
4. Proportional hazards assumptions need to be tested prior to analyses.
5. Is the HLS score validated ? Citations may be needed. Also is the HLS with 5 behaviors
commonly used in other cohorts as opposed to including more behaviors/indicators like sleep
patterns, sedentarism, etc?
6. Fig 3a label “male” is missing
7. More literature examining these interactions on CRC risk in prediabetic population needs to
be provided. Otherwise, if this is the first study examining this hypothesis it needs to be stated.
It is unclear in the text as it is currently.
assistant