Macronutrient quality and colorectal cancer outcomes: evidence from the PLCO screening trial

Dazhan Feng; Ling Xiang; Ke Wen; Yi Xiao; Haitao Gu; Linglong Peng; Yuxiang Luo; Yaxu Wang; Dengliang Liu; Zhihang Zhou; Qian Liu

doi:10.3389/fnut.2025.1656275

Macronutrient quality and colorectal cancer outcomes: evidence from the PLCO screening trial

Dazhan Feng
, Ling Xiang
, Ke Wen
, Yi Xiao
, Haitao Gu
, Linglong Peng
, Yuxiang Luo
, Yaxu Wang
, Dengliang Liu
, Zhihang Zhou^*
, Qian Liu^*

^*Corresponding author for this work

Cardiology

The Second Affiliated Hospital of Chongqing Medical University
The Fifth Medical Center of PLA General Hospital
Chongqing Jiulongpo People’s Hospital
Xipeng Town Health Center of Jiulongpo District

Research output: Contribution to journal › Article › Academic › peer-review

3 Downloads (Pure)

Abstract

Background:

No previous study has assessed the relationship between macronutrient quality and colorectal cancer (CRC) incidence and mortality. Thus, to further explore the associations between macronutrient quality and CRC risk, we conducted a large prospective cohort study involving 101,709 people in the United States from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Methods:

Our study population was derived from 154,887 adults aged 55 to 74 years who were recruited from 10 screening centers in the United States. The macronutrient quality index (MQI) was calculated based on dietary history questionnaire (DHQ). Cox regression analysis was utilized to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between MQI and CRC incidence and mortality. We used subgroup analyses to identify potential effect modifiers. Sensitivity analysis was performed to ensure the study findings were robust.

Results:

During the study period, 1,100 colorectal cancer (CRC) diagnoses and 314 CRC-related deaths were recorded. Higher adherence to the MQI was significantly associated with reduced CRC risk, demonstrating a 22% lower incidence (HR Q4 vs. Q1: 0.78; 95% CI: 0.65–0.93; p = 0.006 for trend) and 38% lower mortality (HR Q4 vs. Q1: 0.62; 95% CI: 0.44–0.86; p = 0.001 for trend) in the highest vs. lowest quartiles. These associations were robust across sensitivity analyses. Subsite-specific analyses revealed pronounced protective effects for distal colon cancer incidence (36% reduction; HR: 0.64; 95% CI: 0.43–0.96; p = 0.010 for trend) and mortality (56% reduction; HR: 0.44; 95% CI: 0.19–1.01; p = 0.037 for trend), with significant mortality reductions also observed for proximal colon cancer (34%; HR: 0.66; 95% CI: 0.44–1.00; p = 0.031 for trend).

Conclusion:

Our findings suggest focusing on higher quality of macronutrient consumption may be an effective approach to reduce the risk of CRC in the US population.

Original language	English
Article number	1656275
Journal	Frontiers in Nutrition
Volume	12
DOIs	https://doi.org/10.3389/fnut.2025.1656275
Publication status	Published - 12 Jan 2026

Bibliographical note

Publisher Copyright:
Copyright © 2026 Feng, Xiang, Wen, Xiao, Gu, Peng, Luo, Wang, Liu, Zhou and Liu.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.3389/fnut.2025.1656275Licence: CC BY

Macronutrient quality and colorectal cancer outcomesFinal published version, 1.06 MBLicence: CC BY

Cite this

@article{ca19bcac22684e0b96f382428bec7e47,

title = "Macronutrient quality and colorectal cancer outcomes: evidence from the PLCO screening trial",

abstract = "Background: No previous study has assessed the relationship between macronutrient quality and colorectal cancer (CRC) incidence and mortality. Thus, to further explore the associations between macronutrient quality and CRC risk, we conducted a large prospective cohort study involving 101,709 people in the United States from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: Our study population was derived from 154,887 adults aged 55 to 74 years who were recruited from 10 screening centers in the United States. The macronutrient quality index (MQI) was calculated based on dietary history questionnaire (DHQ). Cox regression analysis was utilized to calculate the hazard ratios (HRs) and 95\% confidence intervals (CIs) of the associations between MQI and CRC incidence and mortality. We used subgroup analyses to identify potential effect modifiers. Sensitivity analysis was performed to ensure the study findings were robust. Results: During the study period, 1,100 colorectal cancer (CRC) diagnoses and 314 CRC-related deaths were recorded. Higher adherence to the MQI was significantly associated with reduced CRC risk, demonstrating a 22\% lower incidence (HR Q4 vs. Q1: 0.78; 95\% CI: 0.65–0.93; p = 0.006 for trend) and 38\% lower mortality (HR Q4 vs. Q1: 0.62; 95\% CI: 0.44–0.86; p = 0.001 for trend) in the highest vs. lowest quartiles. These associations were robust across sensitivity analyses. Subsite-specific analyses revealed pronounced protective effects for distal colon cancer incidence (36\% reduction; HR: 0.64; 95\% CI: 0.43–0.96; p = 0.010 for trend) and mortality (56\% reduction; HR: 0.44; 95\% CI: 0.19–1.01; p = 0.037 for trend), with significant mortality reductions also observed for proximal colon cancer (34\%; HR: 0.66; 95\% CI: 0.44–1.00; p = 0.031 for trend).Conclusion: Our findings suggest focusing on higher quality of macronutrient consumption may be an effective approach to reduce the risk of CRC in the US population.",

author = "Dazhan Feng and Ling Xiang and Ke Wen and Yi Xiao and Haitao Gu and Linglong Peng and Yuxiang Luo and Yaxu Wang and Dengliang Liu and Zhihang Zhou and Qian Liu",

note = "Publisher Copyright: Copyright {\textcopyright} 2026 Feng, Xiang, Wen, Xiao, Gu, Peng, Luo, Wang, Liu, Zhou and Liu.",

year = "2026",

month = jan,

day = "12",

doi = "10.3389/fnut.2025.1656275",

language = "English",

volume = "12",

journal = "Frontiers in Nutrition",

issn = "2296-861X",

publisher = "Frontiers Media SA",

}

TY - JOUR

T1 - Macronutrient quality and colorectal cancer outcomes

T2 - evidence from the PLCO screening trial

AU - Feng, Dazhan

AU - Xiang, Ling

AU - Wen, Ke

AU - Xiao, Yi

AU - Gu, Haitao

AU - Peng, Linglong

AU - Luo, Yuxiang

AU - Wang, Yaxu

AU - Liu, Dengliang

AU - Zhou, Zhihang

AU - Liu, Qian

PY - 2026/1/12

Y1 - 2026/1/12

N2 - Background: No previous study has assessed the relationship between macronutrient quality and colorectal cancer (CRC) incidence and mortality. Thus, to further explore the associations between macronutrient quality and CRC risk, we conducted a large prospective cohort study involving 101,709 people in the United States from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: Our study population was derived from 154,887 adults aged 55 to 74 years who were recruited from 10 screening centers in the United States. The macronutrient quality index (MQI) was calculated based on dietary history questionnaire (DHQ). Cox regression analysis was utilized to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between MQI and CRC incidence and mortality. We used subgroup analyses to identify potential effect modifiers. Sensitivity analysis was performed to ensure the study findings were robust. Results: During the study period, 1,100 colorectal cancer (CRC) diagnoses and 314 CRC-related deaths were recorded. Higher adherence to the MQI was significantly associated with reduced CRC risk, demonstrating a 22% lower incidence (HR Q4 vs. Q1: 0.78; 95% CI: 0.65–0.93; p = 0.006 for trend) and 38% lower mortality (HR Q4 vs. Q1: 0.62; 95% CI: 0.44–0.86; p = 0.001 for trend) in the highest vs. lowest quartiles. These associations were robust across sensitivity analyses. Subsite-specific analyses revealed pronounced protective effects for distal colon cancer incidence (36% reduction; HR: 0.64; 95% CI: 0.43–0.96; p = 0.010 for trend) and mortality (56% reduction; HR: 0.44; 95% CI: 0.19–1.01; p = 0.037 for trend), with significant mortality reductions also observed for proximal colon cancer (34%; HR: 0.66; 95% CI: 0.44–1.00; p = 0.031 for trend).Conclusion: Our findings suggest focusing on higher quality of macronutrient consumption may be an effective approach to reduce the risk of CRC in the US population.

AB - Background: No previous study has assessed the relationship between macronutrient quality and colorectal cancer (CRC) incidence and mortality. Thus, to further explore the associations between macronutrient quality and CRC risk, we conducted a large prospective cohort study involving 101,709 people in the United States from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: Our study population was derived from 154,887 adults aged 55 to 74 years who were recruited from 10 screening centers in the United States. The macronutrient quality index (MQI) was calculated based on dietary history questionnaire (DHQ). Cox regression analysis was utilized to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations between MQI and CRC incidence and mortality. We used subgroup analyses to identify potential effect modifiers. Sensitivity analysis was performed to ensure the study findings were robust. Results: During the study period, 1,100 colorectal cancer (CRC) diagnoses and 314 CRC-related deaths were recorded. Higher adherence to the MQI was significantly associated with reduced CRC risk, demonstrating a 22% lower incidence (HR Q4 vs. Q1: 0.78; 95% CI: 0.65–0.93; p = 0.006 for trend) and 38% lower mortality (HR Q4 vs. Q1: 0.62; 95% CI: 0.44–0.86; p = 0.001 for trend) in the highest vs. lowest quartiles. These associations were robust across sensitivity analyses. Subsite-specific analyses revealed pronounced protective effects for distal colon cancer incidence (36% reduction; HR: 0.64; 95% CI: 0.43–0.96; p = 0.010 for trend) and mortality (56% reduction; HR: 0.44; 95% CI: 0.19–1.01; p = 0.037 for trend), with significant mortality reductions also observed for proximal colon cancer (34%; HR: 0.66; 95% CI: 0.44–1.00; p = 0.031 for trend).Conclusion: Our findings suggest focusing on higher quality of macronutrient consumption may be an effective approach to reduce the risk of CRC in the US population.

UR - https://www.scopus.com/pages/publications/105028421222

U2 - 10.3389/fnut.2025.1656275

DO - 10.3389/fnut.2025.1656275

M3 - Article

C2 - 41601909

AN - SCOPUS:105028421222

SN - 2296-861X

VL - 12

JO - Frontiers in Nutrition

JF - Frontiers in Nutrition

M1 - 1656275

ER -

Macronutrient quality and colorectal cancer outcomes: evidence from the PLCO screening trial

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this