EP770 - Mediating Roles of Prediabetes and Inflammation in the Relationship Between Body Mass Index and Colorectal Cancer Risk

Monday, May 12, 2025

1:47 PM – 1:52 PM PT

ePoster Presenter(s)

Hsin-Yin Hsu, MD, MS (she/her/hers)

Attending physician
Department of Family Medicine, Taipei MacKay Memorial Hospital
Taipei, Taipei, Taiwan (Republic of China)

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

Author(s)

Yih Jong Chern

attending physician
chang gung memorial hospital
Guishan District, Taoyuan, Taiwan (Republic of China)

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
MT

Ming-Chen Tsai, MD,MS

attending physician
Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)

Disclosure information not submitted.
HF

Hsien-Yu Fan, PhD

Assistant professor
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)

Disclosure information not submitted.
PL

Po-Jui Lai, n/a

Clerk
School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)

Disclosure information not submitted.
CL

Chih-Jun Lai, MD

Attending physician
Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)

Disclosure information not submitted.

Senior Author(s)

KC

Kuo-Liong Chien, MD,PhD

Professor
Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

All of the relevant financial relationships listed below have been mitigated.

Hsin-Yin Hsu, MD, MS: This individual has no financial relationships with ineligible companies.

Yih Jong Chern: This individual has no financial relationships with ineligible companies.

Kuo-Liong Chien, MD,PhD: This individual has no financial relationships with ineligible companies.

Image or Table (Do Not add text here):

Purpose/Background: Previous studies have demonstrated that elevated body mass index (BMI) is associated with an increased risk of colorectal cancer (CRC). However, the specific biological pathways mediating this relationship are not fully understood. This study investigates the potential mediating roles of metabolic and inflammatory markers in the BMI-CRC risk relationship, focusing on status of glucose hemostasis and inflammation markers.

Methods/Interventions: We utilized data from the UK Biobank to analyze the association between BMI and CRC risk. Key inflammation markers, including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were considered, along with metabolic markers such as prediabetes status (defined by hemoglobin A1c ≥ 5.7%) and insulin-like growth factor. A four-way decomposition mediation analysis was employed to separate the total effect into the controlled direct effect, the interaction between BMI and mediators, the combined interaction and mediation effect, and the pure indirect effect.

Results/Outcomes: This study included 321,820 participants from the UK Biobank, with a median follow-up of 14.2 years. During this period, 2,858 cases of CRC were recorded. BMI was significantly associated with increased CRC risk, with each unit increase in BMI corresponding to a 2.8% increase in risk (adjusted hazard ratio = 1.028, p < 0.0001). Prediabetes was identified as a significant mediator, accounting for 15.1% (p = 0.003) of the total effect. This mediation was largely driven by the pure indirect effect (13.0%, p = 0.007), with a smaller contribution from the interaction effect (2.1%, p = 0.026). CRP also mediated the BMI-CRC relationship, contributing 13.6% (p = 0.026) of the total effect, again primarily through the pure indirect effect.

Conclusion/Discussion: Our findings highlight the modest yet significant roles of prediabetes status and CRP in mediating the association between BMI and CRC risk, contributing 15.1% and 13.6% of the total effect, respectively. These results reinforce the importance of metabolic dysregulation and inflammation in the relationship between obesity and CRC. Interventions aimed at maintaining glucose homeostasis and reducing inflammation, particularly CRP levels, may help mitigate CRC risk in individuals with higher BMI.