Development and validation of Comprehensive Inflammatory Lifestyle Score and association with colorectal cancer risk.

Background: A comprehensive inflammatory lifestyle score (CILS) incorporating both dietary and non-dietary factors is lacking. This study aimed to develop and validate CILS and assess its association with colorectal cancer (CRC) risk.

Methods: Eligible participants in the UK Biobank with data on baseline lifestyle factors and serum biomarkers measured 2 years later were randomly divided into training (N=4108) and validation (N=1760) datasets based on sex, age and race. Reduced rank regression followed by stepwise linear regression identified significant lifestyle factors (i.e., components of CILS) correlated with high-sensitivity C-reactive protein (hsCRP) and white blood count (WBC) from 24 a priori-selected inflammation-related factors. CILS was validated using multiple linear regression. Cox models were applied to examine the associations of CILS with incidence and mortality risk of CRC and subtypes in the remaining 182,814 participants.

Results: CILS comprised three anti-inflammatory factors [low body weight (BMI<18.5), higher intake of fish, and apples/berries] and five pro-inflammatory factors [obesity/overweight, prolonged sedentary time (the highest tertile in the population), current smoking, whole-fat dairy, and processed meat] with higher CILS indicating a more proinflammatory lifestyle. Validation analyses demonstrated a 22.2% and 2.8% increase in hsCRP and WBC for each SD increment in CILS respectively. Higher CILS was linked to increased CRC incidence (HRper- SD-increase=1.12, 95%CI=1.08-1.16) and mortality (HRper- SD-increase=1.18, 95%CI=1.08-1.28), and increased risk of all CRC subtypes except incident rectal cancer.

Conclusions: The validated hypothesis-driven and empirically-derived CILS was positively associated with CRC risk in the UK Biobank.

Impact: CILS may offer promising applications in cancer prevention.