Abstract 596: Association between an empirically-derived inflammatory lifestyle score and incident colorectal cancer
Authors: Guinter Mark , Gapstur Susan , Flanders W. Dana , Wang Ying , Rees-Punia Erika , McCullough Marjorie , Alcaraz Kassandra I. , Pollak Michael , Campbell Peter 
Published: August 2019

Abstract
Inflammation is often suggested as major pathway by which lifestyle influences the development of colorectal cancer (CRC). In the present analysis, we empirically derived an inflammatory lifestyle score (ILS) based on associations of nine lifestyle factors with serum levels of high-sensitivity C-reactive protein (hsCRP) and subsequently examined its association with incident CRC in the Cancer Prevention Study-II Nutrition Cohort. Lifestyle factors other than smoking were chosen a priori from the American Cancer Society’s Guidelines on Nutrition and Physical Activity for Cancer Prevention to include body mass index, physical activity, sedentary time, fruit/vegetable intake, variety of fruits/vegetables consumed, red/processed meat intake, ratio of whole to refined grains consumed, alcohol consumption, and smoking status. Reduced rank regression was used to create sex-specific lifestyle scores that correlate the nine lifestyle factors with hsCRP in a testing subset of 2,707 men and women with no history of cancer at the time of blood draw. In a validation subset (n=540), the derived ILS was positively correlated with serum hsCRP levels (r=0.19, p-value&lt;0.001). Model weights from reduced rank regression in the testing subset were used to calculate the ILS among 114,974 men and women of the cohort for whom hsCRP levels were not available. The association between the ILS and incident CRC was examined using Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals adjusted for age, sex, education, non-steroidal anti-inflammatory drug use, multivitamin use, postmenopausal hormone therapy, and diabetes status. Starting at baseline in 1999, during a mean follow-up of 12.6 years, 2,082 incident CRC cases were identified (1,649 colon; 433 rectum). Participants in the third and fourth ILS quartiles had 15% (95% CI: 1%, 31%) and 34% (95% CI: 18%, 53%) higher risk of CRC, respectively, than those in the first ILS quartile. A 1-standard deviation increase in the score was associated with 10% higher risk of CRC (95% CI: 1.05, 1.15). The association between the ILS and CRC did not differ across strata of sex or age (&lt;70, ≥70 years). A Lunn-McNeil competing risk model showed no evidence of a differential association of the ILS on CRC organ subtypes (colon vs. rectal). Results support evidence that a lifestyle indicative of high inflammatory potential is associated with an increased risk of developing CRC. To examine other mechanisms by which lifestyle influences CRC risk, additional analyses will use serum levels of C-peptide and hemoglobin A1c. The biomarkers will be examined individually, together (i.e., glucose homeostasis), and in combination with hsCRP (poor metabolic function) to develop lifestyle scores.
Citation Format: Mark Guinter, Susan Gapstur, W. Dana Flanders, Ying Wang, Erika Rees-Punia, Marjorie McCullough, Kassandra I. Alcaraz, Michael Pollak, Peter Campbell. Association between an empirically-derived inflammatory lifestyle score and incident colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 596.