Lipopolysaccharide (LPS), an endotoxin found on the outer cell wall of gram-negative bacteria, increases inflammatory response signaling, and may play a role in the pathogenesis of several inflammatory-associated diseases, including cancer, diabetes, inflammatory bowel disease, and cardiovascular disease. While LPS is hypothesized to be associated with colorectal carcinogenesis, there are relatively few human studies which have examined this association. Thus, we examined the association between colorectal cancer (CRC) and lipopolysaccharide-binding protein (LBP; a marker of LPS) in 1,760 participants (879 CRC cases and 879 controls) from the Multiethnic Cohort study (MEC). The baseline questionnaire, which was administered between 1993 and 1996, obtained extensive information on demographics, medical and reproductive histories, cigarette smoking, medication use, family history of various cancers, physical activity, and diet using a quantitative food frequency questionnaire. LBP was measured in plasma samples collected between 2001-2005 and incident cancer cases were identified as those occurring after date of plasma collection through 2012 using the Hawaii Tumor Registry (HTR), the Los Angeles County Cancer Surveillance Program (CSP) and the State of California Cancer Registry (CCR), all of which are NCI-funded Surveillance, Epidemiology, and End Results (SEER) registries. Deaths in the cohort were identified by linkage to the state death-certificate files in CA and HI, and with the National Death Index for deaths occurring in other states. Controls were matched to incident cancer cases on age, location, sex, ethnicity, age at phlebotomy, date of specimen collection, time of blood collection, and time since last meal. LBP was grouped into tertiles, with the lowest tertile serving as the reference (mean: 20,797 ng/mL, range: 2,687-27,211 ng/mL). Conditional logistic regression models were used to estimate the multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Covariates were selected a priori and included factors associated with CRC: education, BMI (kg/m2), physical activity, smoking status at time of blood draw, history of intestinal polyps, previous colonoscopy or sigmoidoscopy, diabetes, history of CRC among 1st degree relatives, NSAID use, alcohol consumption, dietary fiber intake, saturated fat intake and hormone replacement therapy use. Compared to individuals whose LBP concentrations were in the lowest tertile, the ORs associated with middle (mean: 32,282 ng/mL, range: 27,211-37,777 ng/mL) and highest (mean: 51,019, range: 37,777-110,390 ng/mL) tertiles were 1.18 (95% CI = 0.85-1.64) and 1.31 (95% CI = 0.92-1.84), respectively, (Ptrend = 0.12). While this study did not find a statistically significant association between LBP and CRC, further studies are needed to understand the interplay between the gut microbiome, LBP, inflammation, and CRC.

This work was supported by grants from the National Institutes of Health (grants P01 CA168530, R25 CA094880, and P01 CA33619).

Citation Format: Jessica Citronberg, Lynne Wilkens, Loic Le Marchand, Unhee Lim, Meredith Hullar, Emily White, Polly Newcomb, Johanna Lampe. Plasma lipopolysaccharide-binding protein and colorectal cancer risk: A nested case-control study in the Multiethnic Cohort (MEC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-373.