Plasma lipopolysaccharide-binding protein and colorectal cancer risk: a nested case-control study in the Multiethnic Cohort.

BACKGROUND: 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 adverse outcomes, including inflammatory bowel diseases, cardiovascular disease, and cancer. While LPS is hypothesized to be associated with colorectal carcinogenesis, there are relatively few human studies which have examined this association. METHODS: We examined the association between colorectal cancer (CRC) and plasma lipopolysaccharide-binding protein (LBP), a marker of LPS, in 1,638 participants (819 CRC cases and 819 controls) matched on multiple factors, including age, sex, and race/ethnicity, from the Multiethnic Cohort study. Conditional logistic regression models were used to estimate the multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Compared to individuals whose LBP concentrations were in the lowest quartile, the ORs associated with second, third, and fourth quartiles were 1.23 (95% CI 0.91-1.67), 1.36 (95% CI 1.01-1.83), and 1.01 (95% CI 0.73-1.39), respectively, (p trend = 0.66). No differences were observed by BMI, fiber intake, saturated fat intake, cancer site, or cancer stage. CONCLUSIONS: This study did not find an overall statistically significant association between LBP (as a marker of LPS exposure) and CRC. Further prospective studies with multiple LBP measurements are needed to validate current findings.

Reliability of plasma lipopolysaccharide-binding protein (LBP) from repeated measures in healthy adults.

Plasma lipopolysaccharide-binding protein (LBP), a measure of internal exposure to bacterial lipopolysaccharide, has been associated with several chronic conditions and may be a marker of chronic inflammation; however, no studies have examined the reliability of this biomarker in a healthy population. We examined the temporal reliability of LBP measured in archived samples from participants in two studies. In Study one, 60 healthy participants had blood drawn at two time points: baseline and follow-up (either three, six, or nine months). In Study two, 24 individuals had blood drawn three to four times over a seven-month period. We measured LBP in archived plasma by ELISA. Test-retest reliability was estimated by calculating the intraclass correlation coefficient (ICC). Plasma LBP concentrations showed moderate reliability in Study one (ICC 0.60, 95 % CI 0.43-0.75) and Study two (ICC 0.46, 95 % CI 0.26-0.69). Restricting the follow-up period improved reliability. In Study one, the reliability of LBP over a three-month period was 0.68 (95 % CI: 0.41-0.87). In Study two, the ICC of samples taken ≤seven days apart was 0.61 (95 % CI 0.29-0.86). Plasma LBP concentrations demonstrated moderate test-retest reliability in healthy individuals with reliability improving over a shorter follow-up period.

Laxative type in relation to colorectal cancer risk.

PURPOSE: Existing studies on laxatives, used by roughly 40% of the U.S. population experiencing constipation and colorectal cancer (CRC) have yielded inconsistent results, which may be due to a failure to account for differential risks by major laxative types: bulk (fiber-based), and nonbulk (or nonfiber-based). METHODS: We examined the association of nonfiber-based laxative use and fiber-based laxative use with the risk of CRC in a subset of the multisite, International Colon Cancer Family Registry cohort comprising 4930 primary invasive CRC cases and 4025 controls selected from the general population. Epidemiologic risk factor questionnaires were administered to all participants at recruitment, and exposures were ascertained approximately 1 year before diagnosis for cases and at a comparable period for controls. We ascertained known and suspected CRC risk factors, including regular laxative use, which was defined as laxative intake at least twice a week for more than a month. Multivariable logistic regression models were used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Individuals who reported using nonfiber-based laxatives regularly were at a significantly increased risk for CRC compared with those who reported no laxative use (OR = 2.17, 95% CI = 1.47-3.19). No statistically significant associations were observed between fiber-based laxative use and CRC (OR = 0.99, 95% CI = 0.80-1.22). CONCLUSIONS: Compared with nonusers, the risk of CRC increased with nonfiber-based laxative use, whereas CRC risk was not significantly associated with fiber-based laxative use.

Association of gut microbial communities with plasma lipopolysaccharide-binding protein (LBP) in premenopausal women.

The mechanisms by which obesity increases cancer risk are unclear, but some lines of evidence suggest that gut microbial communities (GMC) may contribute to chronic inflammation in obese individuals through raised systemic levels of lipopolysaccharides (LPS). We evaluated associations of the GMC in stool with plasma LPS-binding protein (LBP, a measure of LPS) and C-reactive protein (CRP) concentrations in 110 premenopausal women in the United States. Diet was assessed using 3-day food records and GMCs were evaluated using pyrosequencing of the 16S rRNA gene. OTUs were identified at 97% sequence similarity. Taxonomic classification and functional genes were imputed from 16S rRNA genes, and alpha and beta diversity were assessed using the Shannon index and MRPP, respectively. Multivariable linear regression analysis was used to assess the relation between LBP, specific bacterial genera identified with indicator species analysis, and CRP. Dietary fat intake, particularly saturated fat, and CRP were positively associated with increased LBP. GMC beta diversity, but not alpha diversity, was statistically significantly different between groups using unweighted Unifrac. Several taxa, particularly those in the Clostridia class, were more prevalent in women with low LBP, while Bacteroides were more prevalent in those with high LBP. Genes associated with gram-negative cell wall material synthesis were also associated with LBP and CRP. In contrast, Phascolarctobacterium was associated with lower concentrations of LBP and CRP. We found distinct differences between tertiles of LBP regarding the diversity and composition of the microbiome, as well as differences in functional genes that potentially activate LBP.