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.

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.

Relation of Vitamin E and Selenium Exposure to Prostate Cancer Risk by Smoking Status: A Review and Meta-Analysis.

BACKGROUND: Epidemiological studies of selenium and vitamin E, two antioxidants hypothesized to reduce prostate cancer risk, have shown no discernible benefit. It has been proposed, however, that tobacco smoking may modify the effect of these nutrients. MATERIALS AND METHODS: We performed a meta-analysis of studies evaluating the relation of vitamin E and selenium exposure to prostate cancer risk in never smokers vs. ever smokers and, when feasible, former and current smokers. Overall and stratum-specific meta-risk ratios (meta-RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: A total of 21 studies have met the inclusion criteria. Meta-RR (95% CI) estimates of prostate cancer associated with vitamin E use were 1.03 (0.95-1.11) in never smokers and 0.98 (0.90-1.07) in ever-smokers. For selenium, meta-RRs were 1.09 (0.78-1.52 and 0.76 (0.60-0.96) for never and ever-smokers, respectively; however, results for current smokers were weaker than those for former smokers. Sub-analyses according to different exposure assessment methods and outcome definitions produced similar results across strata. CONCLUSION: The association between vitamin E and prostate cancer is not modified by smoking. Selenium exposure is associated with lower prostate cancer risk among ever-smokers; however, the lack of an association for current smokers indicates that this finding needs to be interpreted with caution.

A prospective study of the effect of bowel movement frequency, constipation, and laxative use on colorectal cancer risk.

OBJECTIVES: Constipation and laxative use have been hypothesized to increase colorectal cancer (CRC) risk, but existing epidemiologic studies have been inconclusive. To address this issue, the authors prospectively examined the association between CRC incidence and constipation, non-fiber laxative use, and fiber laxative use among 75,214 participants of the VITamins And Lifestyle study. METHODS: Information on bowel movement frequency as well as average 10-year non-fiber laxative use, fiber laxative use, and constipation was ascertained by means of a questionnaire. Patients were followed from the time of receipt of the baseline questionnaire (2000-2002) until 2008 for CRC incidence, over which time 558 incident CRC cases occurred. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). RESULTS: Compared with individuals who used non-fiber laxatives less than once per year, the HRs associated with low (1-4 times per year) and high (≥5 times per year) use were 1.49 (95% CI: 1.04-2.14) and 1.43 (95% CI: 0.82-2.28), respectively (Ptrend=0.05). HRs for CRC were statistically significantly decreased and lowest in individuals who reported using fiber laxatives often (4+ days per week for 4+ years) vs. those who reported no use (HR=0.44; 95% CI: 0.21-0.95), although the trend was not significant (Ptrend=0.19). No statistically significant associations between bowel movement frequency or constipation and CRC risk were observed. CONCLUSIONS: Findings from this study suggest that risk for CRC increases with non-fiber laxative use and decreases with fiber laxative use. However, further observational and experimental studies are needed to clarify these relationships before drawing conclusions about the preferred treatment of constipation.

Oxidative balance score and risk for incident prostate cancer in a prospective U.S. cohort study.

PURPOSE: Oxidative stress is defined as an imbalance between pro-oxidants and antioxidants. Previous research found that a single comprehensive oxidative balance score (OBS) that includes individual pro- and anti-oxidant exposures may be associated with various conditions (including prostate cancer) in the absence of associations with the individual factors. We investigated an OBS-incident prostate cancer association among 43,325 men in the Cancer Prevention Study II Nutrition Cohort. METHODS: From 1999-2007, 3386 incident cases were identified. Twenty different components, used in two ways (unweighted or weighted based on literature reviews), were incorporated into the OBS, and the resulting scores were then expressed as three types of variables (continuous, quartiles, or six equal intervals). Multivariable-adjusted rate ratios were calculated using Cox proportional hazards models. RESULTS: We hypothesized that the OBS would be inversely associated with prostate cancer risk; however, the rate ratios (95% confidence intervals) comparing the highest with the lowest OBS categories ranged from 1.17 (1.04-1.32) to 1.39 (0.90-2.15) for all cases, 1.14 (0.87-1.50) to 1.59 (0.57-4.40) for aggressive disease (American Joint Committee on Cancer stage III/IV or Gleason score 8-10), and 0.91 (0.62-1.35) to 1.02 (1.02-1.04) for nonaggressive disease. CONCLUSIONS: Our findings are not consistent with the hypothesis that oxidative balance-related exposures collectively affect risk for prostate cancer.

Effects of ginger supplementation on cell-cycle biomarkers in the normal-appearing colonic mucosa of patients at increased risk for colorectal cancer: results from a pilot, randomized, and controlled trial.

To estimate the effects of ginger on apoptosis, proliferation, and differentiation in the normal-appearing colonic mucosa, we randomized 20 people at increased risk for colorectal cancer to 2.0 g of ginger or placebo daily for 28 days in a pilot trial. Overall expression and distributions of Bax, Bcl-2, p21, hTERT, and MIB-1 (Ki-67) in colorectal crypts in rectal mucosa biopsies were measured using automated immunohistochemistry and quantitative image analysis. Relative to placebo, Bax expression in the ginger group decreased 15.6% (P = 0.78) in the whole crypts, 6.6% (P = 0.95) in the upper 40% (differentiation zone) of crypts, and 21.7% (P = 0.67) in the lower 60% (proliferative zone) of crypts; however, there was a 19% increase (P = 0.14) in Bax expression in the upper 40% relative to the whole crypt. While p21 and Bcl-2 expression remained relatively unchanged, hTERT expression in the whole crypts decreased by 41.2% (P = 0.05); the estimated treatment effect on hTERT expression was larger in the upper 40% of crypts (-47.9%; P = 0.04). In the ginger group, MIB-1 expression decreased in the whole crypts, upper 40% of crypts, and lower 60% of crypts by 16.9% (P = 0.39), 46.8% (P = 0.39), and 15.3% (P = 0.41), respectively. These pilot study results suggest that ginger may reduce proliferation in the normal-appearing colorectal epithelium and increase apoptosis and differentiation relative to proliferation--especially in the differentiation zone of the crypts and support a larger study to further investigate these results.