Associations of Circulating Inflammatory Biomarkers with Risk Factors for Colorectal Cancer in Colorectal Adenoma Patients

Hopkins, Myfanwy; Flanders, W. Dana; Bostick, Roberd M.

doi:10.4137/bmi.s10092

Cited by 20 publications

(12 citation statements)

References 24 publications

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“…Concentrations of inflammation markers were comparable to those in the pilot trial, which had a much shorter gap between sample collection and laboratory measurement (21). Most importantly, associations of these biomarkers at baseline with sex, body measurements, and an oxidative balance score were consistent with previous findings from our group (42,45,46) and other groups (e.g., refs. [47][48][49], supporting the validity of our biomarker measurements.…”

Section: Discussionsupporting

confidence: 87%

Effects of Calcium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Colorectal Adenoma Patients: A Randomized Controlled Trial

Yang

Gross

Fedirko

et al. 2015

Cancer Prevention Research

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Inflammation and oxidative stress play important roles in colorectal carcinogenesis. There is strong evidence that calcium reduces risk for colorectal neoplasms, possibly through its ability to bind bile acids and prevent their colonic toxicity (which occurs via an oxidative mechanism and results in an inflammatory response). In a previously reported pilot, randomized, controlled trial among sporadic colorectal adenoma patients we found that those on 2.0 g/day of calcium, relative to those on placebo, had an estimated drop in a combined cytokine z-score of 48% (P ¼ 0.18) over 6 months. To follow-up these promising preliminary findings, we tested the efficacy of two doses of supplemental calcium (1.0 or 2.0 g/day) relative to placebo on modulating circulating biomarkers of inflammation [C-reactive protein (CRP) and 10 cytokines] and oxidative stress (F 2 -isoprostanes) over a 4-month treatment period among 193 patients with previous sporadic, colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial. The inflammation markers were measured in plasma using electrochemiluminescence detection-based immunoassays, and F 2 -isoprostanes were measured in plasma using gas chromatography-mass spectrometry. Over a 4-month treatment period, we found no appreciable effects of calcium on CRP, cytokines, or F 2 -isoprostanes (P > 0.4), overall or within strata of several major risk factors for colorectal carcinogenesis, such as body mass index and regular use of nonsteroidal anti-inflammatory drugs. Overall, our results provide no evidence that calcium supplementation favorably modulates concentrations of circulating biomarkers of inflammation or oxidative stress over 4 months among patients with a previous colorectal adenoma. Cancer Prev Res; 8(11); 1069-75.Ó2015 AACR.

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Section: Discussionsupporting

confidence: 87%

Effects of Calcium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Colorectal Adenoma Patients: A Randomized Controlled Trial

Yang

Gross

Fedirko

et al. 2015

Cancer Prevention Research

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“…The choice of a composite inflammatory score is somewhat arbitrary, and there are multiple methods of computing a composite inflammatory score [48]. The method that we presented in this paper of examining those with two or more inflammatory markers in the top quartile has also been published previously and represents a more specific indicator of systemic inflammation than a high level of just one inflammatory marker [4, 49–51].…”

Section: Discussionmentioning

confidence: 99%

Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men

et al. 2016

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Summary Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors. Introduction Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D. Methods We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study. Results IL-6 was lower in men with higher 25OHD (−0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) −0.07 to −0.38 μg/mL) and with higher 1,25(OH)2D (−0.20 μg/mL, 95 % CI −0.0004 to −0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1, 25(OH)2D). Conclusions Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1, 25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

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“…Most studies of colorectal polyps focused on select markers of inflammation, most commonly IL-6, TNF-α and c-reactive protein (CRP) (Hopkins et al, 2012; Il'yasova et al, 2005; Kim et al, 2008; Wild et al, 2010). These studies found IL-6, TNF-α, and CRP as well as non-cytokine markers, such as carcinoembryonic antigen and ferritin, are positively associated with the presence of colorectal adenomas as well as with general cancer incidence.…”

Section: Discussionmentioning

confidence: 99%

Association of serum cytokines with colorectal polyp number and type in adult males

Comstock

Hortos

et al. 2016

European Journal of Cancer Prevention

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Chronic inflammation contributes to colorectal carcinogenesis. To determine if serum cytokines are associated with colon polyps, 126 asymptomatic men (48–65yr) were recruited at colonoscopy. Serum cytokine concentrations were measured. Odds ratios were determined using polytomous logistic regression for polyp number and type. Males with serum monocyte chemotactic protein-3 (MCP-3) or soluble interleukin-4 receptor (sIL-4R) concentrations in the highest tertile were 0.2 times less likely to have ≥3 polyps relative to no polyps. For each increase in serum MCP-3 or sIL-4R tertile a man was about 0.4 times less likely to have ≥3 polyps than no polyps. Males with serum concentrations of interferon-α2 (IFN-α2) or interleukin (IL)-7 in the highest tertile were 3 times more likely to have an adenoma relative to no polyps. Those with serum IL-8 concentrations in the highest tertile were 4 times more likely to have an adenoma relative to no polyps. For each increase in serum IFN-α2, IL-7 or IL-8 tertile an individual was 1.8 times more likely to have an adenoma than no polyp. Serum concentrations of MCP-3, sIL-4R, IFN-α2, IL-7 and IL-8 may indicate which men are more likely to have colorectal polyps.

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Associations of Circulating Inflammatory Biomarkers with Risk Factors for Colorectal Cancer in Colorectal Adenoma Patients

Cited by 20 publications

References 24 publications

Effects of Calcium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Colorectal Adenoma Patients: A Randomized Controlled Trial

Effects of Calcium Supplementation on Biomarkers of Inflammation and Oxidative Stress in Colorectal Adenoma Patients: A Randomized Controlled Trial

Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men

Association of serum cytokines with colorectal polyp number and type in adult males

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