Circulating inflammation markers and colorectal adenoma risk.
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ABSTRACT:
SUBMITTER: Huang WY
PROVIDER: S-EPMC6612053 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Circulating inflammation markers and colorectal adenoma risk.
Huang Wen-Yi WY Berndt Sonja I SI Shiels Meredith S MS Katki Hormuzd A HA Chaturvedi Anil K AK Wentzensen Nicolas N Trabert Britton B Kemp Troy J TJ Pinto Ligia A LA Hildesheim Allan A Rothman Nathaniel N Purdue Mark P MP
Carcinogenesis 20190701 6
Inflammation is a driver of colorectal neoplasia; however, what particular inflammatory processes play a role in early carcinogenesis are unclear. We compared serum levels of 78 inflammation markers between 171 pathologically confirmed colorectal adenoma cases (including 48 incident cases) and 344 controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used weighted multivariable logistic regression to compute odds ratio (OR) and 95% confidence interval (CI). We fou ...[more]
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| S-EPMC6736954 | biostudies-literature
Project description:An oxidative balance score (OBS) that combines pro- and antioxidant exposures was previously reported to be associated with incident sporadic colorectal adenoma. We extend the previous analyses by assessing associations of the OBS and colorectal adenoma with circulating biomarkers of oxidative stress [F2-isoprostanes (FIP) and fluorescent oxidation products (FOP)], and inflammation [C-reactive protein (CRP)].Using pooled data from two previously conducted colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 365), the OBS was constructed and divided into three approximately equal intervals, with the lowest interval used as the reference. Biomarker levels were dichotomized as "high" versus "low" based on the median values among controls. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).For the OBS-adenoma association, the ORs (95% CIs) for the middle and highest (relative to the lowest) score intervals were 0.81 (0.46-1.43) and 0.39 (0.17-0.89), respectively. The corresponding OBS category-specific ORs (95% CIs) were 0.50 (0.25-1.01) and 0.25 (0.10-0.65) for FIP, 2.01 (1.13-3.75) and 3.48 (1.51-8.02) for FOP, and 0.57 (0.31-1.04) and 0.21 (0.09-0.49) for CRP. The ORs (95% CIs) reflecting associations of adenoma with high levels of FIP, FOP, and CRP were 1.89 (1.08-3.30), 1.82 (1.11-2.99), and 1.45 (0.88-2.40), respectively.As hypothesized, the OBS was inversely associated with colorectal adenoma and circulating FIP and CRP levels. The reason for the unexpected direct OBS-FOP association is unknown.These data support the use of combined measures of pro- and antioxidant exposures in studies of colorectal neoplasia.
| S-EPMC3959731 | biostudies-literature
Project description:Evidence remains inconclusive about the association of systemic inflammatory markers with colorectal neoplasia. We investigated whether circulating inflammatory markers were associated with risk of advanced colorectal adenoma. We measured plasma macrophage inhibitory cytokine-1 (MIC-1), C-reactive protein (CRP), interleukin-6 (IL6), and soluble TNF receptor 2 (sTNFR-2) in blood samples drawn from 32,826 women in 1989 to 1990 in the Nurses' Health Study. Through 2008, we documented 757 cases of advanced colorectal adenomas (?1 cm or any size with advanced histology); each case was matched by age and time of blood draw with one control randomly selected from participants who underwent lower endoscopy and did not have neoplasia. Plasma MIC-1 was associated with higher risk of advanced adenoma (Ptrend = 0.04), with an OR of 1.55 (95% confidence interval, 1.03-2.32) comparing extreme quintiles of MIC-1 after adjusting for colorectal cancer-risk factors and other inflammatory markers. Among cases, MIC-1 level was positively associated with the number of adenomas (P < 0.001) and gradually increased from adenomas located in the rectum, distal colon, and up to the proximal colon. There was a strong positive association between MIC-1 and risk of adenomas with multiplicity, ?1 cm size and location in the proximal colon (all Ptrend < 0.05). CRP, IL6, or sTNFR-2 was not associated with adenoma risk. In conclusion, plasma MIC-1 was associated with higher risk of colorectal adenoma, especially multiple, large, and proximal adenomas. Our results provide further support for a role for MIC-1 in carcinogenesis and the potential for MIC-1 as an adjunctive biomarker for detection of advanced colorectal adenoma.
| S-EPMC4706809 | biostudies-literature
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| S-EPMC5964716 | biostudies-other
Project description:We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4). Conditional logistic regression was used to calculate odds ratios (OR) for adenomas (overall and by size, histology, location, number). Polymorphisms in the inflammatory-related genes CRP, ADIPOQ, IL6, and TLR4 were observed to be associated with adenoma risk. At rs1205 in CRP, T (minor allele) carriers had a higher risk (OR 1.67, 95%CI 1.07-2.60; reference: CC) of adenomas overall and adenomas with aggressive characteristics. At rs1201299 in ADIPOQ, the AC genotype had a higher risk (OR 1.58, 95%CI 1.00-2.49) of adenomas, while the minor AA genotype had a borderline inverse association (OR 0.44, 95%CI 0.18-1.08; reference: CC). At rs1800797 in IL6, the AA genotype had a borderline inverse association (OR 0.53, 95%CI 0.27-1.05; reference: GG). Three TLR4 tagSNPs (rs10116253, rs1927911, rs7873784) were associated with adenomas among obese participants. None of these SNPs were associated with colorectal cancer in our prior study in CLUE II, possibly suggesting a different genetic etiology for early colorectal neoplasia.
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Project description:BACKGROUND:Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer. METHODS:We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1?, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNF?, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. RESULTS:We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98-2.52, P = 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95-2.38, P = 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03-2.58, P = 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02-2.51, P = 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90-2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors. CONCLUSIONS AND IMPACT:This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.
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Project description:BackgroundDespite growing recognition of an etiologic role for inflammation in lung carcinogenesis, few prospective epidemiologic studies have comprehensively investigated the association of circulating inflammation markers with lung cancer.MethodsWe conducted a nested case-control study (n = 526 lung cancer patients and n = 592 control subjects) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Control subjects were matched to lung cancer case patients on age, sex, follow-up time (median = 2.9 years), randomization year, and smoking (pack-years and time since quitting). Serum levels of 77 inflammation markers were measured using a Luminex bead-based assay. Conditional logistic regression and weighted Cox models were used to estimate odds ratios (ORs) and cumulative risks, respectively.ResultsOf 68 evaluable markers, 11 were statistically significantly associated with lung cancer risk (P trend across marker categories < .05), including acute-phase proteins (C-reactive protein [CRP], serum amyloid A [SAA]), proinflammatory cytokines (soluble tumor necrosis factor receptor 2 [sTNFRII]), anti-inflammatory cytokines (interleukin 1 receptor antagonist [IL-1RA]), lymphoid differentiation cytokines (interleukin 7 [IL-7]), growth factors (transforming growth factor alpha [TGF-A]), and chemokines (epithelial neutrophil-activating peptide 78 [ENA 78/CXCL5], monokine induced by gamma interferon [MIG/CXCL9], B cell-attracting chemokine 1 [BCA-1/CXCL13], thymus activation regulated chemokine [TARC/CCL17], macrophage-derived chemokine [MDC/CCL22]). Elevated marker levels were associated with increased lung cancer risk, with odds ratios comparing the highest vs the lowest group ranging from 1.47 (IL-7) to 2.27 (CRP). For IL-1RA, elevated levels were associated with decreased lung cancer risk (OR = 0.71; 95% confidence interval = 0.51 to 1.00). Associations did not differ by smoking, lung cancer histology, or latency. A cross-validated inflammation score using four independent markers (CRP, BCA-1/CXCL13, MDC/CCL22, and IL-1RA) provided good separation in 10-year lung cancer cumulative risks among former smokers (quartile [Q] 1 = 1.1% vs Q4 = 3.1%) and current smokers (Q1 = 2.3% vs Q4 = 7.9%) even after adjustment for smoking.ConclusionsSome circulating inflammation marker levels are associated with prospective lung cancer risk.
| S-EPMC3888091 | biostudies-literature
Project description:Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score. Of 64 markers, 22 were associated with endometrial cancer risk at p?<?0.05 and 17 of 22 markers remained associated after multiple testing corrections. After adjusting for BMI and estradiol, SERPINE1 [quartile(Q)4 vs. Q1 odds ratio (OR) (95% confidence interval (CI)), p trend?=?2.43 (0.94-6.29), 0.03] and VEGFA [2.56 (1.52-4.30), 0.0002] were positively associated with endometrial cancer risk, while CCL3 [0.46 (0.27-0.77), 0.01], IL13 [0.55 (0.33-0.93), 0.01], IL21 [0.52 (0.31-0.87), 0.01], IL1B [0.51 (0.30-0.86), 0.01] and IL23 [0.60 (0.35-1.03), 0.02] were inversely associated with risk. We observed large differences in ORs across BMI-inflammation score categories. Endometrial cancer risk was most pronounced among obese women with the highest inflammation score tertile (T) [10.25 (3.56-29.55) vs. normal BMI/T1]. Several inflammation markers were prospectively associated with endometrial cancer, including adipokines, pro- and anti-inflammatory cytokines, angiogenic factors and acute phase proteins. Inverse associations with anti-inflammatory markers (IL13, IL21), other inflammation markers/mediators (CCL3, IL1B, IL23), and a robust positive association between VEGFA and endometrial cancer risk were independent of BMI and estradiol, suggesting that these factors may influence risk through other mechanisms.
| S-EPMC5159268 | biostudies-literature
Project description:BACKGROUND:Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer. The objective of the current study was to investigate the potential of circulating cell-free miRNAs as biomarkers for colorectal cancer (CRC) and its precursor lesion, colorectal adenoma. METHODS:The serum levels of 800 miRNAs were assessed in a discovery set of 21 patients with CRC, 19 patients with adenoma, and 21 healthy controls using the NanoString miRNA analysis platform. Significantly differentially expressed miRNAs were examined further in a validation cohort of 34 patients with CRC, 33 patients with adenoma, and 35 healthy controls using Fluidigm quantitative polymerase chain reaction assays. RESULTS:The ratios between the expression values of the differentially expressed miRNAs were computed. Three miRNA ratios (miR-17-5p/miR-135b, miR-92a-3p/miR135b, and miR-451a/miR-491-5p) were validated for discriminating patients with adenoma and those with CRC from the healthy control group, and 5 miRNA ratios (let-7b/miR-367-3p, miR-130a-3p/miR-409-3p, miR-148-3p/miR-27b, miR-148a-3p/miR-409-3p, and miR-21-5p/miR-367-3p) were validated for discriminating patients with CRC from those with adenoma and healthy controls. The area under the receiver operating characteristic curve values for the 3 miRNA ratios in discriminating patients with adenoma from healthy controls were 0.831 and 0.735, respectively, in the discovery and validation sets. The area under the receiver operating characteristic curve values for the 5 miRNA ratios in discriminating patients with CRC from those with adenoma were 0.797 and 0.732, respectively, in the discovery and validation sets. Pathway analysis revealed that target genes regulated by the miRNAs from the miRNA ratios were enriched mainly in metabolism-related and inflammation-related pathways. CONCLUSIONS:The data from the current study suggest that circulating miRNAs can distinguish patients with CRC and those with adenoma and may represent novel biomarkers for the early, noninvasive detection of CRC. Cancer 2018;124:785-96. © 2017 American Cancer Society.
| S-EPMC5801195 | biostudies-literature
Project description:Background & aimsLifestyle and dietary risk factors for diverticulitis also have been associated with chronic inflammation. We performed a prospective study of associations among the inflammatory potential of diets, circulating markers of inflammation, and the incidence of diverticulitis.MethodsWe followed 46,418 men, initially free of diverticulitis, from 1986 through 2014 in the Health Professionals Follow-Up Study. We collected data on empiric dietary inflammatory pattern scores, which indicate the inflammatory potential of diets, and determined their association with the risk of incident diverticulitis using Cox proportional hazards regression. We used blood samples provided by 18,225 participants from 1993 through 1995 to conduct a nested case-control study; we used conditional logistic regression to evaluate prediagnostic plasma levels of markers of inflammation, including C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor-receptor superfamily member 1B, in 310 diverticulitis cases and 310 matched diverticulitis-free individuals (controls).ResultsWe documented 1110 cases of incident diverticulitis over 992,589 person-years of follow-up. Compared with participants in the lowest quintile of empiric dietary inflammatory pattern scores, men in the highest quintile had a multivariable-adjusted hazard ratio for diverticulitis of 1.31 (95% CI, 1.07-1.60; Ptrend = .01). The association did not differ significantly by strata of body mass index or vigorous activity (P for interaction > .05 for each). In the nested case-control study, plasma levels of CRP and IL6 were associated with risk of diverticulitis. When we compared extreme quintiles, the multivariable-adjusted relative risk for diverticulitis was 1.85 for CRP (95% CI, 1.04-3.30) and 2.04 for IL6 (95% CI, 1.09-3.84).ConclusionsIn a large prospective cohort of men, we found that the inflammatory potential of diet and prediagnostic plasma levels of markers of inflammation were associated with incident diverticulitis.
| S-EPMC7310666 | biostudies-literature