Dataset Information

Circulating inflammatory markers and colorectal cancer risk: A prospective case-cohort study in Japan.

ABSTRACT: Blood levels of inflammation-related markers may reveal molecular pathways contributing to carcinogenesis. To date, prospective associations with colorectal cancer (CRC) risk have been based on few studies with limited sets of analytes. We conducted a case-cohort study within the Japan Public Health Center-based Prospective Study Cohort II, comparing 457 incident CRC cases during median 18 years follow-up with a random subcohort of 774 individuals. Baseline plasma levels of 62 cytokines, soluble receptors, acute-phase proteins, and growth factor markers were measured using Luminex bead-based assays. We estimated hazard ratios (HRs) associating each marker with CRC risk by Cox proportional hazards models adjusted for potential confounders. Subanalyses compared cases by years after blood draw (<5 vs. ?5) and anatomical subsite (colon vs. rectum). Linear trends in quantiles of four C-C motif ligand (CCL) chemokines, one C-X-C motif ligand (CXCL) chemokine, and a soluble receptor were nominally associated with CRC risk based on ptrend < 0.05, but none met false discovery rate corrected statistical significance. HRs for the 4th vs. 1st quartile were: 1.69 for CCL2/MCP1, 1.61 for soluble tumor necrosis factor receptor 2, 1.39 for CCL15/MIP1D, 1.35 for CCL27/CTACK, 0.70 for CXCL6/GCP2 and 0.61 for CCL3/MIP1A. Among cases diagnosed 5+ years after enrollment, CCL2/MCP1, CCL3/MIP1A and CXCL6/GCP2 retained nominal statistical significance. There were no significant differences in associations between colon and rectum. Our findings implicate chemokine alterations in colorectal carcinogenesis, but require replication for confirmation. Noninvasive chemokine assays may have potential application in colorectal cancer screening and etiologic research.

SUBMITTER: Song M

PROVIDER: S-EPMC6235711 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Circulating inflammatory markers and colorectal cancer risk: A prospective case-cohort study in Japan.

Song Minkyo M Sasazuki Shizuka S Camargo M Constanza MC Shimazu Taichi T Charvat Hadrien H Yamaji Taiki T Sawada Norie N Kemp Troy J TJ Pfeiffer Ruth M RM Hildesheim Allan A Pinto Ligia A LA Rabkin Charles S CS Tsugane Shoichiro S

International journal of cancer 20181009 11

Blood levels of inflammation-related markers may reveal molecular pathways contributing to carcinogenesis. To date, prospective associations with colorectal cancer (CRC) risk have been based on few studies with limited sets of analytes. We conducted a case-cohort study within the Japan Public Health Center-based Prospective Study Cohort II, comparing 457 incident CRC cases during median 18 years follow-up with a random subcohort of 774 individuals. Baseline plasma levels of 62 cytokines, soluble ...[more]

PMID: 30132835

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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.

Project description:BackgroundMajor abdominal surgery, including colorectal cancer (CRC) surgery, leads to systemic inflammatory response syndrome that can be detected and monitored with inflammatory markers testing. The aims of the study were to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) in following the inflammatory response in CRC surgery and postoperative period, as well as to determine if duration of the surgery and the time that the colon has been opened during the surgery (open colon time [OCT]) reflect a larger surgical stress through inflammatory markers rise.MethodsThe study included 20 patients who underwent CRC surgery and 19 healthy volunteers from June 2011 to September 2012. We determined inflammatory markers 1 day before surgery (T0), 24 h (T1), 48 h (T2), and 7 days after the surgery (T3). All statistical analyses were calculated using MedCalc Statistical Software version 14.8.1 (MedCalc Software bvba, Ostend, Belgium).ResultsConcentrations of CRP, PCT, and IL-6 in all measurement times were statistically different and sTREM-1 did not yield statistical significance. A weak positive correlation was found between IL-6 in T1 and T2 with the duration of the surgery (T1: r = 0.4060, P < 0.0001; T2: r = 0.3430, P < 0.0001) and OCT (T1: r = 0.3640, P < 0.0001, T2: r = 0.3430, P < 0.0001). A weak positive correlation between CRP in T2 and OCT (r = 0.4210, P < 0.0001) was also found. The interconnectivity of tested parameters showed a weak positive correlation between CRP and IL-6 in T1 (r = 0.3680; P < 0.0001), moderate positive correlation in T2 (r = 0.6770; P < 0.0001), and a strong positive correlation in T3 (r = 0.8651; P < 0.0001).ConclusionsCRP, IL-6, and PCT were shown to be reliable for postoperative monitoring. Simultaneous determination of CRP and IL-6 might not be useful as they follow similar kinetics. sTREM-1 might not be useful in CRC postoperative monitoring.Trial registrationwww.ClinicalTrials.gov, NCT01244022;https://www.clinicaltrials.gov/ct2/show/NCT01244022?term=01244022&rank=1.

Dataset Information

Circulating inflammatory markers and colorectal cancer risk: A prospective case-cohort study in Japan.

Publications

Circulating inflammatory markers and colorectal cancer risk: A prospective case-cohort study in Japan.

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