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Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk Stratification.

ABSTRACT: We conducted two independent nested case-control studies to identify circulating inflammation markers reproducibly associated with lung cancer risk and to investigate the utility of replicated markers for lung cancer risk stratification.Nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the previously published discovery study included 526 lung cancer patients and 592 control subjects and the replication study included 526 lung cancer case patients and 625 control subjects. Control subjects were matched by sex, age, smoking, study visit, and years of blood draw and exit. Serum levels of 51 inflammation markers were measured. Odds ratios (ORs) were estimated with conditional logistic regression. All statistical tests were two-sided.Of 11 markers identified in the discovery study, C-reactive protein (CRP) (odds ratio [OR] [highest vs. lowest category] = 1.77, 95% confidence interval [CI] = 1.23 to 2.54), serum amyloid A (SAA) (OR = 1.88, 95% CI = 1.28 to 2.76), soluble tumor necrosis factor receptor-2 (sTNFRII) (OR = 1.70, 95% CI = 1.18 to 2.45), and monokine induced by gamma interferon (CXCL9/MIG) (OR = 2.09, 95% CI = 1.41 to 3.00) were associated with lung cancer risk in the replication study (P trend < .01). In pooled analyses, CRP, SAA, and CXCL9/MIG remained associated with lung cancer more than six years before diagnosis (P trend < .05). The incorporation of an inflammation score combining these four markers did not improve the sensitivity (77.6% vs 75.8%, P = .33) or specificity (56.1% vs 56.1%, P = .98) of risk-based lung cancer models.Circulating levels of CRP, SAA, sTNFRII, and CXCL9/MIG were reproducibly associated with lung cancer risk in two independent studies within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, underscoring an etiologic role for inflammation in lung carcinogenesis, though replication is needed in other populations. Markers did not improve lung cancer risk stratification beyond standard demographic and behavioral characteristics.

SUBMITTER: Shiels MS

PROVIDER: S-EPMC5964716 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk Stratification.

Shiels Meredith S MS Katki Hormuzd A HA Hildesheim Allan A Pfeiffer Ruth M RM Engels Eric A EA Williams Marcus M Kemp Troy J TJ Caporaso Neil E NE Pinto Ligia A LA Chaturvedi Anil K AK

Journal of the National Cancer Institute 20150728 10

<h4>Background</h4>We conducted two independent nested case-control studies to identify circulating inflammation markers reproducibly associated with lung cancer risk and to investigate the utility of replicated markers for lung cancer risk stratification.<h4>Methods</h4>Nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the previously published discovery study included 526 lung cancer patients and 592 control subjects and the replication study included 526 lung ca ...[more]

PMID: 26220734

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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: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.

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Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk Stratification.

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Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk Stratification.

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