Dataset Information

Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium.

ABSTRACT:

Objective

Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.

Design

This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.

Results

Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORs_{quartile 4 vs 1}=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.

Conclusion

This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.

SUBMITTER: Cook MB

PROVIDER: S-EPMC6379150 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium.

Cook Michael B MB Barnett Matthew J MJ Bock Cathryn H CH Cross Amanda J AJ Goodman Phyllis J PJ Goodman Gary E GE Haiman Christopher A CA Khaw Kay-Tee KT McCullough Marjorie L ML Newton Christine C CC Boutron-Ruault Marie-Christine MC Lund Eiliv E Rutegård Martin M Thornquist Mark D MD Spriggs Michael M Giffen Carol C Freedman Neal D ND Kemp Troy T Kroenke Candyce H CH Le Marchand Loïc L Park Jin Young JY Simon Michael M Wilkens Lynne R LR Pinto Ligia L Hildesheim Allan A Campbell Peter T PT

Gut 20180818 6

<h4>Objective</h4>Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.<h4>Design</h4>This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls f ...[more]

PMID: 30121626

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Project description:Background Less than 20 % of patients with resectable oesophageal adenocarcinoma obtain a pathological response following neoadjuvant chemotherapy. Studies using oesophageal cancer cell lines have shown that drug sensitive tumour cells undergo apoptosis in response to drug treatment, whereas resistant cells induce autophagy and can recover following withdrawal of drug. In this study, we evaluated markers of apoptosis (active/cleaved caspase-3) and autophagy (LC3B) to establish whether these markers are useful prognostic indicators following neoadjuvant therapy. Methods Oesophageal adenocarcinoma tumour tissue from the Northern Ireland Biobank at Queens University Belfast was examined retrospectively. Tumours from 144 patients treated with platinum-based neoadjuvant chemotherapy followed by surgical resection were assembled into tissue microarrays prior to immunohistochemical analysis. Kaplan-Meier survival curves and log-rank tests were used to assess the impact of cleaved caspase-3 and LC3B expression on survival. Cox regression was used to examine association with clinical risk factors. Results High levels of cleaved caspase-3 were found in 14.6 % of patients and this correlated with a significantly better overall survival (p = 0.03). 38.9 % of patients had high cytoplasmic LC3B expression, which correlated with poor overall survival (p = 0.041). In addition, a distinct globular pattern of LC3B expression was identified in 40.3 % of patients and was also predictive of overall survival (p < 0.001). LC3B globular structures are also associated with tumour recurrence (p = 0.014). When these markers were assessed in combination, it was found that patients who showed low/negative cleaved caspase-3 staining and high/positive staining for both patterns of LC3B had the worst overall survival (p < 0.001). Multi-variate analysis also indicated that this marker combination was an independent predictor of poor prognosis (p = 0.008; HR = 0.046, 95% CI = (0.005-0.443). Conclusions The expression of cleaved caspase-3 and specific LC3B staining patterns are associated with overall survival following neoadjuvant treatment. The combination of these markers is an independent indicator of outcome in neoadjuvant chemotherapy treated oesophageal adenocarcinoma. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09981-8.

Dataset Information

Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium.

Objective

Design

Results

Conclusion

Publications

Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium.

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