July 15, 2019

Biomarkers of inflammation in serum and risk of esophageal adenocarcinoma

Dr. Michael Cook and colleagues at NCI report that certain markers of inflammation in blood are associated with esophageal adenocarcinoma, and conclude that systemic inflammation may underlie some of the increased risk with obesity and cigarette smoking.

Biomarkers of inflammation in serum and risk of esophageal adenocarcinoma

Gut. 2019 Jun;68(6):960-968. doi: 10.1136/gutjnl-2018-316678. Epub  2018 Aug 18.

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

Cook MB1, Barnett MJ2, Bock CH3, Cross AJ4, Goodman PJ5, Goodman GE2,6, Haiman CA7, Khaw KT8, McCullough ML9, Newton CC9, Boutron-Ruault MC10,11, Lund E12, Rutegård M13, Thornquist MD2, Spriggs M14, Giffen C14, Freedman ND1, Kemp T15, Kroenke CH16, Le Marchand L17, Park JY18, Simon M3, Wilkens LR16, Pinto L14, Hildesheim A1, Campbell PT9.

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) (ORsquartile 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.