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AS482 - Serologic inflammatory markers and esophageal adenocarcinoma risk

AS482 - Serologic inflammatory markers and esophageal adenocarcinoma risk

[This page is intended to provide a study summary, the sections of which are below. Please complete these sections, as applicable. The headings below are suggested headings. You can remove inapplicable sections, or add new ones relevant to your study]

Investigator Names and Contact Information

Michael Cook []




The direct mechanical effect of central obesity on esophageal adenocarcinoma risk is widely hypothesized; central adiposity amplifies intra-gastric pressure and disturbs normal sphincter function, culminating in a higher propensity for gastroesophageal reflux disease (GERD) and subsequent increased risk of adenocarcinoma (Corley, 2006; Cook, 2008). However, evidence is accumulating for an indirect effect of central adiposity in relation to the risk of esophageal adenocarcinoma (Reid, 2010; Shaheen, 2013). Indeed, metabolic syndrome—which is a constellation of factors that contribute to a heightened systemic inflammatory state—has been previously associated with various cancers as well as esophageal adenocarcinogenesis (Esposito, 2012; Drahos, 2016a; Drahos, 2016b). In addition, many of the known or suspected risk factors for esophageal adenocarcinoma, including smoking, alcohol and obesity, share a common suspected inflammatory etiology (Reid, 2010; Cook, 2013; Shaheen, 2013). From our studies, we have observed that increased adiposity was associated with Barrett's esophagus and esophageal adenocarcinoma, and these estimates were not attenuated when adjusted for, or stratified by, GERD symptoms (Hoyo, 2012; Kubo, 2013). In addition, in individuals without a history of GERD symptoms increasing BMI remained associated with esophageal adenocarcinoma risk, suggesting an indirect carcinogenic effect. Moreover, the relationship between BMI and esophageal adenocarcinoma has been found to be stronger in men without reflux compared to women without reflux, and this may be due to the fact that visceral fat has a higher metabolic rate and is more common in men than women (Beddy, 2010; Nelsen, 2012). This may be interpreted as further evidence for an indirect proinflammatory route of association emanating from highly metabolic visceral fat, and may provide clues to the enigmatic male predominance of esophageal adenocarcinoma with a sex ratio as high as 8:1(Cook, 2005; Cook, 2009). Therefore we hypothesize that a mechanistic link between obesity and risk of esophageal adenocarcinoma may be related to the proinflammatory effects associated with an excess of adipose tissue and propose to test this hypothesis by quantitation of systemic inflammation markers using prediagnostic serum of individuals who were subsequently diagnosed with esophageal adenocarcinoma by combining seven prospective cohort studies.




1. To evaluate the association of pre-diagnostic circulating inflammation markers with incident esophageal adenocarcinoma.


2. To evaluate body mass index and waist circumference as potential effect modifiers for the relationships of inflammation markers with incident esophageal adenocarcinoma.