ZIA CP010220 10674 (ZIA) | |||
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Title | CPRD EAC Progression Study | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Cook, Michael | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $13,348 | Project Dates | null - null |
Fiscal Year | 2018 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Esophagus (100.0%) | ||
Research Type | |||
Cancer Progression & Metastasis Endogenous Factors in the Origin and Cause of Cancer |
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Abstract | |||
Barrett?s esophagus is a precancerous lesion that is considered to principally arise as a complication of gastroesophageal reflux disease (GERD) and has the effect of drastically increasing the risk of esophageal adenocarcinoma. Risk factors for esophageal adenocarcinoma include GERD, tobacco smoking, and obesity, although the mechanism of the latter remains unclear. The mechanical effect of obesity is widely accepted, whereby central adiposity amplifies intra-gastric pressure and disturbs normal sphincter function, culminating in a higher propensity for GERD and subsequent increased risk of Barrett?s esophagus. However, evidence suggests that increasing central adiposity also increases risk of Barrett?s esophagus independent of GERD. Related to central adiposity is metabolic syndrome which is a confluence of risk factors known to confer a systemic inflammatory state; a potential indirect mechanism by which obesity could be associated with Barrett?s esophagus. In a recent SEER-Medicare analysis, we demonstrated that metabolic syndrome increased risk of Barrett?s esophagus, an association driven by and confined to the stratum without GERD symptoms. We propose the provocative hypothesis that the direct, proinflammatory effects of GERD cause esophageal tissues to reach a saturated inflammatory state, to which the systemic inflammation of metabolic syndrome has little additional effect negating any relationship to be observed. Conversely, in those without GERD symptoms, systemic (global) inflammation, conferred by metabolic syndrome, increases the risk for normal esophageal tissues to develop metaplasia and eventually cancer. To further investigate these hypotheses and extend upon our recent findings, we have assessed these relationships in the Clinical Practice Research Datalink (CPRD), the manuscript of which was recently published in Cancer Epidemiology. |