Su1993 Somatic Mutations in the Mismatch Repair System Are Responsible for a Majority of Unexplained Lynch Syndrome Cases: Time to Revise Lynch Syndrome Screening?
2015
G A A b st ra ct s gastric tissue samples harvested from an independent population ofH. pylori-infected persons in New Orleans to assess expression and methylation status of HIF-1α in vivo. Gastric tissue specimens from African-American subjects harboring an increased risk for gastric cancer exhibited marked decreases in methylation of HIF-1α with increasing disease severity. The highest levels of HIF-1α methylation were found in patients with non-
atrophic gastritisand this decreased as disease progressed to
atrophic gastritis(0.5-fold) and
intestinal metaplasia(0.2-fold), versus
gastritisalone. Consistent with decreasing HIF-1α methylation status, gastric tissue from African-American patients harbored increased levels of HIF-1α expression with increasing disease progression and this was not observed in Caucasian patients. Collectively, these data indicate that H. pylori induces HIF-1α in gastric epithelial cells and this is augmented under conditions of iron deficiency. HIF-1α expression in vivo increases in conjunction with decreased HIF-1α methylation and the development of
premalignant lesions, which may provide a mechanism underpinning the link between high altitude, iron depletion, and increased gastric cancer rates within the context of H. pylori infection.
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