Data from High Levels of Aberrant DNA Methylation in <i>Helicobacter pylori</i>–Infected Gastric Mucosae and its Possible Association with Gastric Cancer Risk

Abstract

<div>Abstract<p><b>Introduction:</b> Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by <i>Helicobacter pylori</i>, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of <i>H. pylori</i> infection on the quantity of methylated DNA molecules in noncancerous gastric mucosae and examined its association with gastric cancer risk.</p><p><b>Experimental Design:</b> Gastric mucosae were collected from 154 healthy volunteers (56 <i>H. pylori</i> negative and 98 <i>H. pylori</i> positive) and 72 cases with differentiated-type gastric cancers (29 <i>H. pylori</i> negative and 43 <i>H. pylori</i> positive) by endoscopy. The numbers of DNA molecules methylated and unmethylated for eight regions of seven CpG islands (CGI) were quantified by quantitative PCR after bisulfite modification, and fractions of methylated molecules (methylation levels) were calculated.</p><p><b>Results:</b> Among healthy volunteers, methylation levels of all the eight regions were 5.4- to 303-fold higher in <i>H. pylori</i> positives than in <i>H. pylori</i> negatives (<i>P</i> < 0.0001). Methylation levels of the <i>LOX, HAND1</i>, and <i>THBD</i> promoter CGIs and <i>p41ARC</i> exonic CGI were as high as 7.4% or more in <i>H. pylori</i>–positive individuals. Among <i>H. pylori</i>–negative individuals, methylation levels of all the eight regions were 2.2- to 32-fold higher in gastric cancer cases than in age-matched healthy volunteers (<i>P</i> ≤ 0.01). Among <i>H. pylori</i>–positive individuals, methylation levels were highly variable, and that of only <i>HAND1</i> was significantly increased in gastric cancer cases (1.4-fold, <i>P</i> = 0.02).</p><p><b>Conclusions:</b> It was indicated that <i>H. pylori</i> infection potently induces methylation of CGIs to various degrees. Methylation levels of specific CGIs seemed to reflect gastric cancer risk in <i>H. pylori</i>–negative individuals.</p></div>