Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis

CpG island hypermethylation is frequently found during gastric carcinogenesis. We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six ge...

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Veröffentlicht in:Cancer science 2010-06, Vol.101 (6), p.1337-1346
Hauptverfasser: Shin, Cheol Min, Kim, Nayoung, Jung, Younmu, Park, Ji Hyun, Kang, Gyeong Hoon, Kim, Joo Sung, Jung, Hyun Chae, Song, In Sung
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container_end_page 1346
container_issue 6
container_start_page 1337
container_title Cancer science
container_volume 101
creator Shin, Cheol Min
Kim, Nayoung
Jung, Younmu
Park, Ji Hyun
Kang, Gyeong Hoon
Kim, Joo Sung
Jung, Hyun Chae
Song, In Sung
description CpG island hypermethylation is frequently found during gastric carcinogenesis. We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six genes were evaluated in noncancerous gastric biopsy specimens using quantitative methylation‐specific PCR in 459 patients with gastric cancer (GC), 137 with dysplasia, and 248 controls. Controls were divided into four subgroups sorted by current H. pylori infection status (active vs past or negative infection) and the presence of intestinal metaplasia (IM). In controls, active H. pylori infection significantly increased methylation levels in THBD, LOX, and HAND1 (all P 
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We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six genes were evaluated in noncancerous gastric biopsy specimens using quantitative methylation‐specific PCR in 459 patients with gastric cancer (GC), 137 with dysplasia, and 248 controls. Controls were divided into four subgroups sorted by current H. pylori infection status (active vs past or negative infection) and the presence of intestinal metaplasia (IM). In controls, active H. pylori infection significantly increased methylation levels in THBD, LOX, and HAND1 (all P &lt; 0.001), and hypermethylation of THBD, HAND1, and APC was associated with IM. Aberrant DNA hypermethylation was correlated well with activity of H. pylori‐associated gastritis. However, methylation levels in LOX, HAND1, THBD, and p41ARC remained increased in cases with past H. pylori infection compared to those that were H. pylori negative (all P &lt; 0.05). Hypermethylation of THBD, and possibly p16, was significantly associated with GC, regardless of the status of current H. pylori infection (all P &lt; 0.05). These results suggest that aberrant DNA hypermethylation caused by H. pylori‐associated gastritis occurs in a gene‐specific manner along gastric carcinogenesis, which can be persistent even after the disappearance of H. pylori. Aberrant methylation of THBD might provide a link between H. pylori infection and development of GC. 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We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six genes were evaluated in noncancerous gastric biopsy specimens using quantitative methylation‐specific PCR in 459 patients with gastric cancer (GC), 137 with dysplasia, and 248 controls. Controls were divided into four subgroups sorted by current H. pylori infection status (active vs past or negative infection) and the presence of intestinal metaplasia (IM). In controls, active H. pylori infection significantly increased methylation levels in THBD, LOX, and HAND1 (all P &lt; 0.001), and hypermethylation of THBD, HAND1, and APC was associated with IM. Aberrant DNA hypermethylation was correlated well with activity of H. pylori‐associated gastritis. 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We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six genes were evaluated in noncancerous gastric biopsy specimens using quantitative methylation‐specific PCR in 459 patients with gastric cancer (GC), 137 with dysplasia, and 248 controls. Controls were divided into four subgroups sorted by current H. pylori infection status (active vs past or negative infection) and the presence of intestinal metaplasia (IM). In controls, active H. pylori infection significantly increased methylation levels in THBD, LOX, and HAND1 (all P &lt; 0.001), and hypermethylation of THBD, HAND1, and APC was associated with IM. Aberrant DNA hypermethylation was correlated well with activity of H. pylori‐associated gastritis. However, methylation levels in LOX, HAND1, THBD, and p41ARC remained increased in cases with past H. pylori infection compared to those that were H. pylori negative (all P &lt; 0.05). Hypermethylation of THBD, and possibly p16, was significantly associated with GC, regardless of the status of current H. pylori infection (all P &lt; 0.05). These results suggest that aberrant DNA hypermethylation caused by H. pylori‐associated gastritis occurs in a gene‐specific manner along gastric carcinogenesis, which can be persistent even after the disappearance of H. pylori. Aberrant methylation of THBD might provide a link between H. pylori infection and development of GC. (Cancer Sci 2010)</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20345486</pmid><doi>10.1111/j.1349-7006.2010.01535.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects adenomatous polyposis coli
Adult
Aged
Bacterial diseases
Bacterial diseases of the digestive system and abdomen
Basic Helix-Loop-Helix Transcription Factors - genetics
Biological and medical sciences
Biopsy
Carcinogenesis
CpG islands
DNA Methylation
Dysplasia
Female
Gastric cancer
Gastric Mucosa - metabolism
Gastritis
Gastritis - etiology
Gastritis - genetics
Genes, APC
Guanylate cyclase
Helicobacter Infections - complications
Helicobacter pylori
Human bacterial diseases
Humans
Infection
Infectious diseases
Intestine
Male
Medical sciences
Metaplasia
Middle Aged
Original
Polymerase chain reaction
Precancerous Conditions - etiology
Precancerous Conditions - genetics
Stomach Neoplasms - etiology
Stomach Neoplasms - genetics
Thrombomodulin - genetics
Tumors
title Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis
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