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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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 |
doi_str_mv | 10.1111/j.1349-7006.2010.01535.x |
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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 < 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 < 0.05). Hypermethylation of THBD, and possibly p16, was significantly associated with GC, regardless of the status of current H. pylori infection (all P < 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)</description><identifier>ISSN: 1347-9032</identifier><identifier>ISSN: 1349-7006</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/j.1349-7006.2010.01535.x</identifier><identifier>PMID: 20345486</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>Cancer science, 2010-06, Vol.101 (6), p.1337-1346</ispartof><rights>2010 Japanese Cancer Association</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6555-7ef12b041c7e31163f6fa15d64808727581217de3b4ce0bea193e90d53909daa3</citedby><cites>FETCH-LOGICAL-c6555-7ef12b041c7e31163f6fa15d64808727581217de3b4ce0bea193e90d53909daa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11159191/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11159191/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1349-7006.2010.01535.x$$EView_record_in_Wiley-Blackwell$$FView_record_in_$$GWiley-Blackwell</linktorsrc><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22914838$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20345486$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shin, Cheol Min</creatorcontrib><creatorcontrib>Kim, Nayoung</creatorcontrib><creatorcontrib>Jung, Younmu</creatorcontrib><creatorcontrib>Park, Ji Hyun</creatorcontrib><creatorcontrib>Kang, Gyeong Hoon</creatorcontrib><creatorcontrib>Kim, Joo Sung</creatorcontrib><creatorcontrib>Jung, Hyun Chae</creatorcontrib><creatorcontrib>Song, In Sung</creatorcontrib><title>Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><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 < 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 < 0.05). Hypermethylation of THBD, and possibly p16, was significantly associated with GC, regardless of the status of current H. pylori infection (all P < 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)</description><subject>adenomatous polyposis coli</subject><subject>Adult</subject><subject>Aged</subject><subject>Bacterial diseases</subject><subject>Bacterial diseases of the digestive system and abdomen</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Carcinogenesis</subject><subject>CpG islands</subject><subject>DNA Methylation</subject><subject>Dysplasia</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastritis</subject><subject>Gastritis - etiology</subject><subject>Gastritis - genetics</subject><subject>Genes, APC</subject><subject>Guanylate cyclase</subject><subject>Helicobacter Infections - complications</subject><subject>Helicobacter pylori</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Infection</subject><subject>Infectious diseases</subject><subject>Intestine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metaplasia</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Polymerase chain reaction</subject><subject>Precancerous Conditions - etiology</subject><subject>Precancerous Conditions - genetics</subject><subject>Stomach Neoplasms - etiology</subject><subject>Stomach Neoplasms - genetics</subject><subject>Thrombomodulin - genetics</subject><subject>Tumors</subject><issn>1347-9032</issn><issn>1349-7006</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUtvEzEUhUeIipbCX0DeIFYT7PFrvEAoCi1FqorEY215PHcSR55xsCe0-ff1JCHArt74yue7x9c-RYEInpG83q9nhDJVSozFrML5FBNO-ezhWXFxEp7va1kqTKvz4mVKa4ypYIq9KM4rTBlntbgoVt-CBxQ6dAPe2dAYO0JEm50P0SE3dGBHF4ZcIdNAjGYY0ae7OephXO282WvGh2GJ-q0fXRphg5YmjdFZZE20bghLGCC59Ko464xP8Pq4XxY_r69-LG7K26-fvyzmt6UVnPNSQkeqBjNiJVBCBO1EZwhvBatxLSvJa1IR2QJtmAXcgCGKgsItpwqr1hh6WXw8-G62TQ-thWGMxutNdL2JOx2M0_8rg1vpZfit879yRRTJDu-ODjH82kIade-SBe_NAGGbtGS14lgy9gSSCaK44JmsD6SNIaUI3WkggqebiV7rKTk9JaenSPU-Uv2QW9_8-6BT458MM_D2CJhkje9ySNalv1ylCKtpnbkPB-7eedg9eQC9mH-fKvoIqNa-MA</recordid><startdate>201006</startdate><enddate>201006</enddate><creator>Shin, Cheol Min</creator><creator>Kim, Nayoung</creator><creator>Jung, Younmu</creator><creator>Park, Ji Hyun</creator><creator>Kang, Gyeong Hoon</creator><creator>Kim, Joo Sung</creator><creator>Jung, Hyun Chae</creator><creator>Song, In Sung</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7TM</scope><scope>C1K</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201006</creationdate><title>Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis</title><author>Shin, Cheol Min ; Kim, Nayoung ; Jung, Younmu ; Park, Ji Hyun ; Kang, Gyeong Hoon ; Kim, Joo Sung ; Jung, Hyun Chae ; Song, In Sung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6555-7ef12b041c7e31163f6fa15d64808727581217de3b4ce0bea193e90d53909daa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>adenomatous polyposis coli</topic><topic>Adult</topic><topic>Aged</topic><topic>Bacterial diseases</topic><topic>Bacterial diseases of the digestive system and abdomen</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Carcinogenesis</topic><topic>CpG islands</topic><topic>DNA Methylation</topic><topic>Dysplasia</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastritis</topic><topic>Gastritis - etiology</topic><topic>Gastritis - genetics</topic><topic>Genes, APC</topic><topic>Guanylate cyclase</topic><topic>Helicobacter Infections - complications</topic><topic>Helicobacter pylori</topic><topic>Human bacterial diseases</topic><topic>Humans</topic><topic>Infection</topic><topic>Infectious diseases</topic><topic>Intestine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metaplasia</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Polymerase chain reaction</topic><topic>Precancerous Conditions - etiology</topic><topic>Precancerous Conditions - genetics</topic><topic>Stomach Neoplasms - etiology</topic><topic>Stomach Neoplasms - genetics</topic><topic>Thrombomodulin - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shin, Cheol Min</creatorcontrib><creatorcontrib>Kim, Nayoung</creatorcontrib><creatorcontrib>Jung, Younmu</creatorcontrib><creatorcontrib>Park, Ji Hyun</creatorcontrib><creatorcontrib>Kang, Gyeong Hoon</creatorcontrib><creatorcontrib>Kim, Joo Sung</creatorcontrib><creatorcontrib>Jung, Hyun Chae</creatorcontrib><creatorcontrib>Song, In Sung</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nucleic Acids Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Shin, Cheol Min</au><au>Kim, Nayoung</au><au>Jung, Younmu</au><au>Park, Ji Hyun</au><au>Kang, Gyeong Hoon</au><au>Kim, Joo Sung</au><au>Jung, Hyun Chae</au><au>Song, In Sung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2010-06</date><risdate>2010</risdate><volume>101</volume><issue>6</issue><spage>1337</spage><epage>1346</epage><pages>1337-1346</pages><issn>1347-9032</issn><issn>1349-7006</issn><eissn>1349-7006</eissn><abstract>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 < 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 < 0.05). Hypermethylation of THBD, and possibly p16, was significantly associated with GC, regardless of the status of current H. pylori infection (all P < 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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