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Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21
Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein,...
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| Published in: | Cancer science 2018-12, Vol.109 (12), p.4015-4024 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| container_end_page | 4024 |
| container_issue | 12 |
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| container_title | Cancer science |
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| creator | Tanikawa, Chizu Kamatani, Yoichiro Toyoshima, Osamu Sakamoto, Hiromi Ito, Hidemi Takahashi, Atsushi Momozawa, Yukihide Hirata, Makoto Fuse, Nobuo Takai‐Igarashi, Takako Shimizu, Atsushi Sasaki, Makoto Yamaji, Taiki Sawada, Norie Iwasaki, Motoki Tsugane, Shoichiro Naito, Mariko Hishida, Asahi Wakai, Kenji Furusyo, Norihiro Murakami, Yoshinori Nakamura, Yusuke Imoto, Issei Inazawa, Johji Oze, Isao Sato, Naomi Tanioka, Fumihiko Sugimura, Haruhiko Hirose, Hiroshi Yoshida, Teruhiko Matsuo, Keitaro Kubo, Michiaki Matsuda, Koichi |
| description | Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large‐scale genome‐wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11‐12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.
Manhattan plot of gastric cancer GWAS. |
| doi_str_mv | 10.1111/cas.13815 |
| format | article |
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Manhattan plot of gastric cancer GWAS.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.13815</identifier><identifier>PMID: 30281874</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>ABO ; ABO Blood-Group System - genetics ; Adult ; Aged ; Aged, 80 and over ; beta-Defensins - genetics ; Biopsy ; Blood groups ; Case-Control Studies ; Chromosome 12 ; Chromosome 9 ; Chromosomes, Human, Pair 12 - genetics ; Chromosomes, Human, Pair 20 - genetics ; Chromosomes, Human, Pair 9 - genetics ; Collaboration ; CUX2 ; DEFB ; Disease ; Female ; Gastric cancer ; Gene expression ; Gene Expression Regulation ; Genetic diversity ; Genetic factors ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study - methods ; Genomes ; genome‐wide association study ; Health risk assessment ; Helicobacter Infections - genetics ; Homeodomain Proteins - genetics ; Humans ; Infections ; Japan ; Male ; Medical research ; Middle Aged ; Mucosa ; Original ; Polymorphism ; Polymorphism, Single Nucleotide ; Population ; Principal components analysis ; Public health ; Stomach Neoplasms - genetics ; Stomach Neoplasms - microbiology ; Studies ; Young Adult</subject><ispartof>Cancer science, 2018-12, Vol.109 (12), p.4015-4024</ispartof><rights>2018 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5335-60ac79cf606b2e97b9594a83dabdb9ff47bfcb2bd53d102fe637eb4a718cae283</citedby><cites>FETCH-LOGICAL-c5335-60ac79cf606b2e97b9594a83dabdb9ff47bfcb2bd53d102fe637eb4a718cae283</cites><orcidid>0000-0001-7292-2686 ; 0000-0002-4150-7938 ; 0000-0002-0779-3088 ; 0000-0003-1761-6314 ; 0000-0002-0762-1147 ; 0000-0002-9936-1476 ; 0000-0002-3945-2800</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2287983077/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2287983077?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,11589,25783,27957,27958,37047,44625,46087,46511,53827,53829,75483</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30281874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanikawa, Chizu</creatorcontrib><creatorcontrib>Kamatani, Yoichiro</creatorcontrib><creatorcontrib>Toyoshima, Osamu</creatorcontrib><creatorcontrib>Sakamoto, Hiromi</creatorcontrib><creatorcontrib>Ito, Hidemi</creatorcontrib><creatorcontrib>Takahashi, Atsushi</creatorcontrib><creatorcontrib>Momozawa, Yukihide</creatorcontrib><creatorcontrib>Hirata, Makoto</creatorcontrib><creatorcontrib>Fuse, Nobuo</creatorcontrib><creatorcontrib>Takai‐Igarashi, Takako</creatorcontrib><creatorcontrib>Shimizu, Atsushi</creatorcontrib><creatorcontrib>Sasaki, Makoto</creatorcontrib><creatorcontrib>Yamaji, Taiki</creatorcontrib><creatorcontrib>Sawada, Norie</creatorcontrib><creatorcontrib>Iwasaki, Motoki</creatorcontrib><creatorcontrib>Tsugane, Shoichiro</creatorcontrib><creatorcontrib>Naito, Mariko</creatorcontrib><creatorcontrib>Hishida, Asahi</creatorcontrib><creatorcontrib>Wakai, Kenji</creatorcontrib><creatorcontrib>Furusyo, Norihiro</creatorcontrib><creatorcontrib>Murakami, Yoshinori</creatorcontrib><creatorcontrib>Nakamura, Yusuke</creatorcontrib><creatorcontrib>Imoto, Issei</creatorcontrib><creatorcontrib>Inazawa, Johji</creatorcontrib><creatorcontrib>Oze, Isao</creatorcontrib><creatorcontrib>Sato, Naomi</creatorcontrib><creatorcontrib>Tanioka, Fumihiko</creatorcontrib><creatorcontrib>Sugimura, Haruhiko</creatorcontrib><creatorcontrib>Hirose, Hiroshi</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Matsuo, Keitaro</creatorcontrib><creatorcontrib>Kubo, Michiaki</creatorcontrib><creatorcontrib>Matsuda, Koichi</creatorcontrib><title>Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large‐scale genome‐wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11‐12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.
Manhattan plot of gastric cancer GWAS.</description><subject>ABO</subject><subject>ABO Blood-Group System - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>beta-Defensins - genetics</subject><subject>Biopsy</subject><subject>Blood groups</subject><subject>Case-Control Studies</subject><subject>Chromosome 12</subject><subject>Chromosome 9</subject><subject>Chromosomes, Human, Pair 12 - genetics</subject><subject>Chromosomes, Human, Pair 20 - genetics</subject><subject>Chromosomes, Human, Pair 9 - genetics</subject><subject>Collaboration</subject><subject>CUX2</subject><subject>DEFB</subject><subject>Disease</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genetic diversity</subject><subject>Genetic factors</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>genome‐wide association study</subject><subject>Health risk assessment</subject><subject>Helicobacter Infections - genetics</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humans</subject><subject>Infections</subject><subject>Japan</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Original</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Principal components analysis</subject><subject>Public health</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - microbiology</subject><subject>Studies</subject><subject>Young 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Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanikawa, Chizu</au><au>Kamatani, Yoichiro</au><au>Toyoshima, Osamu</au><au>Sakamoto, Hiromi</au><au>Ito, Hidemi</au><au>Takahashi, Atsushi</au><au>Momozawa, Yukihide</au><au>Hirata, Makoto</au><au>Fuse, Nobuo</au><au>Takai‐Igarashi, Takako</au><au>Shimizu, Atsushi</au><au>Sasaki, Makoto</au><au>Yamaji, Taiki</au><au>Sawada, Norie</au><au>Iwasaki, Motoki</au><au>Tsugane, Shoichiro</au><au>Naito, Mariko</au><au>Hishida, Asahi</au><au>Wakai, Kenji</au><au>Furusyo, Norihiro</au><au>Murakami, Yoshinori</au><au>Nakamura, Yusuke</au><au>Imoto, Issei</au><au>Inazawa, Johji</au><au>Oze, Isao</au><au>Sato, Naomi</au><au>Tanioka, Fumihiko</au><au>Sugimura, Haruhiko</au><au>Hirose, Hiroshi</au><au>Yoshida, Teruhiko</au><au>Matsuo, Keitaro</au><au>Kubo, Michiaki</au><au>Matsuda, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2018-12</date><risdate>2018</risdate><volume>109</volume><issue>12</issue><spage>4015</spage><epage>4024</epage><pages>4015-4024</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large‐scale genome‐wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11‐12 (rs6490061, P = 3.20 × 10−8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.
Manhattan plot of gastric cancer GWAS.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>30281874</pmid><doi>10.1111/cas.13815</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7292-2686</orcidid><orcidid>https://orcid.org/0000-0002-4150-7938</orcidid><orcidid>https://orcid.org/0000-0002-0779-3088</orcidid><orcidid>https://orcid.org/0000-0003-1761-6314</orcidid><orcidid>https://orcid.org/0000-0002-0762-1147</orcidid><orcidid>https://orcid.org/0000-0002-9936-1476</orcidid><orcidid>https://orcid.org/0000-0002-3945-2800</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2018-12, Vol.109 (12), p.4015-4024 |
| issn | 1347-9032 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6272082 |
| source | Open Access: PubMed Central; Wiley-Blackwell Titles (Open access); Publicly Available Content Database |
| subjects | ABO ABO Blood-Group System - genetics Adult Aged Aged, 80 and over beta-Defensins - genetics Biopsy Blood groups Case-Control Studies Chromosome 12 Chromosome 9 Chromosomes, Human, Pair 12 - genetics Chromosomes, Human, Pair 20 - genetics Chromosomes, Human, Pair 9 - genetics Collaboration CUX2 DEFB Disease Female Gastric cancer Gene expression Gene Expression Regulation Genetic diversity Genetic factors Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study - methods Genomes genome‐wide association study Health risk assessment Helicobacter Infections - genetics Homeodomain Proteins - genetics Humans Infections Japan Male Medical research Middle Aged Mucosa Original Polymorphism Polymorphism, Single Nucleotide Population Principal components analysis Public health Stomach Neoplasms - genetics Stomach Neoplasms - microbiology Studies Young Adult |
| title | Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21 |
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