Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer
Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a si...
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| Veröffentlicht in: | Nature genetics 2008-06, Vol.40 (6), p.730-740 |
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| creator | Sakamoto, Hiromi Yoshimura, Kimio Saeki, Norihisa Katai, Hitoshi Shimoda, Tadakazu Matsuno, Yoshihiro Saito, Daizo Sugimura, Haruhiko Tanioka, Fumihiko Kato, Shunji Matsukura, Norio Matsuda, Noriko Nakamura, Tsuneya Hyodo, Ichinosuke Nishina, Tomohiro Yasui, Wataru Hirose, Hiroshi Hayashi, Matsuhiko Toshiro, Emi Ohnami, Sumiko Sekine, Akihiro Sato, Yasunori Totsuka, Hirohiko Ando, Masataka Takemura, Ryo Takahashi, Yoriko Ohdaira, Minoru Aoki, Kenichi Honmyo, Izumi Chiku, Suenori Aoyagi, Kazuhiko Sasaki, Hiroki Ohnami, Shumpei Yanagihara, Kazuyoshi Yoon, Kyong-Ah Kook, Myeong-Cherl Lee, Yeon-Su Park, Sook Ryun Kim, Chan Gyoo Choi, Il Ju Yoshida, Teruhiko Nakamura, Yusuke Hirohashi, Setsuo |
| description | Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in
PSCA
(prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38–1.89,
P
= 1.11 × 10
−9
). The association was far less significant in intestinal-type gastric cancer. We found that
PSCA
is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity
in vitro
and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has
r
2
= 0.995,
D
′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33,
P
= 8.01 × 10
−11
). The polymorphism of the
PSCA
gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer. |
| doi_str_mv | 10.1038/ng.152 |
| format | Article |
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PSCA
(prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38–1.89,
P
= 1.11 × 10
−9
). The association was far less significant in intestinal-type gastric cancer. We found that
PSCA
is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity
in vitro
and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has
r
2
= 0.995,
D
′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33,
P
= 8.01 × 10
−11
). The polymorphism of the
PSCA
gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.152</identifier><identifier>PMID: 18488030</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Adenocarcinoma, Mucinous - genetics ; Adenocarcinoma, Mucinous - pathology ; Agriculture ; Alzheimer's disease ; Animal Genetics and Genomics ; Animals ; Antigens, Neoplasm ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer Research ; Carcinoma, Papillary - genetics ; Carcinoma, Papillary - pathology ; Carcinoma, Signet Ring Cell - genetics ; Carcinoma, Signet Ring Cell - pathology ; Case-Control Studies ; Cell Proliferation ; Cells ; CHO Cells ; Cricetinae ; Cricetulus ; Diabetes ; Diagnosis ; Epithelial cells ; Epithelium ; Exons ; Exons - genetics ; Fundamental and applied biological sciences. Psychology ; Gastric cancer ; Gastroenterology. Liver. Pancreas. Abdomen ; Gastrointestinal diseases ; Gene Frequency ; Gene Function ; Gene polymorphism ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic Variation ; Genetics of eukaryotes. Biological and molecular evolution ; Genome, Human - genetics ; Genomics ; GPI-Linked Proteins ; Haplotypes - genetics ; Health aspects ; Human Genetics ; Humans ; Immunoenzyme Techniques ; Intestinal Neoplasms ; Intestine ; Japan ; Korea ; Linkage Disequilibrium ; Medical sciences ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Mice ; Mortality ; Mutation ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Odds Ratio ; Physiological aspects ; Polymorphism, Single Nucleotide - genetics ; Promoter Regions, Genetic ; Prostate ; Prostate-specific antigen ; Reverse Transcriptase Polymerase Chain Reaction ; Risk factors ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Stem cells ; Stomach cancer ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Studies ; Transcription ; Transcription, Genetic ; Tumors</subject><ispartof>Nature genetics, 2008-06, Vol.40 (6), p.730-740</ispartof><rights>Springer Nature America, Inc. 2008</rights><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-379cff8fc6bd1aead2bc3e64c9ed36d379c4890ad5e1c0d4d8ee47373fcf3d563</citedby><cites>FETCH-LOGICAL-c532t-379cff8fc6bd1aead2bc3e64c9ed36d379c4890ad5e1c0d4d8ee47373fcf3d563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.152$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.152$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20435091$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18488030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakamoto, Hiromi</creatorcontrib><creatorcontrib>Yoshimura, Kimio</creatorcontrib><creatorcontrib>Saeki, Norihisa</creatorcontrib><creatorcontrib>Katai, Hitoshi</creatorcontrib><creatorcontrib>Shimoda, Tadakazu</creatorcontrib><creatorcontrib>Matsuno, Yoshihiro</creatorcontrib><creatorcontrib>Saito, Daizo</creatorcontrib><creatorcontrib>Sugimura, Haruhiko</creatorcontrib><creatorcontrib>Tanioka, Fumihiko</creatorcontrib><creatorcontrib>Kato, Shunji</creatorcontrib><creatorcontrib>Matsukura, Norio</creatorcontrib><creatorcontrib>Matsuda, Noriko</creatorcontrib><creatorcontrib>Nakamura, Tsuneya</creatorcontrib><creatorcontrib>Hyodo, Ichinosuke</creatorcontrib><creatorcontrib>Nishina, Tomohiro</creatorcontrib><creatorcontrib>Yasui, Wataru</creatorcontrib><creatorcontrib>Hirose, Hiroshi</creatorcontrib><creatorcontrib>Hayashi, Matsuhiko</creatorcontrib><creatorcontrib>Toshiro, Emi</creatorcontrib><creatorcontrib>Ohnami, Sumiko</creatorcontrib><creatorcontrib>Sekine, Akihiro</creatorcontrib><creatorcontrib>Sato, Yasunori</creatorcontrib><creatorcontrib>Totsuka, Hirohiko</creatorcontrib><creatorcontrib>Ando, Masataka</creatorcontrib><creatorcontrib>Takemura, Ryo</creatorcontrib><creatorcontrib>Takahashi, Yoriko</creatorcontrib><creatorcontrib>Ohdaira, Minoru</creatorcontrib><creatorcontrib>Aoki, Kenichi</creatorcontrib><creatorcontrib>Honmyo, Izumi</creatorcontrib><creatorcontrib>Chiku, Suenori</creatorcontrib><creatorcontrib>Aoyagi, Kazuhiko</creatorcontrib><creatorcontrib>Sasaki, Hiroki</creatorcontrib><creatorcontrib>Ohnami, Shumpei</creatorcontrib><creatorcontrib>Yanagihara, Kazuyoshi</creatorcontrib><creatorcontrib>Yoon, Kyong-Ah</creatorcontrib><creatorcontrib>Kook, Myeong-Cherl</creatorcontrib><creatorcontrib>Lee, Yeon-Su</creatorcontrib><creatorcontrib>Park, Sook Ryun</creatorcontrib><creatorcontrib>Kim, Chan Gyoo</creatorcontrib><creatorcontrib>Choi, Il Ju</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Nakamura, Yusuke</creatorcontrib><creatorcontrib>Hirohashi, Setsuo</creatorcontrib><creatorcontrib>Study Group of Millennium Genome Project for Cancer</creatorcontrib><creatorcontrib>The Study Group of Millennium Genome Project for Cancer</creatorcontrib><title>Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in
PSCA
(prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38–1.89,
P
= 1.11 × 10
−9
). The association was far less significant in intestinal-type gastric cancer. We found that
PSCA
is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity
in vitro
and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has
r
2
= 0.995,
D
′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33,
P
= 8.01 × 10
−11
). The polymorphism of the
PSCA
gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma, Mucinous - genetics</subject><subject>Adenocarcinoma, Mucinous - pathology</subject><subject>Agriculture</subject><subject>Alzheimer's disease</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Antigens, Neoplasm</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Carcinoma, Papillary - genetics</subject><subject>Carcinoma, Papillary - pathology</subject><subject>Carcinoma, Signet Ring Cell - genetics</subject><subject>Carcinoma, Signet Ring Cell - pathology</subject><subject>Case-Control Studies</subject><subject>Cell Proliferation</subject><subject>Cells</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Diabetes</subject><subject>Diagnosis</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Exons</subject><subject>Exons - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastric cancer</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gastrointestinal diseases</subject><subject>Gene Frequency</subject><subject>Gene Function</subject><subject>Gene polymorphism</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome, Human - genetics</subject><subject>Genomics</subject><subject>GPI-Linked Proteins</subject><subject>Haplotypes - genetics</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Intestinal Neoplasms</subject><subject>Intestine</subject><subject>Japan</subject><subject>Korea</subject><subject>Linkage Disequilibrium</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Mortality</subject><subject>Mutation</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Odds Ratio</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Promoter Regions, Genetic</subject><subject>Prostate</subject><subject>Prostate-specific antigen</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Risk factors</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Stem cells</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Studies</subject><subject>Transcription</subject><subject>Transcription, Genetic</subject><subject>Tumors</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0ltvFCEUAOCJsbEX9ScYorHGh1m5zQzzuNlobdKkxqoPvhAWDiPNLLMCY91_L9udtNnGRMMDBD4OHDhF8ZzgGcFMvPPdjFT0UXFEKl6XpCHicR7jmpQcs_qwOI7xGmPCORZPikMiuBCY4aPi-xl4SE6jXyo4ldzgkfPo09VijlxEKsZB52kw6MalHyiOUcM6uaXrXdqgNCDjrB0jlGmzBtSpmEKOpZXXEJ4WB1b1EZ5N_Unx9cP7L4uP5cXl2fliflHqitFUsqbV1gqr66UhCpShS82g5roFw2qzXeaixcpUQDQ23AgA3rCGWW2ZqWp2Upzu4q7D8HOEmOTK5Wv2vfIwjFE2uKkYE80_IcVNgwVvM3z5AF4PY_A5CUkprRmvWpbRqx3qVA_SeTukoPQ2opwTUQtK-e3lZn9RuRlYOT14sC7P7214u7chmwS_U6fGGOX51ef_t5ff9u2UvA5DjAGsXAe3UmEjCZbbEpK-k7mEMnwxJT8uV2Du2VQzGbyegIpa9Tbk33bxzlHMWYVbkt2bnYt5yXcQ7l_xwZF_AAu41_g</recordid><startdate>20080601</startdate><enddate>20080601</enddate><creator>Sakamoto, Hiromi</creator><creator>Yoshimura, Kimio</creator><creator>Saeki, Norihisa</creator><creator>Katai, Hitoshi</creator><creator>Shimoda, Tadakazu</creator><creator>Matsuno, Yoshihiro</creator><creator>Saito, Daizo</creator><creator>Sugimura, Haruhiko</creator><creator>Tanioka, Fumihiko</creator><creator>Kato, Shunji</creator><creator>Matsukura, Norio</creator><creator>Matsuda, Noriko</creator><creator>Nakamura, Tsuneya</creator><creator>Hyodo, Ichinosuke</creator><creator>Nishina, Tomohiro</creator><creator>Yasui, Wataru</creator><creator>Hirose, Hiroshi</creator><creator>Hayashi, Matsuhiko</creator><creator>Toshiro, Emi</creator><creator>Ohnami, Sumiko</creator><creator>Sekine, Akihiro</creator><creator>Sato, Yasunori</creator><creator>Totsuka, Hirohiko</creator><creator>Ando, Masataka</creator><creator>Takemura, Ryo</creator><creator>Takahashi, Yoriko</creator><creator>Ohdaira, Minoru</creator><creator>Aoki, Kenichi</creator><creator>Honmyo, Izumi</creator><creator>Chiku, Suenori</creator><creator>Aoyagi, Kazuhiko</creator><creator>Sasaki, Hiroki</creator><creator>Ohnami, Shumpei</creator><creator>Yanagihara, Kazuyoshi</creator><creator>Yoon, Kyong-Ah</creator><creator>Kook, Myeong-Cherl</creator><creator>Lee, Yeon-Su</creator><creator>Park, Sook Ryun</creator><creator>Kim, Chan Gyoo</creator><creator>Choi, Il Ju</creator><creator>Yoshida, Teruhiko</creator><creator>Nakamura, Yusuke</creator><creator>Hirohashi, Setsuo</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20080601</creationdate><title>Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer</title><author>Sakamoto, Hiromi ; Yoshimura, Kimio ; Saeki, Norihisa ; Katai, Hitoshi ; Shimoda, Tadakazu ; Matsuno, Yoshihiro ; Saito, Daizo ; Sugimura, Haruhiko ; Tanioka, Fumihiko ; Kato, Shunji ; Matsukura, Norio ; Matsuda, Noriko ; Nakamura, Tsuneya ; Hyodo, Ichinosuke ; Nishina, Tomohiro ; Yasui, Wataru ; Hirose, Hiroshi ; Hayashi, Matsuhiko ; Toshiro, Emi ; Ohnami, Sumiko ; Sekine, Akihiro ; Sato, Yasunori ; Totsuka, Hirohiko ; Ando, Masataka ; Takemura, Ryo ; Takahashi, Yoriko ; Ohdaira, Minoru ; Aoki, Kenichi ; Honmyo, Izumi ; Chiku, Suenori ; Aoyagi, Kazuhiko ; Sasaki, Hiroki ; Ohnami, Shumpei ; Yanagihara, Kazuyoshi ; Yoon, Kyong-Ah ; Kook, Myeong-Cherl ; Lee, Yeon-Su ; Park, Sook Ryun ; Kim, Chan Gyoo ; Choi, Il Ju ; Yoshida, Teruhiko ; Nakamura, Yusuke ; Hirohashi, Setsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-379cff8fc6bd1aead2bc3e64c9ed36d379c4890ad5e1c0d4d8ee47373fcf3d563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma, Mucinous - genetics</topic><topic>Adenocarcinoma, Mucinous - pathology</topic><topic>Agriculture</topic><topic>Alzheimer's disease</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Antigens, Neoplasm</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Carcinoma, Papillary - genetics</topic><topic>Carcinoma, Papillary - pathology</topic><topic>Carcinoma, Signet Ring Cell - genetics</topic><topic>Carcinoma, Signet Ring Cell - pathology</topic><topic>Case-Control Studies</topic><topic>Cell Proliferation</topic><topic>Cells</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Diabetes</topic><topic>Diagnosis</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Exons</topic><topic>Exons - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastric cancer</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gastrointestinal diseases</topic><topic>Gene Frequency</topic><topic>Gene Function</topic><topic>Gene polymorphism</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome, Human - genetics</topic><topic>Genomics</topic><topic>GPI-Linked Proteins</topic><topic>Haplotypes - genetics</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Intestinal Neoplasms</topic><topic>Intestine</topic><topic>Japan</topic><topic>Korea</topic><topic>Linkage Disequilibrium</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Mortality</topic><topic>Mutation</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Odds Ratio</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Promoter Regions, Genetic</topic><topic>Prostate</topic><topic>Prostate-specific antigen</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Risk factors</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Stem cells</topic><topic>Stomach cancer</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Studies</topic><topic>Transcription</topic><topic>Transcription, Genetic</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakamoto, Hiromi</creatorcontrib><creatorcontrib>Yoshimura, Kimio</creatorcontrib><creatorcontrib>Saeki, Norihisa</creatorcontrib><creatorcontrib>Katai, Hitoshi</creatorcontrib><creatorcontrib>Shimoda, Tadakazu</creatorcontrib><creatorcontrib>Matsuno, Yoshihiro</creatorcontrib><creatorcontrib>Saito, Daizo</creatorcontrib><creatorcontrib>Sugimura, Haruhiko</creatorcontrib><creatorcontrib>Tanioka, Fumihiko</creatorcontrib><creatorcontrib>Kato, Shunji</creatorcontrib><creatorcontrib>Matsukura, Norio</creatorcontrib><creatorcontrib>Matsuda, Noriko</creatorcontrib><creatorcontrib>Nakamura, Tsuneya</creatorcontrib><creatorcontrib>Hyodo, Ichinosuke</creatorcontrib><creatorcontrib>Nishina, Tomohiro</creatorcontrib><creatorcontrib>Yasui, Wataru</creatorcontrib><creatorcontrib>Hirose, Hiroshi</creatorcontrib><creatorcontrib>Hayashi, Matsuhiko</creatorcontrib><creatorcontrib>Toshiro, Emi</creatorcontrib><creatorcontrib>Ohnami, Sumiko</creatorcontrib><creatorcontrib>Sekine, Akihiro</creatorcontrib><creatorcontrib>Sato, Yasunori</creatorcontrib><creatorcontrib>Totsuka, Hirohiko</creatorcontrib><creatorcontrib>Ando, Masataka</creatorcontrib><creatorcontrib>Takemura, Ryo</creatorcontrib><creatorcontrib>Takahashi, Yoriko</creatorcontrib><creatorcontrib>Ohdaira, Minoru</creatorcontrib><creatorcontrib>Aoki, Kenichi</creatorcontrib><creatorcontrib>Honmyo, Izumi</creatorcontrib><creatorcontrib>Chiku, Suenori</creatorcontrib><creatorcontrib>Aoyagi, Kazuhiko</creatorcontrib><creatorcontrib>Sasaki, Hiroki</creatorcontrib><creatorcontrib>Ohnami, Shumpei</creatorcontrib><creatorcontrib>Yanagihara, Kazuyoshi</creatorcontrib><creatorcontrib>Yoon, Kyong-Ah</creatorcontrib><creatorcontrib>Kook, Myeong-Cherl</creatorcontrib><creatorcontrib>Lee, Yeon-Su</creatorcontrib><creatorcontrib>Park, Sook Ryun</creatorcontrib><creatorcontrib>Kim, Chan Gyoo</creatorcontrib><creatorcontrib>Choi, Il Ju</creatorcontrib><creatorcontrib>Yoshida, Teruhiko</creatorcontrib><creatorcontrib>Nakamura, Yusuke</creatorcontrib><creatorcontrib>Hirohashi, Setsuo</creatorcontrib><creatorcontrib>Study Group of Millennium Genome Project for Cancer</creatorcontrib><creatorcontrib>The Study Group of Millennium Genome Project for Cancer</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>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium 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genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakamoto, Hiromi</au><au>Yoshimura, Kimio</au><au>Saeki, Norihisa</au><au>Katai, Hitoshi</au><au>Shimoda, Tadakazu</au><au>Matsuno, Yoshihiro</au><au>Saito, Daizo</au><au>Sugimura, Haruhiko</au><au>Tanioka, Fumihiko</au><au>Kato, Shunji</au><au>Matsukura, Norio</au><au>Matsuda, Noriko</au><au>Nakamura, Tsuneya</au><au>Hyodo, Ichinosuke</au><au>Nishina, Tomohiro</au><au>Yasui, Wataru</au><au>Hirose, Hiroshi</au><au>Hayashi, Matsuhiko</au><au>Toshiro, Emi</au><au>Ohnami, Sumiko</au><au>Sekine, Akihiro</au><au>Sato, Yasunori</au><au>Totsuka, Hirohiko</au><au>Ando, Masataka</au><au>Takemura, Ryo</au><au>Takahashi, Yoriko</au><au>Ohdaira, Minoru</au><au>Aoki, Kenichi</au><au>Honmyo, Izumi</au><au>Chiku, Suenori</au><au>Aoyagi, Kazuhiko</au><au>Sasaki, Hiroki</au><au>Ohnami, Shumpei</au><au>Yanagihara, Kazuyoshi</au><au>Yoon, Kyong-Ah</au><au>Kook, Myeong-Cherl</au><au>Lee, Yeon-Su</au><au>Park, Sook Ryun</au><au>Kim, Chan Gyoo</au><au>Choi, Il Ju</au><au>Yoshida, Teruhiko</au><au>Nakamura, Yusuke</au><au>Hirohashi, Setsuo</au><aucorp>Study Group of Millennium Genome Project for Cancer</aucorp><aucorp>The Study Group of Millennium Genome Project for Cancer</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2008-06-01</date><risdate>2008</risdate><volume>40</volume><issue>6</issue><spage>730</spage><epage>740</epage><pages>730-740</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in
PSCA
(prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38–1.89,
P
= 1.11 × 10
−9
). The association was far less significant in intestinal-type gastric cancer. We found that
PSCA
is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity
in vitro
and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has
r
2
= 0.995,
D
′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33,
P
= 8.01 × 10
−11
). The polymorphism of the
PSCA
gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>18488030</pmid><doi>10.1038/ng.152</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2008-06, Vol.40 (6), p.730-740 |
| issn | 1061-4036 1546-1718 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | Adenocarcinoma - genetics Adenocarcinoma - pathology Adenocarcinoma, Mucinous - genetics Adenocarcinoma, Mucinous - pathology Agriculture Alzheimer's disease Animal Genetics and Genomics Animals Antigens, Neoplasm Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Cancer Research Carcinoma, Papillary - genetics Carcinoma, Papillary - pathology Carcinoma, Signet Ring Cell - genetics Carcinoma, Signet Ring Cell - pathology Case-Control Studies Cell Proliferation Cells CHO Cells Cricetinae Cricetulus Diabetes Diagnosis Epithelial cells Epithelium Exons Exons - genetics Fundamental and applied biological sciences. Psychology Gastric cancer Gastroenterology. Liver. Pancreas. Abdomen Gastrointestinal diseases Gene Frequency Gene Function Gene polymorphism Genetic aspects Genetic diversity Genetic Predisposition to Disease Genetic Variation Genetics of eukaryotes. Biological and molecular evolution Genome, Human - genetics Genomics GPI-Linked Proteins Haplotypes - genetics Health aspects Human Genetics Humans Immunoenzyme Techniques Intestinal Neoplasms Intestine Japan Korea Linkage Disequilibrium Medical sciences Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Mortality Mutation Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Odds Ratio Physiological aspects Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic Prostate Prostate-specific antigen Reverse Transcriptase Polymerase Chain Reaction Risk factors RNA, Messenger - genetics RNA, Messenger - metabolism Single nucleotide polymorphisms Single-nucleotide polymorphism Stem cells Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - pathology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Studies Transcription Transcription, Genetic Tumors |
| title | Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer |
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