Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese
Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic va...
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| Veröffentlicht in: | American journal of human genetics 2012-11, Vol.91 (5), p.928-934 |
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| creator | Jin, Guangfu Ma, Hongxia Wu, Chen Dai, Juncheng Zhang, Ruyang Shi, Yongyong Lu, Jiachun Miao, Xiaoping Wang, Meilin Zhou, Yifeng Chen, Jiaping Li, Huizhang Pan, Shandong Chu, Minjie Lu, Feng Yu, Dianke Jiang, Yue Dong, Jing Hu, Lingmin Chen, Yijiang Xu, Lin Shu, Yongqian Pan, Shiyang Tan, Wen Zhou, Baosen Lu, Daru Wu, Tangchun Zhang, Zhengdong Chen, Feng Wang, Xinru Hu, Zhibin Lin, Dongxin Shen, Hongbing |
| description | Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers. |
| doi_str_mv | 10.1016/j.ajhg.2012.09.009 |
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We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1016/j.ajhg.2012.09.009</identifier><identifier>PMID: 23103227</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Cambridge, MA: Cell Press</publisher><subject>Aged ; Asian Continental Ancestry Group - genetics ; Biological and medical sciences ; Cancer ; Carcinoma, Squamous Cell - epidemiology ; Carcinoma, Squamous Cell - genetics ; China - epidemiology ; Chromosomes, Human, Pair 6 ; Chromosomes, Human, Pair 7 ; Esophageal Neoplasms - epidemiology ; Esophageal Neoplasms - genetics ; Female ; Fundamental and applied biological sciences. Psychology ; Genes ; Genetic Predisposition to Disease ; Genetic Variation ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; Genomes ; Humans ; Lung Neoplasms - epidemiology ; Lung Neoplasms - genetics ; Male ; Medical genetics ; Medical sciences ; Middle Aged ; Molecular and cellular biology ; Neoplasms, Multiple Primary - epidemiology ; Neoplasms, Multiple Primary - genetics ; Risk ; Risk assessment ; Stomach Neoplasms - epidemiology ; Stomach Neoplasms - genetics ; Tumors</subject><ispartof>American journal of human genetics, 2012-11, Vol.91 (5), p.928-934</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Cell Press Nov 2, 2012</rights><rights>2012 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. 2012 The American Society of Human Genetics</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-a1f15da52c76d016ebf3bde7a1ade49e9f87dc434e10ba1b375bc138be615bcf3</citedby><cites>FETCH-LOGICAL-c493t-a1f15da52c76d016ebf3bde7a1ade49e9f87dc434e10ba1b375bc138be615bcf3</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/PMC3487121/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487121/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26584315$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23103227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Guangfu</creatorcontrib><creatorcontrib>Ma, Hongxia</creatorcontrib><creatorcontrib>Wu, Chen</creatorcontrib><creatorcontrib>Dai, Juncheng</creatorcontrib><creatorcontrib>Zhang, Ruyang</creatorcontrib><creatorcontrib>Shi, Yongyong</creatorcontrib><creatorcontrib>Lu, Jiachun</creatorcontrib><creatorcontrib>Miao, Xiaoping</creatorcontrib><creatorcontrib>Wang, Meilin</creatorcontrib><creatorcontrib>Zhou, Yifeng</creatorcontrib><creatorcontrib>Chen, Jiaping</creatorcontrib><creatorcontrib>Li, Huizhang</creatorcontrib><creatorcontrib>Pan, Shandong</creatorcontrib><creatorcontrib>Chu, Minjie</creatorcontrib><creatorcontrib>Lu, Feng</creatorcontrib><creatorcontrib>Yu, Dianke</creatorcontrib><creatorcontrib>Jiang, Yue</creatorcontrib><creatorcontrib>Dong, Jing</creatorcontrib><creatorcontrib>Hu, Lingmin</creatorcontrib><creatorcontrib>Chen, Yijiang</creatorcontrib><creatorcontrib>Xu, Lin</creatorcontrib><creatorcontrib>Shu, Yongqian</creatorcontrib><creatorcontrib>Pan, Shiyang</creatorcontrib><creatorcontrib>Tan, Wen</creatorcontrib><creatorcontrib>Zhou, Baosen</creatorcontrib><creatorcontrib>Lu, Daru</creatorcontrib><creatorcontrib>Wu, Tangchun</creatorcontrib><creatorcontrib>Zhang, Zhengdong</creatorcontrib><creatorcontrib>Chen, Feng</creatorcontrib><creatorcontrib>Wang, Xinru</creatorcontrib><creatorcontrib>Hu, Zhibin</creatorcontrib><creatorcontrib>Lin, Dongxin</creatorcontrib><creatorcontrib>Shen, Hongbing</creatorcontrib><title>Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.</description><subject>Aged</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - epidemiology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>China - epidemiology</subject><subject>Chromosomes, Human, Pair 6</subject><subject>Chromosomes, Human, Pair 7</subject><subject>Esophageal Neoplasms - epidemiology</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humans</subject><subject>Lung Neoplasms - epidemiology</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Neoplasms, Multiple Primary - epidemiology</subject><subject>Neoplasms, Multiple Primary - genetics</subject><subject>Risk</subject><subject>Risk assessment</subject><subject>Stomach Neoplasms - epidemiology</subject><subject>Stomach Neoplasms - genetics</subject><subject>Tumors</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkV-r1DAQxYMo3nX1C_ggARF8ac0kbdO-CMui9wpXBFFfwzSd3k3tpjVpFb-9We56_fOUgfzmzJw5jD0FkYOA6tWQ43C4yaUAmYsmF6K5xzZQKp1VlSjvs40QQmaNbPQFexTjIARALdRDdiEVCCWl3jC8JE-Ls_wLBod-iRwXXs0ScuDoO65nKHPFd4H4LsbJOlyo4z_ccuAfXfzKp56_X8fFzSPxPXpLIXLn-RV6vj84T5Eeswc9jpGenN8t-_z2zaf9VXb94fLdfned2aJRS4bQQ9lhKa2uuuSO2l61HWkE7KhoqOlr3dlCFQSiRWiVLlsLqm6pglT1aste3-rOa3ukzpJfAo5mDu6I4aeZ0Jl_f7w7mJvpu1FFrUFCEnh5FgjTt5XiYo4uWhpH9DSt0YDUUkOj04W37Pl_6DCtwSd7iaorXdZVWSdK3lI2TDEG6u-WAWFOCZrBnBI0pwSNaExKMDU9-9vGXcvvyBLw4gxgtDj2IV3dxT9cmlyotOMvRNqj7w</recordid><startdate>20121102</startdate><enddate>20121102</enddate><creator>Jin, Guangfu</creator><creator>Ma, Hongxia</creator><creator>Wu, Chen</creator><creator>Dai, Juncheng</creator><creator>Zhang, Ruyang</creator><creator>Shi, Yongyong</creator><creator>Lu, Jiachun</creator><creator>Miao, Xiaoping</creator><creator>Wang, Meilin</creator><creator>Zhou, Yifeng</creator><creator>Chen, Jiaping</creator><creator>Li, Huizhang</creator><creator>Pan, Shandong</creator><creator>Chu, Minjie</creator><creator>Lu, Feng</creator><creator>Yu, Dianke</creator><creator>Jiang, Yue</creator><creator>Dong, Jing</creator><creator>Hu, Lingmin</creator><creator>Chen, Yijiang</creator><creator>Xu, Lin</creator><creator>Shu, Yongqian</creator><creator>Pan, Shiyang</creator><creator>Tan, Wen</creator><creator>Zhou, Baosen</creator><creator>Lu, Daru</creator><creator>Wu, Tangchun</creator><creator>Zhang, Zhengdong</creator><creator>Chen, Feng</creator><creator>Wang, Xinru</creator><creator>Hu, Zhibin</creator><creator>Lin, Dongxin</creator><creator>Shen, Hongbing</creator><general>Cell Press</general><general>Elsevier</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>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20121102</creationdate><title>Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese</title><author>Jin, Guangfu ; Ma, Hongxia ; Wu, Chen ; Dai, Juncheng ; Zhang, Ruyang ; Shi, Yongyong ; Lu, Jiachun ; Miao, Xiaoping ; Wang, Meilin ; Zhou, Yifeng ; Chen, Jiaping ; Li, Huizhang ; Pan, Shandong ; Chu, Minjie ; Lu, Feng ; Yu, Dianke ; Jiang, Yue ; Dong, Jing ; Hu, Lingmin ; Chen, Yijiang ; Xu, Lin ; Shu, Yongqian ; Pan, Shiyang ; Tan, Wen ; Zhou, Baosen ; Lu, Daru ; Wu, Tangchun ; Zhang, Zhengdong ; Chen, Feng ; Wang, Xinru ; Hu, Zhibin ; Lin, Dongxin ; Shen, Hongbing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-a1f15da52c76d016ebf3bde7a1ade49e9f87dc434e10ba1b375bc138be615bcf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - epidemiology</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>China - epidemiology</topic><topic>Chromosomes, Human, Pair 6</topic><topic>Chromosomes, Human, Pair 7</topic><topic>Esophageal Neoplasms - epidemiology</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genetics of eukaryotes. 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We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.</abstract><cop>Cambridge, MA</cop><pub>Cell Press</pub><pmid>23103227</pmid><doi>10.1016/j.ajhg.2012.09.009</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of human genetics, 2012-11, Vol.91 (5), p.928-934 |
| issn | 0002-9297 1537-6605 |
| language | eng |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Aged Asian Continental Ancestry Group - genetics Biological and medical sciences Cancer Carcinoma, Squamous Cell - epidemiology Carcinoma, Squamous Cell - genetics China - epidemiology Chromosomes, Human, Pair 6 Chromosomes, Human, Pair 7 Esophageal Neoplasms - epidemiology Esophageal Neoplasms - genetics Female Fundamental and applied biological sciences. Psychology Genes Genetic Predisposition to Disease Genetic Variation Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genomes Humans Lung Neoplasms - epidemiology Lung Neoplasms - genetics Male Medical genetics Medical sciences Middle Aged Molecular and cellular biology Neoplasms, Multiple Primary - epidemiology Neoplasms, Multiple Primary - genetics Risk Risk assessment Stomach Neoplasms - epidemiology Stomach Neoplasms - genetics Tumors |
| title | Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T00%3A07%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Variants%20at%206p21.1%20and%207p15.3%20Are%20Associated%20with%20Risk%20of%20Multiple%20Cancers%20in%20Han%20Chinese&rft.jtitle=American%20journal%20of%20human%20genetics&rft.au=Jin,%20Guangfu&rft.date=2012-11-02&rft.volume=91&rft.issue=5&rft.spage=928&rft.epage=934&rft.pages=928-934&rft.issn=0002-9297&rft.eissn=1537-6605&rft.coden=AJHGAG&rft_id=info:doi/10.1016/j.ajhg.2012.09.009&rft_dat=%3Cproquest_pubme%3E2889578251%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1286758658&rft_id=info:pmid/23103227&rfr_iscdi=true |