Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis
Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis...
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| creator | He, Jing Xi, Bo Ruiter, Rikje Shi, Ting-Yan Zhu, Mei-Ling Wang, Meng-Yun Li, Qiao-Xin Zhou, Xiao-Yan Qiu, Li-Xin Wei, Qing-Yi |
| description | Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.
We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.
The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.
Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies. |
| doi_str_mv | 10.1371/journal.pone.0075135 |
| format | Article |
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We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.
The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.
Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0075135</identifier><identifier>PMID: 24146750</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Bibliographic literature ; Breast cancer ; Cancer ; Case-Control Studies ; Continental Population Groups ; Databases, Bibliographic ; Disease susceptibility ; Epidemiology ; Gene expression ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease ; Genotypes ; HapMap Project ; Health risk assessment ; Health risks ; Humans ; Leptin ; Leptin - genetics ; Male ; Maternal & child health ; Meta-analysis ; Metabolism ; Minority & ethnic groups ; Models, Genetic ; Neoplasms - ethnology ; Neoplasms - genetics ; Oncology ; Polymorphism, Single Nucleotide ; Prostate cancer ; Prostatic Neoplasms - ethnology ; Prostatic Neoplasms - genetics ; Proteins ; Public health ; Receptors, Leptin - genetics ; Risk ; RNA ; RNA, Messenger - genetics ; Single-nucleotide polymorphism ; Statistical analysis ; Statistics ; Studies ; Type 2 diabetes</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e75135-e75135</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 He et al 2013 He et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-228dcde21c9a2b2dde351c4dd4bc83158e158ebd40c69e9aa1155795da4974ba3</citedby><cites>FETCH-LOGICAL-c692t-228dcde21c9a2b2dde351c4dd4bc83158e158ebd40c69e9aa1155795da4974ba3</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/PMC3798550/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798550/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24146750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Huang, Qingyang</contributor><creatorcontrib>He, Jing</creatorcontrib><creatorcontrib>Xi, Bo</creatorcontrib><creatorcontrib>Ruiter, Rikje</creatorcontrib><creatorcontrib>Shi, Ting-Yan</creatorcontrib><creatorcontrib>Zhu, Mei-Ling</creatorcontrib><creatorcontrib>Wang, Meng-Yun</creatorcontrib><creatorcontrib>Li, Qiao-Xin</creatorcontrib><creatorcontrib>Zhou, Xiao-Yan</creatorcontrib><creatorcontrib>Qiu, Li-Xin</creatorcontrib><creatorcontrib>Wei, Qing-Yi</creatorcontrib><title>Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.
We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.
The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.
Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.</description><subject>Analysis</subject><subject>Bibliographic literature</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>Continental Population Groups</subject><subject>Databases, Bibliographic</subject><subject>Disease susceptibility</subject><subject>Epidemiology</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotypes</subject><subject>HapMap Project</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Humans</subject><subject>Leptin</subject><subject>Leptin - genetics</subject><subject>Male</subject><subject>Maternal & child health</subject><subject>Meta-analysis</subject><subject>Metabolism</subject><subject>Minority & ethnic groups</subject><subject>Models, Genetic</subject><subject>Neoplasms - ethnology</subject><subject>Neoplasms - genetics</subject><subject>Oncology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - ethnology</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Proteins</subject><subject>Public health</subject><subject>Receptors, Leptin - genetics</subject><subject>Risk</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>Statistics</subject><subject>Studies</subject><subject>Type 2 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of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis</title><author>He, Jing ; Xi, Bo ; Ruiter, Rikje ; Shi, Ting-Yan ; Zhu, Mei-Ling ; Wang, Meng-Yun ; Li, Qiao-Xin ; Zhou, Xiao-Yan ; Qiu, Li-Xin ; Wei, Qing-Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-228dcde21c9a2b2dde351c4dd4bc83158e158ebd40c69e9aa1155795da4974ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Bibliographic literature</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Case-Control Studies</topic><topic>Continental Population Groups</topic><topic>Databases, Bibliographic</topic><topic>Disease susceptibility</topic><topic>Epidemiology</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotypes</topic><topic>HapMap Project</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Humans</topic><topic>Leptin</topic><topic>Leptin - genetics</topic><topic>Male</topic><topic>Maternal & child health</topic><topic>Meta-analysis</topic><topic>Metabolism</topic><topic>Minority & ethnic groups</topic><topic>Models, Genetic</topic><topic>Neoplasms - ethnology</topic><topic>Neoplasms - genetics</topic><topic>Oncology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - ethnology</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Proteins</topic><topic>Public health</topic><topic>Receptors, Leptin - genetics</topic><topic>Risk</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>Statistics</topic><topic>Studies</topic><topic>Type 2 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Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Jing</au><au>Xi, Bo</au><au>Ruiter, Rikje</au><au>Shi, Ting-Yan</au><au>Zhu, Mei-Ling</au><au>Wang, Meng-Yun</au><au>Li, Qiao-Xin</au><au>Zhou, Xiao-Yan</au><au>Qiu, Li-Xin</au><au>Wei, Qing-Yi</au><au>Huang, Qingyang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-17</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e75135</spage><epage>e75135</epage><pages>e75135-e75135</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.
We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.
The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.
Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24146750</pmid><doi>10.1371/journal.pone.0075135</doi><tpages>e75135</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1442651575 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Bibliographic literature Breast cancer Cancer Case-Control Studies Continental Population Groups Databases, Bibliographic Disease susceptibility Epidemiology Gene expression Genetic aspects Genetic diversity Genetic Predisposition to Disease Genotypes HapMap Project Health risk assessment Health risks Humans Leptin Leptin - genetics Male Maternal & child health Meta-analysis Metabolism Minority & ethnic groups Models, Genetic Neoplasms - ethnology Neoplasms - genetics Oncology Polymorphism, Single Nucleotide Prostate cancer Prostatic Neoplasms - ethnology Prostatic Neoplasms - genetics Proteins Public health Receptors, Leptin - genetics Risk RNA RNA, Messenger - genetics Single-nucleotide polymorphism Statistical analysis Statistics Studies Type 2 diabetes |
| title | Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T10%3A41%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20of%20LEP%20G2548A%20and%20LEPR%20Q223R%20polymorphisms%20with%20cancer%20susceptibility:%20evidence%20from%20a%20meta-analysis&rft.jtitle=PloS%20one&rft.au=He,%20Jing&rft.date=2013-10-17&rft.volume=8&rft.issue=10&rft.spage=e75135&rft.epage=e75135&rft.pages=e75135-e75135&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0075135&rft_dat=%3Cgale_plos_%3EA478233246%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1442651575&rft_id=info:pmid/24146750&rft_galeid=A478233246&rft_doaj_id=oai_doaj_org_article_836d73f2e60f4dcb9a922d3c35cd34e1&rfr_iscdi=true |