Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length
Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a T...
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| Veröffentlicht in: | International journal of cancer 2015-03, Vol.136 (5), p.E351-E358 |
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| creator | Campa, Daniele Martino, Alessandro Varkonyi, Judit Lesueur, Fabienne Jamroziak, Krzysztof Landi, Stefano Jurczyszyn, Artur Marques, Herlander Andersen, Vibeke Jurado, Manuel Brenner, Hermann Petrini, Mario Vogel, Ulla García‐Sanz, Ramón Buda, Gabriele Gemignani, Federica Ríos, Rafael Vangsted, Annette Juul Dumontet, Charles Martínez‐López, Joaquín Moreno, María José Stępień, Anna Wątek, Marzena Moreno, Victor Dieffenbach, Aida Karina Rossi, Anna Maria Butterbach, Katja Jacobsen, Svend E. Hove Goldschmidt, Hartmut Sainz, Juan Hillengass, Jens Orciuolo, Enrico Dudziński, Marek Weinhold, Niels Reis, Rui Manuel Canzian, Federico |
| description | Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72–0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy‐free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63–2.24; ptrend = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.
What's new?
A critical element of cancer cell immortality is the maintenance of telomere length, a process that is influenced in part by genetic variations in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). At the TERT locus in particular, certain variations are linked with either increased or decreased risk of a variety of malignancies. In the present study, a variant of TERT known as rs2242652 was associated with reduced risk of multiple myeloma. Compared with controls, patients with multiple myeloma were found to possess longer telomeres, suggesting an association between increased telomere length and increased multiple myeloma risk. |
| doi_str_mv | 10.1002/ijc.29101 |
| format | Article |
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What's new?
A critical element of cancer cell immortality is the maintenance of telomere length, a process that is influenced in part by genetic variations in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). At the TERT locus in particular, certain variations are linked with either increased or decreased risk of a variety of malignancies. In the present study, a variant of TERT known as rs2242652 was associated with reduced risk of multiple myeloma. Compared with controls, patients with multiple myeloma were found to possess longer telomeres, suggesting an association between increased telomere length and increased multiple myeloma risk.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.29101</identifier><identifier>PMID: 25066524</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Aged ; Bone cancer ; Bone marrow ; Cancer ; Case-Control Studies ; Cohort Studies ; Computational Biology ; Female ; Follow-Up Studies ; Genes ; Genetic Predisposition to Disease ; Germany - epidemiology ; Humans ; Leukocytes ; Male ; Medical research ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - epidemiology ; Multiple Myeloma - genetics ; Polymorphism, Genetic - genetics ; polymorphisms ; Prognosis ; Risk Factors ; susceptibility ; Telomerase ; Telomerase - genetics ; Telomere Homeostasis - genetics ; telomere length</subject><ispartof>International journal of cancer, 2015-03, Vol.136 (5), p.E351-E358</ispartof><rights>2014 UICC</rights><rights>2014 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5161-1ad63175931951fbb33643d38f4a7cf903cb0a0c96b8d6fd5ab77e554b220ea3</citedby><cites>FETCH-LOGICAL-c5161-1ad63175931951fbb33643d38f4a7cf903cb0a0c96b8d6fd5ab77e554b220ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.29101$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.29101$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25066524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Campa, Daniele</creatorcontrib><creatorcontrib>Martino, Alessandro</creatorcontrib><creatorcontrib>Varkonyi, Judit</creatorcontrib><creatorcontrib>Lesueur, Fabienne</creatorcontrib><creatorcontrib>Jamroziak, Krzysztof</creatorcontrib><creatorcontrib>Landi, Stefano</creatorcontrib><creatorcontrib>Jurczyszyn, Artur</creatorcontrib><creatorcontrib>Marques, Herlander</creatorcontrib><creatorcontrib>Andersen, Vibeke</creatorcontrib><creatorcontrib>Jurado, Manuel</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Petrini, Mario</creatorcontrib><creatorcontrib>Vogel, Ulla</creatorcontrib><creatorcontrib>García‐Sanz, Ramón</creatorcontrib><creatorcontrib>Buda, Gabriele</creatorcontrib><creatorcontrib>Gemignani, Federica</creatorcontrib><creatorcontrib>Ríos, Rafael</creatorcontrib><creatorcontrib>Vangsted, Annette Juul</creatorcontrib><creatorcontrib>Dumontet, Charles</creatorcontrib><creatorcontrib>Martínez‐López, Joaquín</creatorcontrib><creatorcontrib>Moreno, María José</creatorcontrib><creatorcontrib>Stępień, Anna</creatorcontrib><creatorcontrib>Wątek, Marzena</creatorcontrib><creatorcontrib>Moreno, Victor</creatorcontrib><creatorcontrib>Dieffenbach, Aida Karina</creatorcontrib><creatorcontrib>Rossi, Anna Maria</creatorcontrib><creatorcontrib>Butterbach, Katja</creatorcontrib><creatorcontrib>Jacobsen, Svend E. Hove</creatorcontrib><creatorcontrib>Goldschmidt, Hartmut</creatorcontrib><creatorcontrib>Sainz, Juan</creatorcontrib><creatorcontrib>Hillengass, Jens</creatorcontrib><creatorcontrib>Orciuolo, Enrico</creatorcontrib><creatorcontrib>Dudziński, Marek</creatorcontrib><creatorcontrib>Weinhold, Niels</creatorcontrib><creatorcontrib>Reis, Rui Manuel</creatorcontrib><creatorcontrib>Canzian, Federico</creatorcontrib><title>Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72–0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy‐free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63–2.24; ptrend = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.
What's new?
A critical element of cancer cell immortality is the maintenance of telomere length, a process that is influenced in part by genetic variations in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). At the TERT locus in particular, certain variations are linked with either increased or decreased risk of a variety of malignancies. In the present study, a variant of TERT known as rs2242652 was associated with reduced risk of multiple myeloma. Compared with controls, patients with multiple myeloma were found to possess longer telomeres, suggesting an association between increased telomere length and increased multiple myeloma risk.</description><subject>Aged</subject><subject>Bone cancer</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>Computational Biology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Germany - epidemiology</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - epidemiology</subject><subject>Multiple Myeloma - genetics</subject><subject>Polymorphism, Genetic - genetics</subject><subject>polymorphisms</subject><subject>Prognosis</subject><subject>Risk Factors</subject><subject>susceptibility</subject><subject>Telomerase</subject><subject>Telomerase - genetics</subject><subject>Telomere Homeostasis - genetics</subject><subject>telomere length</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1LxDAQBuAgiq4fB_-ABLzooW4maRJ7lMVPFgTxXtJ26mZNm9q0yP57s656EMRTYPLMC8NLyDGwC2CMT-2yvOAZMNgiE2CZThgHuU0m8Y8lGoTaI_shLBkDkCzdJXtcMqUkTycEn2x4pb6mzegG2zmkzQqdbwy1gZoQfGnNgBV9t8OCdt6tGt93Cxua8DmyLR3WHHsTkL5gi3Grrb6HSB22L8PikOzUxgU8-noPyPPN9fPsLpk_3t7PruZJKUFBAqZSArTMBGQS6qIQQqWiEpd1anRZZ0yUBTOszFRxWam6kqbQGqVMC84ZGnFAzjaxXe_fRgxD3thQonOmRT-GHJRMlQYVQ_-nQkulgOtIT3_RpR_7Nt6xVgoUT9MsqvONKnsfQo913vW2Mf0qB5avW8pjS_lnS9GefCWORYPVj_yuJYLpBrxbh6u_k_L7h9km8gPQKJt7</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Campa, Daniele</creator><creator>Martino, Alessandro</creator><creator>Varkonyi, Judit</creator><creator>Lesueur, Fabienne</creator><creator>Jamroziak, Krzysztof</creator><creator>Landi, Stefano</creator><creator>Jurczyszyn, Artur</creator><creator>Marques, Herlander</creator><creator>Andersen, Vibeke</creator><creator>Jurado, Manuel</creator><creator>Brenner, Hermann</creator><creator>Petrini, Mario</creator><creator>Vogel, Ulla</creator><creator>García‐Sanz, Ramón</creator><creator>Buda, Gabriele</creator><creator>Gemignani, Federica</creator><creator>Ríos, Rafael</creator><creator>Vangsted, Annette Juul</creator><creator>Dumontet, Charles</creator><creator>Martínez‐López, Joaquín</creator><creator>Moreno, María José</creator><creator>Stępień, Anna</creator><creator>Wątek, Marzena</creator><creator>Moreno, Victor</creator><creator>Dieffenbach, Aida Karina</creator><creator>Rossi, Anna Maria</creator><creator>Butterbach, Katja</creator><creator>Jacobsen, Svend E. 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Hove</au><au>Goldschmidt, Hartmut</au><au>Sainz, Juan</au><au>Hillengass, Jens</au><au>Orciuolo, Enrico</au><au>Dudziński, Marek</au><au>Weinhold, Niels</au><au>Reis, Rui Manuel</au><au>Canzian, Federico</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>136</volume><issue>5</issue><spage>E351</spage><epage>E358</epage><pages>E351-E358</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72–0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy‐free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63–2.24; ptrend = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.
What's new?
A critical element of cancer cell immortality is the maintenance of telomere length, a process that is influenced in part by genetic variations in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). At the TERT locus in particular, certain variations are linked with either increased or decreased risk of a variety of malignancies. In the present study, a variant of TERT known as rs2242652 was associated with reduced risk of multiple myeloma. Compared with controls, patients with multiple myeloma were found to possess longer telomeres, suggesting an association between increased telomere length and increased multiple myeloma risk.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>25066524</pmid><doi>10.1002/ijc.29101</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | International journal of cancer, 2015-03, Vol.136 (5), p.E351-E358 |
| issn | 0020-7136 1097-0215 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1654671664 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library |
| subjects | Aged Bone cancer Bone marrow Cancer Case-Control Studies Cohort Studies Computational Biology Female Follow-Up Studies Genes Genetic Predisposition to Disease Germany - epidemiology Humans Leukocytes Male Medical research Middle Aged Multiple myeloma Multiple Myeloma - epidemiology Multiple Myeloma - genetics Polymorphism, Genetic - genetics polymorphisms Prognosis Risk Factors susceptibility Telomerase Telomerase - genetics Telomere Homeostasis - genetics telomere length |
| title | Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-05T01%3A18%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Risk%20of%20multiple%20myeloma%20is%20associated%20with%20polymorphisms%20within%20telomerase%20genes%20and%20telomere%20length&rft.jtitle=International%20journal%20of%20cancer&rft.au=Campa,%20Daniele&rft.date=2015-03-01&rft.volume=136&rft.issue=5&rft.spage=E351&rft.epage=E358&rft.pages=E351-E358&rft.issn=0020-7136&rft.eissn=1097-0215&rft_id=info:doi/10.1002/ijc.29101&rft_dat=%3Cproquest_cross%3E1637566127%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1636162449&rft_id=info:pmid/25066524&rfr_iscdi=true |