Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population
Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-Hodgkin’s lymphoma. In a retrospective analysis of 185...
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| creator | Kurzwelly, Delia Knop, Stefan Guenther, Markus Loeffler, Juergen Korfel, Agnieszka Thiel, Eckhard Hebart, Holger Simon, Matthias Weller, Michael Linnebank, Michael Herrlinger, Ulrich |
| description | Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-Hodgkin’s lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms affecting methionine metabolism for potential association with the development of PCNSL. We observed underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine
S
-methyltransferase (
MTR
) c.2756A > G (D919G) missense polymorphism among PCNSL patients (
P
= 0.045; odds ratio (OR) = 0.65; 0.43–0.99). Furthermore, for the methylenetetrahydrofolate reductase (
MTHFR
) c.1298A > C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (
P
= 0.026; OR = 1.57; 1.05–2.34). There were no associations of the other polymorphisms investigated (
MTHFR
c.677C > T, transcobalamin 2 (
Tc2
) c.776C > G, cystathionin beta-synthase (
CBS
) c.844_855ins68, reduced folate carrier-1 (
RFC
-
1
) c.80G > A, thymidylate synthase (
TYMS
) 28-bp repeat, and dihydrofolate reductase (
DHFR
) c.594 + 59del19 bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL. |
| doi_str_mv | 10.1007/s11060-010-0154-4 |
| format | Article |
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S
-methyltransferase (
MTR
) c.2756A > G (D919G) missense polymorphism among PCNSL patients (
P
= 0.045; odds ratio (OR) = 0.65; 0.43–0.99). Furthermore, for the methylenetetrahydrofolate reductase (
MTHFR
) c.1298A > C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (
P
= 0.026; OR = 1.57; 1.05–2.34). There were no associations of the other polymorphisms investigated (
MTHFR
c.677C > T, transcobalamin 2 (
Tc2
) c.776C > G, cystathionin beta-synthase (
CBS
) c.844_855ins68, reduced folate carrier-1 (
RFC
-
1
) c.80G > A, thymidylate synthase (
TYMS
) 28-bp repeat, and dihydrofolate reductase (
DHFR
) c.594 + 59del19 bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-010-0154-4</identifier><identifier>PMID: 20237949</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Central Nervous System Neoplasms - epidemiology ; Central Nervous System Neoplasms - genetics ; Central Nervous System Neoplasms - metabolism ; Clinical Study - Patient Study ; European Continental Ancestry Group - genetics ; Female ; Folic Acid - genetics ; Folic Acid - metabolism ; Genetic Predisposition to Disease - epidemiology ; Genetic Predisposition to Disease - genetics ; Genotype ; Germany - epidemiology ; Humans ; Incidence ; Lymphoma - epidemiology ; Lymphoma - genetics ; Lymphoma - metabolism ; Male ; Medicine ; Medicine & Public Health ; Methionine - genetics ; Methionine - metabolism ; Middle Aged ; Neurology ; Oncology ; Polymorphism, Single Nucleotide</subject><ispartof>Journal of neuro-oncology, 2010-11, Vol.100 (2), p.187-192</ispartof><rights>Springer Science+Business Media, LLC. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-96d2e181df5572a5f163880834344f4b65c53bd6660f1c033a9f4632c7c48df33</citedby><cites>FETCH-LOGICAL-c445t-96d2e181df5572a5f163880834344f4b65c53bd6660f1c033a9f4632c7c48df33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11060-010-0154-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11060-010-0154-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20237949$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kurzwelly, Delia</creatorcontrib><creatorcontrib>Knop, Stefan</creatorcontrib><creatorcontrib>Guenther, Markus</creatorcontrib><creatorcontrib>Loeffler, Juergen</creatorcontrib><creatorcontrib>Korfel, Agnieszka</creatorcontrib><creatorcontrib>Thiel, Eckhard</creatorcontrib><creatorcontrib>Hebart, Holger</creatorcontrib><creatorcontrib>Simon, Matthias</creatorcontrib><creatorcontrib>Weller, Michael</creatorcontrib><creatorcontrib>Linnebank, Michael</creatorcontrib><creatorcontrib>Herrlinger, Ulrich</creatorcontrib><title>Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population</title><title>Journal of neuro-oncology</title><addtitle>J Neurooncol</addtitle><addtitle>J Neurooncol</addtitle><description>Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-Hodgkin’s lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms affecting methionine metabolism for potential association with the development of PCNSL. We observed underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine
S
-methyltransferase (
MTR
) c.2756A > G (D919G) missense polymorphism among PCNSL patients (
P
= 0.045; odds ratio (OR) = 0.65; 0.43–0.99). Furthermore, for the methylenetetrahydrofolate reductase (
MTHFR
) c.1298A > C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (
P
= 0.026; OR = 1.57; 1.05–2.34). There were no associations of the other polymorphisms investigated (
MTHFR
c.677C > T, transcobalamin 2 (
Tc2
) c.776C > G, cystathionin beta-synthase (
CBS
) c.844_855ins68, reduced folate carrier-1 (
RFC
-
1
) c.80G > A, thymidylate synthase (
TYMS
) 28-bp repeat, and dihydrofolate reductase (
DHFR
) c.594 + 59del19 bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Central Nervous System Neoplasms - epidemiology</subject><subject>Central Nervous System Neoplasms - genetics</subject><subject>Central Nervous System Neoplasms - metabolism</subject><subject>Clinical Study - Patient Study</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>Folic Acid - genetics</subject><subject>Folic Acid - metabolism</subject><subject>Genetic Predisposition to Disease - epidemiology</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotype</subject><subject>Germany - epidemiology</subject><subject>Humans</subject><subject>Incidence</subject><subject>Lymphoma - epidemiology</subject><subject>Lymphoma - genetics</subject><subject>Lymphoma - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methionine - genetics</subject><subject>Methionine - metabolism</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Oncology</subject><subject>Polymorphism, Single Nucleotide</subject><issn>0167-594X</issn><issn>1573-7373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkU2LFDEQhoMo7rj6A7xI8OKptarz1X2UYR2FQQUVvIVMOlmzdCdt0i347007q4IgHkIK6qmnSF5CHiM8RwD1oiCChAZwO4I3_A7ZoVCsUUyxu2QHKFUjev75gjwo5QYAuGJ4n1y00DLV835Hrg8uuiVY-s3kYOJSaPLUp9Esjpo40MktX0KKIbqtNKc0hjL97Lzfv_1wpCHaMLhoXa2ooQeXJxPpbJbg4kLnNK9VVQUPyT1vxuIe3d6X5NOrq4_7183x3eHN_uWxsZyLpenl0DrscPBCqNYIj5J1HXSMM849P0lhBTsNUkrwaIEx03suWWuV5d3gGbskz87eOaevqyuLnkKxbhxNdGktupPAesT6P_8loeOS9wIr-fQv8iatOdZnVEgJJVq-LcYzZHMqJTuv5xwmk79rBL2lpc9p6ZqW3tLSvM48uRWvp8kNvyd-xVOB9gyU2orXLv_Z_G_rD6vQnc8</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Kurzwelly, Delia</creator><creator>Knop, Stefan</creator><creator>Guenther, Markus</creator><creator>Loeffler, Juergen</creator><creator>Korfel, Agnieszka</creator><creator>Thiel, Eckhard</creator><creator>Hebart, Holger</creator><creator>Simon, Matthias</creator><creator>Weller, Michael</creator><creator>Linnebank, Michael</creator><creator>Herrlinger, Ulrich</creator><general>Springer US</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20101101</creationdate><title>Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population</title><author>Kurzwelly, Delia ; Knop, Stefan ; Guenther, Markus ; Loeffler, Juergen ; Korfel, Agnieszka ; Thiel, Eckhard ; Hebart, Holger ; Simon, Matthias ; Weller, Michael ; Linnebank, Michael ; Herrlinger, Ulrich</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-96d2e181df5572a5f163880834344f4b65c53bd6660f1c033a9f4632c7c48df33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Central Nervous System Neoplasms - epidemiology</topic><topic>Central Nervous System Neoplasms - genetics</topic><topic>Central Nervous System Neoplasms - metabolism</topic><topic>Clinical Study - Patient Study</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>Folic Acid - genetics</topic><topic>Folic Acid - metabolism</topic><topic>Genetic Predisposition to Disease - epidemiology</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>Germany - epidemiology</topic><topic>Humans</topic><topic>Incidence</topic><topic>Lymphoma - epidemiology</topic><topic>Lymphoma - genetics</topic><topic>Lymphoma - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methionine - genetics</topic><topic>Methionine - metabolism</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Oncology</topic><topic>Polymorphism, Single Nucleotide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kurzwelly, Delia</creatorcontrib><creatorcontrib>Knop, Stefan</creatorcontrib><creatorcontrib>Guenther, Markus</creatorcontrib><creatorcontrib>Loeffler, Juergen</creatorcontrib><creatorcontrib>Korfel, Agnieszka</creatorcontrib><creatorcontrib>Thiel, Eckhard</creatorcontrib><creatorcontrib>Hebart, Holger</creatorcontrib><creatorcontrib>Simon, Matthias</creatorcontrib><creatorcontrib>Weller, Michael</creatorcontrib><creatorcontrib>Linnebank, Michael</creatorcontrib><creatorcontrib>Herrlinger, Ulrich</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Journal of neuro-oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kurzwelly, Delia</au><au>Knop, Stefan</au><au>Guenther, Markus</au><au>Loeffler, Juergen</au><au>Korfel, Agnieszka</au><au>Thiel, Eckhard</au><au>Hebart, Holger</au><au>Simon, Matthias</au><au>Weller, Michael</au><au>Linnebank, Michael</au><au>Herrlinger, Ulrich</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population</atitle><jtitle>Journal of neuro-oncology</jtitle><stitle>J Neurooncol</stitle><addtitle>J Neurooncol</addtitle><date>2010-11-01</date><risdate>2010</risdate><volume>100</volume><issue>2</issue><spage>187</spage><epage>192</epage><pages>187-192</pages><issn>0167-594X</issn><eissn>1573-7373</eissn><abstract>Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-Hodgkin’s lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms affecting methionine metabolism for potential association with the development of PCNSL. We observed underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine
S
-methyltransferase (
MTR
) c.2756A > G (D919G) missense polymorphism among PCNSL patients (
P
= 0.045; odds ratio (OR) = 0.65; 0.43–0.99). Furthermore, for the methylenetetrahydrofolate reductase (
MTHFR
) c.1298A > C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (
P
= 0.026; OR = 1.57; 1.05–2.34). There were no associations of the other polymorphisms investigated (
MTHFR
c.677C > T, transcobalamin 2 (
Tc2
) c.776C > G, cystathionin beta-synthase (
CBS
) c.844_855ins68, reduced folate carrier-1 (
RFC
-
1
) c.80G > A, thymidylate synthase (
TYMS
) 28-bp repeat, and dihydrofolate reductase (
DHFR
) c.594 + 59del19 bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>20237949</pmid><doi>10.1007/s11060-010-0154-4</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-594X |
| ispartof | Journal of neuro-oncology, 2010-11, Vol.100 (2), p.187-192 |
| issn | 0167-594X 1573-7373 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Adult Aged Aged, 80 and over Central Nervous System Neoplasms - epidemiology Central Nervous System Neoplasms - genetics Central Nervous System Neoplasms - metabolism Clinical Study - Patient Study European Continental Ancestry Group - genetics Female Folic Acid - genetics Folic Acid - metabolism Genetic Predisposition to Disease - epidemiology Genetic Predisposition to Disease - genetics Genotype Germany - epidemiology Humans Incidence Lymphoma - epidemiology Lymphoma - genetics Lymphoma - metabolism Male Medicine Medicine & Public Health Methionine - genetics Methionine - metabolism Middle Aged Neurology Oncology Polymorphism, Single Nucleotide |
| title | Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population |
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