{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T23:15:32Z","timestamp":1772234132008,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T00:00:00Z","timestamp":1100736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Folate and methionine are important nutrients in the \u201cone\u2010carbon\u201d metabolism that is closely associated with DNA synthesis and DNA methylation. Genetic variation in these pathways may change susceptibility to cancer development. We have previously reported associations between lymphoma risk and germline polymorphisms in genes of methylenetetrahydrofolate reductase (<jats:italic>MTHFR<\/jats:italic> C677T and A1298C) and methionine synthase (<jats:italic>MTR<\/jats:italic> A2756G), finding the genotype other than the <jats:italic>MTHFR 677CC<\/jats:italic>\/<jats:italic>1298AA<\/jats:italic> to confer a half\u2010risk compared to the <jats:italic>MTHFR 677CC<\/jats:italic>\/<jats:italic>1298AA<\/jats:italic> and a 3\u2010fold higher risk with the <jats:italic>MTR GG<\/jats:italic> genotype than the <jats:italic>AA<\/jats:italic>\/<jats:italic>AG<\/jats:italic> genotypes. To confirm the association and explore the histological difference, we extended the previous case series. A case\u2010control study was conducted in Japan with a total of 372 lymphoma cases and 500 noncancer controls examined for genotypes. The relative risks were estimated by unconditional logistic regression analysis. In overall analyses, the age\u2013sex adjusted odds ratio (OR) for the subjects harboring <jats:italic>MTHFR 677T<\/jats:italic> or <jats:italic>1298C<\/jats:italic> alleles relative to <jats:italic>677CC\/1298AA<\/jats:italic> genotype was 0.58 (95% confidence interval: 0.41\u20130.83, <jats:italic>P<\/jats:italic> = 0.002). The <jats:italic>MTR<\/jats:italic> GG genotype showed an OR of 1.75 (0.87\u20133.52, <jats:italic>P<\/jats:italic> = 0.114). These findings were validated in separate analyses of the 273 new incident cases. Subgroup analyses according to histological subtype [diffuse large B\u2010cell lymphoma (DLB), follicular lymphoma (FL), low\u2010grade lymphoma of mucosa associated lymphoid tissue (MALT), and others] illustrated similar associations with certain exceptions for FL and MALT. Our data showed an association between the <jats:italic>MTHFR<\/jats:italic> polymorphisms and malignant lymphoma risk for all histological subtypes, although the extent of contribution of these polymorphisms may differ somewhat with histological subtype. Lack of association with <jats:italic>MTR<\/jats:italic> polymorphism was also confirmed. Am. J. Hematol. 77:351\u2013357, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.20215","type":"journal-article","created":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T21:51:59Z","timestamp":1100814719000},"page":"351-357","source":"Crossref","is-referenced-by-count":41,"title":["Methylenetetrahydrofolate reductase gene (<i>MTHFR<\/i>) polymorphisms and reduced risk of malignant lymphoma"],"prefix":"10.1002","volume":"77","author":[{"given":"Keitaro","family":"Matsuo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Hamajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritsuro","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michinori","family":"Ogura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitoyo","family":"Kagami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Taji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Yasue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy E.","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Seto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Morishima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Tajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,11,18]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.5.869"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911113412007"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.12.3997"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.16.2023"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/301825"},{"key":"e_1_2_1_7_2","first-page":"1098","article-title":"Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer","volume":"57","author":"Ma J","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.3205"},{"key":"e_1_2_1_9_2","first-page":"513","article-title":"Methylenetetrahydrofolate reductase, diet, and risk of colon cancer","volume":"8","author":"Slattery ML","year":"1999","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12810"},{"key":"e_1_2_1_11_2","first-page":"65","volume-title":"Folic acid metabolism in health and disease","author":"Shane B","year":"1990"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.12.1867"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061408298"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.03140.x"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009113391"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03502.x"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00051676"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(96)00297-1"},{"key":"e_1_2_1_20_2","first-page":"602","article-title":"No substantial difference in genotype frequencies of interleukin and myeloperoxidase polymorphisms between malignant lymphoma patients and non\u2010cancer controls","volume":"86","author":"Matsuo K","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_1_21_2","first-page":"99","article-title":"Gene\u2010environment interaction and polymorphism studies of cancer risk in the Hospital\u2010based Epidemiologic Research Program at Aichi Cancer Center II (HERPACC\u2010II)","volume":"2","author":"Hamajima N","year":"2001","journal-title":"Asian Pac J Cancer Prev"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2272(199911)17:4<298::AID-GEPI5>3.0.CO;2-V"},{"key":"e_1_2_1_23_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1086\/302784","article-title":"The 1298(A\u2192C) mutation of methylenetetrahydrofolate reductase should be designated to the 1289 position of the gene","volume":"66","author":"Donnelly JG","year":"2000","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3290"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00261686"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/22.7.1019"},{"key":"e_1_2_1_27_2","first-page":"1089","article-title":"The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome damage in human lymphocytes in vitro","volume":"10","author":"Crott JW","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104589"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/15.7.1405"},{"key":"e_1_2_1_30_2","first-page":"1894","article-title":"Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate\/methyl\u2010deficient rats","volume":"55","author":"Pogribny IP","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/65.1.46"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.7.1204"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002725200"},{"key":"e_1_2_1_34_2","first-page":"849","article-title":"Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene","volume":"9","author":"Stern LL","year":"2000","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00469-X"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.5.1773"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261469998"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04220.x"},{"key":"e_1_2_1_39_2","first-page":"197","article-title":"Allele Frequencies of 25 polymorphisms pertaining to cancer risk for Japanese, Koreans and Chinese","volume":"3","author":"Hamajima N","year":"2002","journal-title":"Asian Pac J Cancer Prev"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008337900349"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.1.231"},{"key":"e_1_2_1_42_2","first-page":"35","article-title":"A model of practical cancer prevention for out\u2010patients visiting a hospital: the Hospital\u2010based Epidemiologic Research Program at Aich Cancer Center (HERPACC)","volume":"1","author":"Tajima K","year":"2000","journal-title":"Asian Pac J Cancer Prev"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.20215","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.20215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T22:04:02Z","timestamp":1700172242000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.20215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11,18]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,12]]}},"alternative-id":["10.1002\/ajh.20215"],"URL":"https:\/\/doi.org\/10.1002\/ajh.20215","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,11,18]]}}}