{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T09:40:32Z","timestamp":1695807632949},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T00:00:00Z","timestamp":1464566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Elevated homocysteine levels are a risk factor for breast cancer, although the mechanism underlying this effect is unknown. Genome\u2010wide association studies were used to systematically identify genetic variants which were significantly associated with the circulating homocysteine concentration. To examine the role of homocysteine\u2010related variants in the occurrence of breast cancer, we investigated the association between these variants and breast cancer in a Han Chinese population. Five variants of genome\u2010wide significant homocysteine\u2010related genes were selected for the analysis in a case\u2013control study, with a total of 487 patients with breast cancer and 605 controls. We found that none of the studied polymorphisms were related to the altered breast cancer risk. In the haplotypic analysis, the 5,10\u2010methylenetetrahydrofolate reductase (<jats:italic>MTHFR<\/jats:italic>) haplotypes rs12085006A\/rs1999594G\/rs1801133C (OR\u2009=\u20093.44, 95% CI\u2009=\u20091.58\u20137.50, <jats:italic>P<\/jats:italic>\u2009=\u20090.0019) and rs12085006A\/rs1999594G\/rs1801133T (OR\u2009=\u200916.21, 95% CI\u2009= 2.19\u2013 120.32, <jats:italic>P<\/jats:italic>\u2009=\u20090.0065) were significantly associated with an increased breast cancer risk when compared with the wild\u2010type haplotype. Both of the risky <jats:italic>MTHFR<\/jats:italic> haplotypes were correlated with decreased <jats:italic>MTHFR<\/jats:italic> gene expression and elevated homocysteine concentrations, indicating a genetic component for hyperhomocysteinemia. The <jats:italic>MTHFR<\/jats:italic> haplotypes reconstructed with homocysteine\u2010related variants were associated with the occurrence of breast cancer. This finding further emphasizes the importance of homocysteine metabolism genes in breast carcinogenesis and highlights the interplay of diet, genetics, and human cancers. \u00a9 2016 IUBMB Life, 68(7):526\u2013534, 2016<\/jats:p>","DOI":"10.1002\/iub.1509","type":"journal-article","created":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T05:06:41Z","timestamp":1464584801000},"page":"526-534","source":"Crossref","is-referenced-by-count":8,"title":["Haplotypes of the <i>MTHFR<\/i> gene are associated with an increased risk of breast cancer in a Han Chinese population in Gansu province"],"prefix":"10.1002","volume":"68","author":[{"given":"Ailing","family":"Song","sequence":"first","affiliation":[{"name":"Key Laboratory of Digestive System Tumors of Gansu Province  Gansu People's Republic of China"},{"name":"Depertment of Surgery The Second Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Digestive System Tumors of Gansu Province  Gansu People's Republic of China"},{"name":"Depertment of Surgery The Second Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Digestive System Tumors of Gansu Province  Gansu People's Republic of China"},{"name":"Depertment of Surgery The Second Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Depertment of Breast Surgery The First Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Digestive System Tumors of Gansu Province  Gansu People's Republic of China"},{"name":"Depertment of Surgery The Second Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaokang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Digestive System Tumors of Gansu Province  Gansu People's Republic of China"},{"name":"Depertment of Surgery The Second Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shen","family":"Lan","sequence":"additional","affiliation":[{"name":"Depertment of Surgery The Second Hospital of Lanzhou University Lanzhou Gansu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,5,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.12.61"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25516"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11058-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804093381507"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.16.2015"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7374.1202"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020122600402"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/77.2.467"},{"key":"e_1_2_7_10_1","first-page":"4131","article-title":"Determinants of homocysteine levels in colorectal and breast cancer patients","volume":"29","author":"Ferroni P.","year":"2009","journal-title":"Anticancer Res."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2007.00907.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2010.492088"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1897-4287-12-2"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-006-9278-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.24.012003.132418"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-006-0432-9"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3648"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(02)00092-X"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(02)00174-2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(91)90189-A"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00029-5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1274"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2009.57"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-03-0273"},{"key":"e_1_2_7_25_1","first-page":"4805","article-title":"Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil","volume":"32","author":"Barbosa R.","year":"2012","journal-title":"Anticancer Res."},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-010-0755-9"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.06.054"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21830"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-122"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.02.011"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp428"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl268"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.11.2698"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-1037"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djj440"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.2.129"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.266"},{"key":"e_1_2_7_38_1","first-page":"7136","article-title":"Dietary folate intake and breast cancer risk results from the Shanghai Breast Cancer Study","volume":"61","author":"Shrubsole M. J.","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1041>3.0.CO;2-#"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl108"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC4602_05"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0532"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/95.5.373"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5502_3"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC4402_03"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.17.1632"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-006-0053-3"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.3.1357"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.36.040196.001223"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050776"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101253440407"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jncimonographs.a024245"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.2307\/3433371"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06920.2000"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00017-0"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10416"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206440"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fiub.1509","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.1509","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T21:48:43Z","timestamp":1695764923000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.1509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,30]]},"references-count":56,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1002\/iub.1509"],"URL":"https:\/\/doi.org\/10.1002\/iub.1509","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,30]]}}}