{"id":"https://openalex.org/W2167805920","doi":"https://doi.org/10.1093/jnci/djm105","title":"One-Carbon Metabolism, Colorectal Carcinogenesis, Chemoprevention--with Caution","display_name":"One-Carbon Metabolism, Colorectal Carcinogenesis, Chemoprevention--with Caution","publication_year":2007,"publication_date":"2007-08-08","ids":{"openalex":"https://openalex.org/W2167805920","doi":"https://doi.org/10.1093/jnci/djm105","mag":"2167805920","pmid":"https://pubmed.ncbi.nlm.nih.gov/17686821"},"language":"en","primary_location":{"id":"doi:10.1093/jnci/djm105","doi":"https://doi.org/10.1093/jnci/djm105","is_oa":false,"landing_page_url":"https://doi.org/10.1093/jnci/djm105","pdf_url":null,"source":{"id":"https://openalex.org/S98010888","display_name":"JNCI Journal of the National Cancer Institute","issn_l":"0027-8874","issn":["0027-8874","1460-2105"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"JNCI Journal of the National Cancer Institute","raw_type":"journal-article"},"volume":null,"type":"editorial","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5053374075","display_name":"Regina G. Ziegler","orcid":"https://orcid.org/0000-0002-5100-9852","observed_orcids":["https://orcid.org/0000-0002-5100-9852"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"R. G. Ziegler","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5003034094","display_name":"Unhee Lim","orcid":"https://orcid.org/0000-0001-6221-7190","observed_orcids":["https://orcid.org/0000-0001-6221-7190"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"U. Lim","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5436,"currency":"USD","value_usd":5436},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":18,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"99","issue":"16","first_page":"1214","last_page":"1215"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10499","display_name":"Folate and B Vitamins Research","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2916","display_name":"Nutrition and Dietetics"},"field":{"id":"https://openalex.org/fields/29","display_name":"Nursing"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10499","display_name":"Folate and B Vitamins Research","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2916","display_name":"Nutrition and Dietetics"},"field":{"id":"https://openalex.org/fields/29","display_name":"Nursing"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10269","display_name":"Epigenetics and DNA Methylation","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/one-carbon-metabolism","display_name":"one-carbon metabolism","score":0.9240000247955322},{"id":"https://openalex.org/keywords/colorectal-carcinogenesis","display_name":"colorectal carcinogenesis","score":0.859000027179718},{"id":"https://openalex.org/keywords/colorectal-adenoma","display_name":"colorectal adenoma","score":0.9570000171661377},{"id":"https://openalex.org/keywords/chemoprevention","display_name":"chemoprevention","score":0.8830000162124634},{"id":"https://openalex.org/keywords/folate-intake","display_name":"folate intake","score":0.8420000076293945},{"id":"https://openalex.org/keywords/b-vitamins","display_name":"B vitamins","score":0.6729999780654907},{"id":"https://openalex.org/keywords/alcohol-consumption","display_name":"alcohol consumption","score":0.597000002861023},{"id":"https://openalex.org/keywords/folate-status","display_name":"folate status","score":0.5410000085830688},{"id":"https://openalex.org/keywords/methionine","display_name":"methionine","score":0.6779999732971191},{"id":"https://openalex.org/keywords/dna-methylation","display_name":"DNA methylation","score":0.7369999885559082},{"id":"https://openalex.org/keywords/s-adenosylmethionine","display_name":"S-adenosylmethionine","score":0.8560000061988831},{"id":"https://openalex.org/keywords/homocysteine","display_name":"homocysteine","score":0.7770000100135803},{"id":"https://openalex.org/keywords/genetic-polymorphism","display_name":"genetic polymorphism","score":0.7910000085830688},{"id":"https://openalex.org/keywords/colorectal-cancer-risk","display_name":"colorectal cancer risk","score":0.6050000190734863},{"id":"https://openalex.org/keywords/vitamin-b12-deficiency","display_name":"vitamin B12 deficiency","score":0.49300000071525574}],"concepts":[{"id":"https://openalex.org/C190727270","wikidata":"https://www.wikidata.org/wiki/Q874745","display_name":"DNA methylation","level":4,"score":0.5405297875404358},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4908517003059387},{"id":"https://openalex.org/C3020471959","wikidata":"https://www.wikidata.org/wiki/Q183206","display_name":"B vitamins","level":2,"score":0.4722791612148285},{"id":"https://openalex.org/C41091548","wikidata":"https://www.wikidata.org/wiki/Q26939","display_name":"Epigenetics","level":3,"score":0.4677211046218872},{"id":"https://openalex.org/C2780912031","wikidata":"https://www.wikidata.org/wiki/Q180341","display_name":"Methionine","level":3,"score":0.46505221724510193},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4596083164215088},{"id":"https://openalex.org/C2779750884","wikidata":"https://www.wikidata.org/wiki/Q187706","display_name":"Vitamin B12","level":2,"score":0.45008060336112976},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.44287580251693726},{"id":"https://openalex.org/C2777090595","wikidata":"https://www.wikidata.org/wiki/Q192466","display_name":"Homocysteine","level":2,"score":0.42709311842918396},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.4212418794631958},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.2190525233745575},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.14250457286834717},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.13010752201080322},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001622","descriptor_name":"Betaine","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D002244","descriptor_name":"Carbon","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002471","descriptor_name":"Cell Transformation, Neoplastic","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D002471","descriptor_name":"Cell Transformation, Neoplastic","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D002794","descriptor_name":"Choline","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D004032","descriptor_name":"Diet","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005492","descriptor_name":"Folic Acid","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008715","descriptor_name":"Methionine","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000209","qualifier_name":"etiology","is_major_topic":false},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000453","qualifier_name":"epidemiology","is_major_topic":true},{"descriptor_ui":"D015179","descriptor_name":"Colorectal Neoplasms","qualifier_ui":"Q000517","qualifier_name":"prevention & control","is_major_topic":true},{"descriptor_ui":"D018890","descriptor_name":"Chemoprevention","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1093/jnci/djm105","doi":"https://doi.org/10.1093/jnci/djm105","is_oa":false,"landing_page_url":"https://doi.org/10.1093/jnci/djm105","pdf_url":null,"source":{"id":"https://openalex.org/S98010888","display_name":"JNCI Journal of the National Cancer Institute","issn_l":"0027-8874","issn":["0027-8874","1460-2105"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"JNCI Journal of the National Cancer Institute","raw_type":"journal-article"},{"id":"pmid:17686821","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/17686821","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the National Cancer Institute","raw_type":"Comment"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.974.6790","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.974.6790","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://jnci.oxfordjournals.org/content/99/16/1214.full.pdf","raw_type":"text"},{"id":"pmh:oai:open-archive.highwire.org:jnci:djm105v1","doi":null,"is_oa":false,"landing_page_url":"http://jnci.oxfordjournals.org/cgi/content/short/djm105v1","pdf_url":null,"source":{"id":"https://openalex.org/S4406923041","display_name":"HighWire Press Open Archive","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"TEXT"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9907000064849854}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":16,"referenced_works":["https://openalex.org/W1979942764","https://openalex.org/W2014628140","https://openalex.org/W2029607729","https://openalex.org/W2087824865","https://openalex.org/W2099930946","https://openalex.org/W2103953940","https://openalex.org/W2108210899","https://openalex.org/W2113665122","https://openalex.org/W2120208703","https://openalex.org/W2128011015","https://openalex.org/W2139126351","https://openalex.org/W2142877787","https://openalex.org/W2154211873","https://openalex.org/W2154888525","https://openalex.org/W2155614484","https://openalex.org/W4285719527"],"related_works":["https://openalex.org/W2778896402","https://openalex.org/W7096349837","https://openalex.org/W2265136525","https://openalex.org/W2129408317","https://openalex.org/W2107604852","https://openalex.org/W7097353842","https://openalex.org/W1882281882","https://openalex.org/W2106612866","https://openalex.org/W2586504085","https://openalex.org/W200994749"],"abstract_inverted_index":{"One-carbon":[0,106],"metabolism":[1,22,63,84,107,143,338,966,1043,1255,1308,1333],"comprises":[2],"a":[3,54,124,149,411,500,541,580,602,609,710,720,849,862,886,1065,1078,1166,1310],"network":[4],"of":[5,28,37,45,82,95,101,111,117,173,226,231,269,277,310,315,336,371,390,460,483,492,495,502,504,528,565,592,632,646,651,659,691,729,732,745,774,803,852,857,875,890,906,924,979,1011,1017,1021,1027,1035,1052,1081,1100,1126,1168,1171,1175,1235,1297,1348],"integrated":[6],"biochemical":[7],"pathways":[8],"that":[9,201,308,454,625,840,964,973,987,1191,1202,1229,1257,1291,1375],"donate,":[10],"and":[11,32,34,93,132,153,175,179,192,210,239,251,259,272,287,333,363,379,394,419,430,439,474,485,509,531,567,634,639,661,664,716,793,811,833,842,926,945,956,1013,1044,1055,1075,1104,1174,1208,1265,1334,1345,1357,1364,1373,1383],"regenerate,":[12],"the":[13,26,29,35,43,68,138,162,168,232,243,275,278,368,422,493,523,563,573,590,626,652,655,675,699,704,725,735,746,772,798,855,872,882,939,977,993,1002,1053,1098,1113,1120,1142,1224,1241,1258,1271,1349,1371],"one-carbon":[14,21,62,83,142,316,337,386,412,570,682,965,1018,1042,1254,1282,1307,1332],"moieties":[15],"needed":[16],"for":[17,25,75,248,436,444,806,1001,1090,1123,1151,1223,1377],"physiologic":[18,1320],"processes.":[19],"Efficient":[20],"is":[23,73,245,264,636,1228,1256,1339,1352,1366],"required":[24,74],"biosynthesis":[27],"purines,":[30],"adenine":[31],"guanine,":[33],"conversion":[36],"uridylate":[38],"to":[39,57,59,197,223,407,414,416,539,546,614,678,761,861,898,1092,1139,1155,1161,1182],"thymidylate,":[40],"which":[41,72,102,118,184,328,962],"prevents":[42],"misincorporation":[44],"uracil":[46],"into":[47],"DNA":[48,76,89,91],"(":[49,78,189,281,302,322,339,353,374,447,478,519,576,619,671,808,1109,1215,1244,1322],"1":[50,79,1088],").":[51,80,285,304,324,355,376,449,480,521,578,621,1111,1219,1248,1330],"By":[52],"donating":[53],"methyl":[55,70,424,461],"group":[56],"homocysteine":[58,415,548],"create":[60],"methionine,":[61,311,473],"also":[64,128,319,594,717,985,1059],"generates":[65],"S":[66,426],"-adenosylmethionine,":[67],"universal":[69,423],"donor,":[71,425],"methylation":[77],"Disruption":[81],"can,":[85],"therefore,":[86],"interfere":[87],"with":[88,186,266,300,330,344,534,553,596,601,643,688,741,848,866,879,952,958,1033,1077,1199],"replication,":[90],"repair,":[92],"regulation":[94],"gene":[96],"expression":[97],"through":[98],"methylation,":[99],"each":[100],"could":[103,156,202],"promote":[104],"carcinogenesis.":[105],"requires":[108],"optimal":[109],"activity":[110,195],"25":[112],"or":[113,557,722,749,934,1301,1303],"more":[114,383,1340],"enzymes,":[115],"some":[116,644],"depend":[119],"on":[120,161,170,1048,1194],"not":[121,295,910,929,1030,1060,1096,1317],"only":[122],"folate,":[123,686,1029,1315],"B":[125],"vitamin,":[126],"but":[127,242,984],"vitamins":[129],"B-12,":[130],"B-6,":[131],"B-2":[133],"(riboflavin)":[134],"as":[135,148,385,569,814,816,996,1274],"coenzymes.":[136],"Over":[137],"past":[139],"15":[140,1327],"years,":[141],"has":[144,220,451,515],"received":[145,382],"increasing":[146,867],"attention":[147,384],"process":[150],"whereby":[151],"diet":[152],"genetic":[154,199],"variation":[155,628],"modulate":[157],"cancer":[158,171,250,273,666],"risk.":[159,1004],"Based":[160],"biochemistry,":[163],"hypotheses":[164,1040],"were":[165,751,756],"generated":[166],"about":[167,1041,1253],"influence":[169],"risk":[172,268,301,690,851,856,889,915,947,1034,1122,1150,1170],"folate":[174,178,187,218,262,291,331,349,360,364,378,437,441,477,555,617,933,954,1195,1203,1209,1278],"B-vitamin":[176,180],"intake;":[177,869],"status;":[181],"alcohol":[182,326,960],"use,":[183],"interferes":[185,329],"bioavailability":[188],"2":[190,340],");":[191],"altered":[193],"enzyme":[194],"related":[196],"common":[198,512],"polymorphisms\u2014hypotheses":[200],"be":[203,320,641,846,968,999],"tested":[204],"in":[205,274,388,511,572,583,605,629,654,703,714,871,881,992,1240,1262,1270,1279,1337,1359],"animal":[206,1192],"experiments,":[207],"epidemiologic":[208,215,279,657,1287],"studies,":[209,216],"randomized":[211,1069],"clinical":[212,1070,1186],"trials.":[213],"In":[214,256,356,428,522,579,648,1064],"low":[217,261,352,554,615,953],"intake":[219,263,309,350,487,527,556,588,618,631,663,767,782,802,820,844,908,936,944,955,1010,1026],"been":[221,297,452,489,517,1061,1197],"linked":[222,613],"increased":[224,267,345,860,1107,1154,1169],"risks":[225],"several":[227,1200,1285],"cancers,":[228],"including":[229],"cancers":[230],"breast,":[233],"ovary,":[234],"cervix,":[235],"esophagus,":[236],"stomach,":[237],"pancreas,":[238],"lymphoid":[240],"tissues,":[241],"evidence":[244],"most":[246],"extensive":[247],"colorectal":[249,254,270,692,853,858,982,1036,1045,1082,1102,1131,1213,1242],"its":[252,395,1298,1335],"precursor,":[253],"adenoma.":[255,693,1037],"both":[257],"men":[258,1074],"women,":[260],"associated":[265,299,343,600,687,847,1032],"adenoma":[271,744,859,946,1132],"majority":[276],"studies":[280,389,482,623,1288],"3":[282,303,323,354,1117],",":[283,1217,1246,1324,1326,1328],"4":[284,1323],"Serum":[286],"red":[288,789],"blood":[289],"cell":[290],"have":[292,381,488,540,1058,1106,1196,1289],"generally,":[293],"although":[294],"always,":[296],"inversely":[298,1031],"Limited":[305],"data":[306],"suggest":[307,624],"an":[312,1145],"essential":[313],"source":[314],"groups,":[317],"may":[318,967,1316],"protective":[321],"High":[325],"consumption,":[327],"utilization":[332],"other":[334,988,1385],"aspects":[335],"),":[341],"was":[342,351,537,599,696,776,795,838,909,928,932,948,1133,1165],"risk,":[346,667],"especially":[347],"when":[348],"rodent":[357],"models,":[358],"usually":[359],"depletion":[361],"enhanced":[362],"supplementation":[365,1210],"protected":[366],"against":[367],"early":[369,1238],"stages":[370],"intestinal":[372],"carcinogenesis":[373,1214,1338],"5":[375,1216],"Although":[377,836],"methionine":[380,418,935],"donors":[387,571,683],"chronic":[391],"disease,":[392],"choline":[393,433,445,484,530,566,587,633,660,781,841,868,876,925,943,974,997,1012],"metabolite":[396],"betaine":[397,486,510,532,568,635,662,819,843,907,927],"merit":[398],"comparable":[399,1319],"consideration.":[400],"Like":[401],"5-methyl":[402],"tetrahydrofolate,":[403],"choline,":[404,470,506],"once":[405],"oxidized":[406],"betaine,":[408,1014],"can":[409,434,442,640,1205,1211],"transfer":[410],"moiety":[413],"produce":[417],"then":[420],"generate":[421],"-adenosylmethionine.":[427],"animals":[429],"humans,":[431],"dietary":[432,440,529,630,989,1028],"compensate":[435,443],"deprivation":[438,446],"6":[448,1093],"It":[450],"estimated":[453,595],"humans":[455],"ingest":[456],"approximately":[457,465,700,812],"50":[458],"mmol":[459],"groups":[462],"per":[463],"day;":[464],"60%":[466],"are":[467],"derived":[468],"from":[469,472,476,768,788,826],"20%":[471],"10%\u201320%":[475],"7":[479,809],"Epidemiologic":[481],"sparse":[490],"because":[491,1296,1304],"absence":[494],"food":[496,1266,1277,1314],"composition":[497],"data.":[498],"However,":[499,938,1284],"database":[501,536,677],"concentrations":[503],"free":[505],"choline-containing":[507],"phospholipids,":[508],"US":[513],"foods":[514,995],"recently":[516,1066],"developed":[518],"8":[520],"Framingham":[524],"Offspring":[525],"Study,":[526],"assessed":[533],"this":[535,597,649],"found":[538],"statistically":[542,863,911],"significant":[543,864,912],"inverse":[544,904],"relationship":[545],"circulating":[547],"concentrations,":[549],"particularly":[550],"among":[551,698,950,1072,1178],"participants":[552,1179],"who":[558,708],"consumed":[559],"alchohol,":[560],"thus":[561],"confirming":[562],"role":[564,1336],"general":[574],"population":[575],"9":[577],"case\u2013control":[581],"study":[582,658],"California,":[584],"higher":[585,959],"maternal":[586],"around":[589],"time":[591],"conception,":[593],"database,":[598],"50%":[603],"reduction":[604],"neural":[606],"tube":[607],"defects,":[608],"birth":[610],"defect":[611],"previously":[612],"perinatal":[616],"10":[620],"Both":[622],"normal":[627],"physiologically":[637],"important":[638,1015],"measured":[642],"degree":[645],"validity.":[647],"issue":[650],"Journal,":[653],"first":[656,1114],"subsequent":[665,726,1101],"Cho":[668],"et":[669],"al.":[670],"11":[672],")":[673,810],"use":[674],"new":[676,1130],"examine":[679],"whether":[680],"these":[681],"are,":[684],"like":[685],"reduced":[689,850],"Their":[694],"analysis":[695],"conducted":[697],"39000":[701],"women":[702,733,740,807,870,880,1076],"Nurses\u2019":[705],"Health":[706],"Study":[707],"completed":[709],"130-item":[711],"food-frequency":[712,754],"questionnaire":[713],"1984":[715,736],"reported":[718],"having":[719],"sigmoidoscopy":[721],"colonoscopy":[723],"during":[724],"18":[727],"years":[728,1094,1118,1148],"follow-up":[730],"(\u223c50%":[731],"completing":[734],"questionnaire).":[737],"Approximately":[738],"2400":[739],"histologically":[742],"confirmed":[743],"distal":[747],"colon":[748],"rectum":[750],"identified.":[752],"Repeat":[753],"questionnaires":[755,770],"given":[757],"every":[758],"2\u20134":[759],"years;":[760],"estimate":[762],"long-term":[763],"intake,":[764,877,961],"cumulative":[765],"average":[766],"all":[769],"before":[771],"date":[773],"endoscopy":[775],"calculated.":[777],"Mean":[778],"energy-adjusted":[779,818],"total":[780],"(331":[783],"\u00b1":[784,822],"80":[785],"mg/day),":[786,824],"primarily":[787,825],"meat,":[790],"eggs,":[791],"poultry,":[792],"milk,":[794],"less":[796],"than":[797,1313,1342],"current":[799,1050],"recommended":[800],"daily":[801],"425":[804],"mg/d":[805,1089],"twice":[813],"high":[815],"mean":[817],"(189":[821],"97":[823],"spinach,":[827],"white":[828],"bread,":[829],"cold":[830],"cereal,":[831],"pasta,":[832],"dark":[834],"bread.":[835],"it":[837,1108,1305],"hypothesized":[839],"would":[845],"adenoma,":[854,1083],"extent":[865],"highest":[873],"quintile":[874],"compared":[878],"lowest":[883],"quintile,":[884],"had":[885],"multivariable-adjusted":[887],"relative":[888,914,1121],"1.45":[891],"(95%":[892,1135,1157],"confidence":[893],"interval":[894],"[CI]":[895],"=":[896,919,1137,1159],"1.27":[897],"1.67;":[899],"Ptrend":[900],"<.001).":[901],"The":[902,921,970,1185],"weak":[903],"association":[905,941],"(multivariable-adjusted":[913],"between":[916,942],"extreme":[917],"quintiles":[918],"0.90).":[920],"combined":[922],"effect":[923],"estimated,":[930],"nor":[931],"integrated.":[937],"positive":[940],"strongest":[949],"those":[951,957],"suggests":[963],"involved.":[969],"authors":[971],"conjecture":[972],"might":[975,998,1105],"stimulate":[976],"growth":[978,1234],"already":[980],"initiated":[981],"adenomas":[983,1103,1177],"recognize":[986],"factors":[990],"concentrated":[991],"same":[994,1272],"responsible":[1000],"elevated":[1003],"Nevertheless,":[1005],"they":[1006],"cannot":[1007],"explain":[1008],"why":[1009],"sources":[1016],"units":[1019],"capable":[1020],"remethylating":[1022],"homocysteine,":[1023],"was,":[1024],"unlike":[1025],"Other":[1038],"reasonable":[1039,1221],"carcinogenesis,":[1046],"based":[1047],"our":[1049,1346],"understanding":[1051,1347],"biochemistry":[1054],"underlying":[1056,1350],"mechanisms,":[1057],"proven":[1062],"correct.":[1063],"published":[1067],"placebo-controlled":[1068],"trial":[1071,1187,1226],"1021":[1073],"recent":[1079,1286],"history":[1080],"supplemental":[1084,1230,1292],"folic":[1085,1124,1152,1183,1231,1259,1293],"acid":[1086,1125,1153,1232,1260],"at":[1087,1127,1141,1309],"up":[1091],"did":[1095],"reduce":[1097],"incidence":[1099],"12":[1110,1218,1245],"At":[1112],"colonoscopic":[1115],"follow-up,":[1116,1144],"later,":[1119,1149],"least":[1128],"one":[1129],"1.04":[1134],"CI":[1136,1158],"0.90":[1138],"1.20);":[1140],"second":[1143],"additional":[1146],"3\u20135":[1147],"1.13":[1156],"0.93":[1160],"1.37).":[1162],"Furthermore,":[1163],"there":[1164],"suggestion":[1167],"advanced":[1172],"lesions":[1173,1239],"multiple":[1176],"randomly":[1180],"assigned":[1181],"acid.":[1184],"investigators":[1188],"pointed":[1189],"out":[1190],"experiments":[1193],"inconsistent,":[1198],"suggesting":[1201],"deficiency":[1204],"protect":[1206],"against,":[1207],"enhance,":[1212],"A":[1220],"explanation":[1222],"unexpected":[1225],"results":[1227],"promoted":[1233],"undetected":[1236],"very":[1237],"mucosa":[1243],"13":[1247],"Still":[1249],"another":[1250],"plausible":[1251],"hypothesis":[1252],"used":[1261],"vitamin":[1263,1379,1381],"supplements":[1264],"fortification":[1267],"will":[1268],"function":[1269],"manner":[1273],"naturally":[1275],"occurring":[1276],"ensuring":[1280],"efficient":[1281],"metabolism.":[1283],"suggested":[1290],"acid,":[1294],"possibly":[1295],"structure,":[1299],"bioavailability,":[1300],"dose,":[1302],"enters":[1306],"different":[1311],"point":[1312],"provide":[1318],"benefits":[1321],"14":[1325],"16":[1329],"Clearly,":[1331],"complicated":[1341],"originally":[1343],"anticipated,":[1344],"mechanisms":[1351],"probably":[1353],"incomplete.":[1354],"More":[1355],"research,":[1356],"caution":[1358],"developing":[1360],"public":[1361],"health":[1362],"policy":[1363],"guidance,":[1365],"warranted.":[1367],"We":[1368],"should":[1369],"remember":[1370],"surprises":[1372],"complexities":[1374],"emerged":[1376],"\u03b2-carotene,":[1378],"E,":[1380],"C,":[1382],"selenium,":[1384],"initially":[1386],"promising":[1387],"chemopreventive":[1388],"agents.":[1389]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2018,"cited_by_count":2},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}