Polymorphisms in Genes Involved in Folate Metabolism Modify the Association of Dietary and Circulating Folate and Vitamin B-6 with Cervical Neoplasia

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorTOMITA, Luciana Y.
dc.contributor.authorD'ALMEIDA, Vania
dc.contributor.authorVILLA, Luisa L.
dc.contributor.authorFRANCO, Eduardo L.
dc.contributor.authorCARDOSO, Marly A.
dc.contributor.groupauthorBRINCA Study Grp
dc.date.accessioned2014-01-28T22:20:04Z
dc.date.available2014-01-28T22:20:04Z
dc.date.issued2013
dc.description.abstractHigh folate intake has been suggested as an important factor in cancer prevention; however, previous studies on the relation among folate intake, serum folate, and plasma homocysteine (hcy) are controversial. We conducted a hospital-based, case-control study in Brazil investigating associations between dietary and circulating vitamins B-6 and B-12 and folate, hcy, genotypes of folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), methionine synthase reductase (MTRR A66G), and reduced folate carrier (RFC1 G80A) and risk of cervical intraepithelial neoplasia (CIN) grades 1 (CIN1), 2 (CIN2), and 3 (CIN3). The study was composed by 453 controls, 140 CIN1, 126 CIN2, and 231 CIN3. We investigated the joint effects of genetic variants of folate-related genes using genetic risk scores (GRSs) by summing the number of risk alleles for CIN1 and CIN2+ (CIN2 and CIN3 cases). The OR (95% CI) for CIN1 and CIN2+ per each risk allele were 1.29 (1.01, 1.65) and 1.22 (1.01, 1.46), respectively. An association between folate intake and CIN2+ was observed only after stratification according to GRS: crude OR (95% CI) for lower folate intake and GRS >= 4 was 1.67 (0.92, 3.04) (P-trend < 0.001) compared with higher folate intake (above the median) and GRS <= 3. The CIN2+ risk of lower serum vitamin B-6 and GRS >= 4 was 2.14 (0.92, 5.02) (P-trend = 0.05) and lower serum folate (below the median) and GRS >= 4 was 0.49 (0.20, 1.17) (P-trend = 0.05) after adjustment for confounding variables and human papillomavirus infection. Our data suggest that polymorphisrns in genes related to folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia.
dc.description.indexMEDLINE
dc.description.sponsorshipSao Paulo State Research Foundation (FAPESP) [03/03013-4, 2007/53043-8]
dc.description.sponsorshipBrazilian National Counsel of Technological and Scientific Development (CNPq) [473043/03-3, 300167/97-0]
dc.description.sponsorshipFAPESP [02/11184-0]
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [BEX3775/05-4]
dc.description.sponsorshipCAPES [PRODOC 0091/08-1]
dc.identifier.citationJOURNAL OF NUTRITION, v.143, n.12, p.2007-2014, 2013
dc.identifier.doi10.3945/jn.113.182212
dc.identifier.issn0022-3166
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/4014
dc.language.isoeng
dc.publisherAMER SOC NUTRITION-ASN
dc.relation.ispartofJournal of Nutrition
dc.rightsrestrictedAccess
dc.rights.holderCopyright AMER SOC NUTRITION-ASN
dc.subject.othermethylenetetrahydrofolate reductase mthfr
dc.subject.otherhuman-papillomavirus infection
dc.subject.othertotal plasma homocysteine
dc.subject.othermulticentric case-control
dc.subject.othermethionine synthase ms
dc.subject.otherintraepithelial neoplasia
dc.subject.otherfolic-acid
dc.subject.othercancer-risk
dc.subject.otherserum micronutrients
dc.subject.otherdna methylation
dc.subject.wosNutrition & Dietetics
dc.titlePolymorphisms in Genes Involved in Folate Metabolism Modify the Association of Dietary and Circulating Folate and Vitamin B-6 with Cervical Neoplasia
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryCanadá
hcfmusp.affiliation.countryisoca
hcfmusp.author.externalTOMITA, Luciana Y.:Univ Fed Sao Paulo, Dept Prevent Med, Sao Paulo, Brazil
hcfmusp.author.externalD'ALMEIDA, Vania:Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, Brazil
hcfmusp.author.externalFRANCO, Eduardo L.:McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada
hcfmusp.author.externalCARDOSO, Marly A.:Univ Sao Paulo, Sch Publ Hlth, Dept Nutr, Sao Paulo, Brazil
hcfmusp.citation.scopus18
hcfmusp.contributor.author-fmusphcLUISA LINA VILLA
hcfmusp.description.beginpage2007
hcfmusp.description.endpage2014
hcfmusp.description.issue12
hcfmusp.description.volume143
hcfmusp.origemWOS
hcfmusp.origem.pubmed24089416
hcfmusp.origem.scopus2-s2.0-84888427333
hcfmusp.origem.wosWOS:000327571500019
hcfmusp.publisher.cityBETHESDA
hcfmusp.publisher.countryUSA
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hcfmusp.remissive.sponsorshipCAPES
hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
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