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

Autor(es)

Tomita, Luciana Y. ^[1] ; D'Almeida, Vania ^[2] ; Villa, Luisa L. ^{[3, 4]} ; Franco, Eduardo L. ^[5] ; Cardoso, Marly A. ^[6] ; Grp, BRINCA Study

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Prevent Med, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Radiol & Oncol, Sao Paulo - Brazil

^[4] Canc Inst Sao Paulo State, Sao Paulo - Brazil

^[5] McGill Univ, Div Canc Epidemiol, Montreal, PQ - Canada

^[6] Univ Sao Paulo, Sch Publ Hlth, Dept Nutr, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Nutrition; v. 143, n. 12, p. 2007-2014, DEC 2013.
• Citações Web of Science: 10

Resumo

High 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. (AU)

• Processo FAPESP: 07/53043-8 - Prevalencia de polimorfismos relacionados ao metabolismo da homocisteina e associacao com fatores dieteticos e hiperomocisteinemia em mulheres de baixa renda de sao paulo.
• Beneficiário: Marly Augusto Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/11184-0 - Consumo alimentar e níveis séricos de micronutrientes: associação com lesões neoplásicas do colo uterino
• Beneficiário: Luciana Yuki Tomita
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 03/03013-4 - Consumo alimentar e níveis séricos de micronutrientes: associação com lesões neoplásicas do colo uterino
• Beneficiário: Marly Augusto Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular