title: Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer.
abstract: Vascular Endothelial Growth Factor (VEGF) mediates angiogenesis, which is crucial for tumor development and progression. The present study aimed to evaluate the impact of VEGFA gene polymorphisms rs699947, rs833061, rs1570360, rs2010963 and rs3025039 on breast cancer features and prognosis. A cohort of Brazilian women (N = 1038) with unilateral non-metastatic breast cancer was evaluated. The association between VEGFA polymorphisms and histopathological features or pathological complete response (pCR) to neoadjuvant chemotherapy was evaluated by the Chi-square test, with calculation of the respective odds ratio (OR) and 95% confidence intervals (95% CI). The impact of individual categories on disease-free survival was evaluated using Kaplan-Meier curves and multivariate Cox proportional hazards regression models for calculation of adjusted hazard ratios (HRadjusted). Variant genotypes of rs699947 (CA + AA) were significantly associated with high-grade (G2 + G3) tumors (OR = 1.82; 95% CI = 1.15 - 2.89), and with shorter disease-free survival among patients treated with neoadjuvant chemotherapy followed by mastectomy (HRadjusted = 1.82; 95% CI = 1.16 - 2.86). Variant genotypes of rs833061 (TC + CC) were significantly associated with high-grade (G2 + G3) tumors (OR = 1.79; 95% CI = 1.12 - 2.84) and with positive lymph node status (OR = 1.34; 95% CI = 1.01 - 1.77), but showed no independent effect on disease-free survival. Variant haplotypes (*2 to *5) appear to favor pCR (OR = 7.1; 95% CI = 1.7 - 30.1). VEGFA genotyping may add to prognostic evaluation of breast cancer, with rs699947 being the most likely to contribute.
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.|b Programa de Saúde Pública e Meio Ambiente - Escola Nacional de Saúde Pública - FIOCRUZ , Rio de Janeiro , RJ , Brasil.
authors.forename: Hayra de Andrade
authors.initials: Hde A
authors.lastname: Vieira-Monteiro
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.|b Programa de Saúde Pública e Meio Ambiente - Escola Nacional de Saúde Pública - FIOCRUZ , Rio de Janeiro , RJ , Brasil.
authors.forename: Daniely Regina
authors.initials: DR
authors.lastname: Freitas-Alves
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.|c Division of Molecular Pathology, Netherlands Cancer Institute , Amsterdam , The Netherlands.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Sobral-Leite
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.|d Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro , Rio de Janeiro , RJ , Brasil.
authors.forename: João Marcos de Azevedo
authors.initials: JM
authors.lastname: Delou
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.
authors.forename: Sheyla Maria Torres
authors.initials: SM
authors.lastname: Goulart-Citrangulo
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.
authors.forename: Camila Telles
authors.initials: CT
authors.lastname: do Nascimento
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.|b Programa de Saúde Pública e Meio Ambiente - Escola Nacional de Saúde Pública - FIOCRUZ , Rio de Janeiro , RJ , Brasil.
authors.forename: Thales Nascimento
authors.initials: TN
authors.lastname: E Castro
authors.affiliation: b Programa de Saúde Pública e Meio Ambiente - Escola Nacional de Saúde Pública - FIOCRUZ , Rio de Janeiro , RJ , Brasil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Koifman
authors.affiliation: b Programa de Saúde Pública e Meio Ambiente - Escola Nacional de Saúde Pública - FIOCRUZ , Rio de Janeiro , RJ , Brasil.|e Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste , Rio de Janeiro , RJ , Brasil.
authors.forename: Jamila Alessandra
authors.initials: JA
authors.lastname: Perini
authors.affiliation: a Coordenação de Pesquisa, Instituto Nacional do Câncer , Rio de Janeiro , RJ , Brasil.|b Programa de Saúde Pública e Meio Ambiente - Escola Nacional de Saúde Pública - FIOCRUZ , Rio de Janeiro , RJ , Brasil.|d Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro , Rio de Janeiro , RJ , Brasil.
authors.forename: Rosane
authors.initials: R
authors.lastname: Vianna-Jorge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D055815:Young Adult
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; VEGFA; breast cancer; disease-free survival; haplotypes; polymorphisms; prognostic factors