ABSTRACT
BACKGROUND: The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D3 (circulating form) and 1,25(OH)2D3 (active form), in colorectal cancer (CRC) patients. METHODS: One hundred fifty-two CRC patients and 321 controls were included. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by PCR-RFLP. Those of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing. RESULTS: The median serum levels of circulating vitamin D were not different between CRC patients and controls; however, the percentage of those with deficient vitamin D was higher in patients with cancer. The active form of the vitamin D was higher in CRC patients. VDR, CYP27B1 and CYP24A1 polymorphic genotypes had no influence on serum levels of circulating vitamin D. The correlation between circulating and active vitamin D forms was lower among patients with CRC, regardless of the presence or absence of any genetic polymorphism. The mean serum levels of active vitamin D were higher among patients with polymorphic genotype variants of Apa1 or Bsm1. CONCLUSIONS: CRC patients had a higher frequence of insufficient vitamin D and a higher concentration of active vitamin D. These concentration were higher between patients with polymorphic genotypes variants of ApaI and BsmI, CYP24A1 and CYP27B1. Polymorphic genotypes cause a lower correlation between the forms of vitamin D.
Subject(s)
Colorectal Neoplasms/blood , Cytochrome P450 Family 27/genetics , Receptors, Calcitriol/genetics , Vitamin D3 24-Hydroxylase/genetics , Vitamin D/blood , Aged , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Middle Aged , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Vitamin D/geneticsABSTRACT
BACKGROUND: The aim of this study was to evaluate the association between adiponectin and tumor necrosis factor-α;ï (TNF-α;) serum levels in colorectal cancer (CRC) patients and compare these levels to clinical stage and nutritional status. METHODS: A total of 79 patients were enrolled in the study (39 with CRC and 40 in the control). Nutritional status was assessed by Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), and phase angle (PhA). Adiponectin and TNF-α;ï serum concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS: Serum adiponectin levels were higher among CRC patients (p = 0.001). TNF-α;ï serum levels were not significantly different between the groups, but patients with stage III or IV CRC had higher levels of TNF-α;ï than those with lower stage disease (p = 0.037). The three tools used for the assessment of nutritional status (BMI, PhA, and PG-SGA) demonstrated that patients with a more severe nutritional deficit had higher adipocytokine levels, although these differences were significant only to TNF- ï¡, when distributed PhA in tertiles. CONCLUSIONS: Adiponectin levels were higher among CRC patients. Although TNF-α;ï serum levels from CRC patients did not differ significantly to the control group, CRC patients with stage III or IV had higher levels compared to those with stage I and II tumors. Nutritional status, as determined by BMI, PhA, and PG-SGA, demonstrated that patients with a greatest nutritional deficit, had higher levels of adipocytokines; however, these differences were significant only for TNF-ï¡, when distributed PhA in tertiles.
ANTECEDENTES: El propósito de este estudio fue evaluar la asociación entre las concentraciones séricas de adiponectina y de factor de necrosis tumoral-ï¡ï (TNF-ï¡) en paciente con cáncer colorrectal (CCR) y comparar estas concentraciones con el estadio clínico y el estado nutritivo. MÉTODOS: Se reclutó a un total de 79 pacientes en el estudio (39 con CCR y 40 en el grupo control). Se evaluó el estado nutritivo mediante la Evaluación Global Subjetiva Generada por el Paciente (PG-SGA), el índice de masa corporal (IMC) y el ángulo de fase (AF). Se determinaron las concentraciones séricas de adiponectina y de TNF-ï¡ï mediante un inmunoensayo de absorción ligado a enzima. RESULTADOS: Las concentraciones séricas de adiponectina fueron superiores en los pacientes con CCR (p = 0,001). Las concentraciones séricas de TNF-ï¡ï no fueron significativamente distintas entre los grupos pero los pacientes con CC en estadios III o IV tuvieron mayores concentraciones de TNF-ï¡ï que aquellos con un menor estadio de la enfermedad (p = 0,037). Las tres herramientas empleadas para evaluar el estado nutritivo (IMC, AF y PGSGA) demostraron que los pacientes con un déficit nutricional más pronunciado presentaban mayores concentraciones de adipocitocina, aunque algunas diferencias sólo fueron significativas para el TNF-ï¡ï cuanto se distribuyó el AF en terciles. CONCLUSIONES: Las concentraciones de adiponectina fueron superiores en pacientes con CCR. Aunque las concentraciones séricas de TNF-ï¡ï de los pacientes con CCR no diferían significativamente de las del grupo control, los pacientes con CCR en estadios III o IV tuvieron concentraciones superiores en comparación con aquellos con tumores en estadios I y II. El estado nutritivo, determinado por IMC, AF y PG-SGA, demostró que los pacientes con un mayor déficit nutricional tenían concentraciones superiores de adipocitocinas; sin embargo, estas diferencias sólo fueron significativas para el TNF-ï¡ï cuando el AF se distribuyó en terciles.
