RESUMEN
Vitamin D Receptor (VDR), a nuclear steroid receptor, is a transcription factor with a primary physiologic role in calcium metabolism. It has also a physiologic role in breast tissues during development of the gland and postpartum. In addition, it is commonly expressed in breast cancer and has tumor suppressive effects. Cytochrome enzymes CYP27B1 and CYP24A1 that perform the final conversion of the circulating form of vitamin D, 25-hydroxyvitamin D (25-OHD) to the active VDR ligand, 1a,25-dihydroxyvitamin D and the catabolism of it to inactive 24,25-dihydroxyvitamin D, respectively, are also expressed in breast cancer tissues. Defective regulation of the receptor and the metabolic enzymes of VDR ligand is prevalent in breast cancer and leads to decreased VDR signaling. The expression and molecular defects of VDR, CYP27B1 and CYP24A1 that perturb physiologic function, the implications for breast cancer progression and therapeutic opportunities are discussed in this paper.
Asunto(s)
25-Hidroxivitamina D3 1-alfa-Hidroxilasa/fisiología , Neoplasias de la Mama/metabolismo , Receptores de Calcitriol/fisiología , Vitamina D3 24-Hidroxilasa/fisiología , Animales , Mama/metabolismo , Mama/patología , Línea Celular Tumoral , Femenino , Regulación de la Expresión Génica , Humanos , Vitamina D/análogos & derivados , Vitamina D/metabolismoRESUMEN
BACKGROUND: Single-nucleotide polymorphisms (SNPs) are important indicators of susceptibility to breast cancer. OBJECTIVE: To assess the associations between SNPs in the FAM13A, PHLDB1, and CYP24A1 gene and breast cancer risk in the Chinese Han population. METHODS: We performed a case-control study including 379 female breast cancer patients and 407 female healthy controls. The three SNPs were genotyped using Agena MassARRAY platform. The χ2 test was used to compare alleles and genotypes frequencies of polymorphisms between case and control groups. Genetic models analyses to assess the associations between SNPs and breast cancer risk by computing odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RegulomeDB and HaploReg databases were used to calculate possible functional effects of polymorphisms. RESULTS: Overall analysis results showed that rs4809957 was associated with an increased risk of breast cancer (allele A: OR = 1.27, 95% CI: 1.03-1.55, p = 0.024; AA vs. GG: OR = 1.80, 95% CI: 1.15-2.82, p = 0.010; recessive model: OR = 1.70, 95% CI: 1.12-2.58, p = 0.012); and rs1059122 was found to be associated with a reduced breast cancer risk in the recessive model (OR = 0.71, 95% CI: 0.51-0.98, p = 0.039). Stratification analysis found significant associations between the three SNPs (rs1059122, rs17748, and rs4809957) and breast cancer risk. CONCLUSION: Our results suggested that rs1059122 (FAM13A), rs17748 (PHLDB1), and rs4809957 (CYP24A1) might contribute to breast cancer susceptibility in the Chinese Han population. Future studies with large samples are required to confirm our findings, as well as functional studies are needed to explore their function in the breast cancer development.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas Activadoras de GTPasa/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de Neoplasias/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Vitamina D3 24-Hidroxilasa/genética , Adulto , Alelos , Pueblo Asiatico/genética , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Femenino , Proteínas Activadoras de GTPasa/fisiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular/fisiología , Menopausia , Persona de Mediana Edad , Modelos Genéticos , Anotación de Secuencia Molecular , Proteínas de Neoplasias/fisiología , Estadificación de Neoplasias , Proteínas del Tejido Nervioso/fisiología , Riesgo , Carga Tumoral , Vitamina D3 24-Hidroxilasa/fisiologíaRESUMEN
CYP24A1 plays important roles in antiproliferative effects, which have been proved in many human tumor cells. Polymorphisms in CYP24A1 may affect the risk of lung cancer, but the results remained inconclusive. To enhance the understanding of possible relationship between CYP24A1 polymorphism rs6068816 and lung cancer risks, we first carried out this case-control study among Chinese female nonsmokers, including 345 lung cancer patients and 351 noncancer controls. Our results revealed that individuals carrying CT and CC genotype were associated with decreasing lung cancer risk (adjusted odds ratios were 0.71 and 0.59, and 95% confidence intervals were 0.52-0.97 and 0.35-0.99, p-values were 0.031 and 0.048, respectively). Patients carrying allele-T showed lower hazard risks, especially in adenocarcinoma and advanced stage cancers. We also found that subjects with allele-T showed a relatively low risk of lung cancer when they were exposed to oil fume. But neither additive scale nor multiplicative scale revealed interactions between allele-T and environmental exposures, including oil fume, coal fuel fume, and passive smoking. Overall, these findings indicated that CYP24A1 polymorphism rs6068816 could be significantly associated with susceptibility of lung cancer in Chinese female nonsmokers.