RESUMEN
The MMP2 gene has been implicated in the pathogenesis of endometriosis. We investigated the role and function of single-nucleotide polymorphisms (SNP) of MMP2 in relation to endometriosis. First a case-control study was conducted and 17 SNPs were examined in 211 patients and 344 controls. Regression analysis was used to evaluate the genetic effect. We used reporter assay to validate the functional consequences of the significant SNP. Two SNPs (rs243832 and rs7201) had P-values <0.05 and they are in strong linkage disequilibrium (D'=0.96 and r(2)=0.47). Further analysis showed that rs7201 but not rs246832 was an independent risk factor and the risk C allele of rs7201 had an odds ratio (OR) of 1.88 (P=0.004). SNP rs7201 is located at the 3'-untranslated region and is predicted to be within the microRNA-520g binding site. The reporter assay for rs7201 showed that the risk C allele had a higher expression level than the A allele (P=0.027). Using microRNA-520g mimic and inhibitor, the results indicated that the A allele but not the risk C allele can be regulated by microRNA-520g. The C allele of SNP rs7201 increases a risk for endometriosis because of out of regulation by microRNA-520g.
Asunto(s)
Pueblo Asiatico , Endometriosis/genética , Predisposición Genética a la Enfermedad , Metaloproteinasa 2 de la Matriz/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , Endometriosis/etnología , Femenino , Genotipo , Humanos , Análisis de RegresiónRESUMEN
The objective of this study was to investigate whether somatic mutations in the mitochondrial DNA (mtDNA) D-loop region correlate with known prognostic factors, namely, age, tumor size, lymph node status, metastasis, tumor-node-metastasis stage, lymphovascular invasion, and status of the progesterone receptor, estrogen receptor, ERBB2 (alias HER2/neu), and TP53 proteins (as determined by immunohistochemistry) and to investigate their relationship, if any, to TP53 mutations in human breast cancer. Thirty breast tumors without BRCA mutation, along with adjacent nontumorous tissues, were genotyped for the mtDNA D-loop region and for the promoter as well as the coding region of the TP53 gene. Clinicopathological parameters were recorded and assessed. In all, 17 somatic mtDNA D-loop mutations were identified, in 13 of 30 tumor samples (43%); two mutations were novel: 544C>T and 16510A>C. Four TP53 mutations were found in six tumor samples (20%), and two (c.437G>A and c.706T>C) were novel. Only progesterone receptor status correlated with the number of somatic mtDNA D-loop mutations (likelihood chi-square test; P < 0.05). Somatic mutations in the mtDNA D-loop and in TP53 were independent of each other (Fisher's exact test; P > 0.05). These results suggest that the number of somatic mtDNA D-loop mutations may be an indicator of poor prognosis through a mechanism independent of TP53.
Asunto(s)
Neoplasias de la Mama/genética , Análisis Mutacional de ADN/métodos , ADN Mitocondrial/genética , Proteína p53 Supresora de Tumor/genética , Distribución de Chi-Cuadrado , Metilación de ADN , ADN Mitocondrial/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Mutación , Pronóstico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The association of Hispanic race/ethnicity and poverty with general survival time and breast cancer survival time was examined for a total of 14,896 breast cancer patients (14,035 White and 861 Hispanic) included in the National Cancer Institute Surveillance Epidemiology and End Results (NCI SEER) program in New Mexico and San Francisco between 1975 and 1984. Variables examined included: age, marital status, stage at diagnosis, tumor histology, delay, treatment, period of diagnosis (1975-79 vs. 1980-84), and poverty. Univariate analysis of 14,896 patients indicated that a greater proportion of Hispanics (vs. Whites) with breast cancer were: younger than age 50, married, diagnosed at a later stage, diagnosed in New Mexico, lived in greater poverty, were diagnosed between 1980-84, and died from breast cancer. Univariate Cox Proportion Hazards analysis indicated that poverty was a significant predictor for reduced general survival time. Being diagnosed in the 1980-84 period was a predictor for improved general survival time. Poverty and Hispanic race/ethnicity were significant predictors of reduced breast cancer survival time. Multivariate Cox Proportional Hazards models indicated that Hispanic race/ethnicity was a significant risk factor for breast cancer survival time for women aged 50 and older. For White women: state, marital status, poverty, surgery, radiation/hormonal treatments, and histology were significant risk factors for breast cancer survival time. For Hispanic women: stage, surgery, hormonal treatment and period of diagnosis were significant risk factors for breast cancer survival time. For White breast cancer patients, period of diagnosis was not a significant risk factor for reduced breast cancer survival time; but for Hispanics, it was a significant risk factor. In the age and race/ethnicity-stratified models of breast cancer survival time, similar risk factors emerged for both Whites and Hispanics. For both younger and older Hispanics, being diagnosed in the early 1980's (vs. the late 1970's) was associated with reduced breast cancer survival time--vs. Whites, who experienced no significant change in breast cancer survival time in the same time period. Poverty was not a predictor for Hispanic survival time in any of the models; however, it was a predictor for younger Whites for breast cancer survival time. These results fueled discussion in three areas targeting breast cancer in underserved women: the development of racial/ethnic-specific cancer control guidelines, the development of a breast cancer integrated delivery system, and population management