Association between matrix metallopeptidase 9 polymorphism and breast cancer risk / Associação entre o polimorfismo do gene metalopeptidase de matriz 9 e o risco de câncer de mama

Abstract Objective Epidemiological studies have shown evidence of the effect of genetic variations in the pathogenesis of breast cancer and have suggested a relationship of the disease with genetic polymorphisms. Matrix metallopeptidase 9 (MMP-9) is a collagenase responsible for the degradation of type IV collagen, the major component of the basement membrane, and other essential extra cellular matrix components, being involved in the tumor cell invasion and metastasis. Our objective was to evaluate the relationship between the MMP-9-1562 C/T polymorphism (rs 3918242) and the risk of developing breast cancer. Methods In this case-control study, the frequency of the MMP-9-1562 C/T polymorphism (rs 3918242) was determined in 148 women with breast cancer and 245 women without the disease. The DNA was extracted from plasma samples, and the gene was amplified by polymerase chain reaction (PCR); the presence of the polymorphism was determined using restriction enzymes. Results After adjusting for confounding variables, we found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio [OR] = 1.159, 95% confidence interval [CI]: 0.6625-1.997, p = 0.5964). We also found no association with more advanced disease, the presence of hormone receptors, human epidermal growth factor receptor 2 (HER2) overexpression, or rate of tumor cell proliferation. Conclusion We did not observe a relationship between MMP-9-1562 C/T polymorphism (rs 3918242) and the occurrence of breast cancer.

Resumo Objetivo Estudos epidemiológicos vêm demonstrando evidências da influência de variações genéticas na patogênese do câncer de mama, e têm sugerido associação de polimorfismos comuma maior susceptibilidade à doença. A metalopeptidase dematriz 9 (MMP-9) é uma colagenase responsável pela degradação do colágeno tipo IV, omaior componente da membrana basal, e outros componentes essenciais da matriz extra celular, estando envolvido na invasão da célula tumoral emetástase. Nosso objetivo foi avaliar a associação entre o polimorfismo da 1562 C/T (rs 3918242) do gene MMP-9 e o desenvolvimento da neoplasia mamária. Métodos Neste estudo caso-controle, a frequência de polimorfismo 1562 C/T (rs 3918242) do MMP-9 foi determinada em 148 mulheres com câncer de mama e 245 mulheres sem a doença. O DNA foi extraído do plasma e o gene foi amplificado por meio de reação em cadeia da polimerase (RCP). O polimorfismo foi determinado por enzimas de restrição. Resultados O polimorfismo, após o ajuste para variáveis confundidoras, não foi associado coma ocorrência de câncer de mama (razão de possibilidade [RP] = 1,159, intervalo de confiança de 95% [IC95]: 0,6625-1,997, p = 0,5964). Também não foi demonstrado associação comestadiamentos mais avançados, presença de receptores hormonais, superexpressão de HER2 e tampouco com a taxa de proliferação celular do tumor. Conclusão Não observamos relação entre o polimorfismo 1562 C/T (rs 3918242) do gene MMP-9 e a ocorrência de câncer de mama.

Marcadores de inflamación endotelial subclínica en una familia con hiperaldosteronismo familiar tipo I por mutación de novo / Subclinical endothelial inflammation markers in a family with type I familial hyperaldosteronism caused by a de novo mutation

Background: Type I familial hyperaldosteronism is caused by the presence of a chimaetic gene CYPl 1B1/CYP11BZ which encodes an enzyme with aldosterone synthetase activityregulated by adrenocorticotrophic hormone (ACTH). Therefore, in patients with FH I is possible to normalize the aldosterone levels with glucocorticoid treatment. Recently it has been shown that aldosterone plays a role in the production of endothelial oxidative stress and subclinical inflammation. Aim: To evaluate subclinical endothelial inflammation markers, Me Metalloproteinase 9 (MMP-9) and ultrasensitive C reactive protein (usPCR), before and after glucocorticoid treatment in family members with FH-I caused by a de novo mutation. Patients and methods: We report three subjects with FH-I in a single family (proband, father and sister). We confirmed the presence of a chimaeric CYPl 1B1/CYP11B2 gene by ¡ong-PCR in all of them. Paternal grandparents were unaffected by the mutation. The proband was a 13year-old boy with hypertension stage 2 (in agree to The JointNational Committee VII, JNC-vIl), with an aldosterone/plasma rennin activity ratio equal to 161. A DNA paternity test confirmed the parental relationship between the grandparents and father with the index case. MMP-9 and usPCR levels were determined by gelatin zymography and nephelometry, respectively. Results: All affected subjects had approximately a 50 percent increase in MMP-9 levels. Only the father had an elevated usPCR. The endothelial inflammation markers returned to normal range after glucocorticoid treatment. Conclusions: We report a family canying a FH-I caused by a de novo mutation. The elevation of endothelial inflammation markers in these patients and its normalization after glucocorticoid treatment provides new insight about the possible deleterious effect of aldosterone on the endothelium.