RESUMO
BACKGROUND: Polymorphism of the genes of Human Epidermal growth factor receptor1 (HER1) and receptor2 (HER2) have been reported to be linked to pathogenesis of several malignant tumors but still there is contradiction regarding their association with breast cancer. OBJECTIVE: In this case control study we aimed to analyze the frequency of HER1 R497K (rs 11543848) and HER2 I655V (rs 1136201) Polymorphisms in breast cancer. SUBJECT AND METHOD: The frequency of HER1 Arg(R) 497Lys (K) and HER2 Ile (I) 655Val (V) polymorphisms were tested in 64 breast cancer patients and 86 normal control by polymerase chain reaction followed by restriction fragment polymorphism detection. Immunohistochemical analysis was done for HER2 protein on the available 18 malignant tissue samples. RESULTS: HER1 497K and HER2 655V variant had significantly increased breast cancer risk (OR=2.6, 95% CI 1.6-4.2, OR=2.2, 95% CI 1.2-4.1, p< 0.05) respectively. Moreover, combined HER1 K497 and HER2 V655 variant was detected in 26.6% malignant in comparison to 8.14% of control group (OR=4.1, 95% CI 1.58-10.57), but, no significant association was noticed between both Polymorphisms and clinicopathological features of the disease. As regard HER2 immunohistochemical expression no significant correlation was revealed with HER2 655V polymorphism. CONCLUSIONS: our findings suggest that HER1 497K and HER2 655V polymorphisms are potential risk factor for development of breast cancer.
Assuntos
Neoplasias da Mama/genética , Carcinoma/genética , Receptores ErbB/genética , Polimorfismo de Nucleotídeo Único , Receptor ErbB-2/genética , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Estudos de Casos e Controles , Receptores ErbB/metabolismo , Feminino , Fibroadenoma/genética , Fibroadenoma/metabolismo , Frequência do Gene , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Polimorfismo de Fragmento de Restrição , Receptor ErbB-2/metabolismo , Fatores de RiscoRESUMO
BACKGROUND: Lead toxicity has been subjected to intensive research work, but some aspects of its mechanism needs to be elucidated. OBJECTIVES: In the current study we aim to investigate the impact of lead toxicity on some different intermediates of apoptotic signaling pathway in experimental rats. DESIGN AND METHODS: We measured caspase-8 and caspase-9 [by chemilumenescence], Bax and Bcl-2 [by ELISA] in Experimental rats, injected intraperitoneally with lead acetate for 7days at the dosage of 25, 50 and l00 mg/kg body weight and compared to control rats injected with deionized distilled water instead. instead. RESULTS: Lead acetate significantly increased the levels of caspase 8, caspase 9 and Bax in liver, kidney and brain of experimental animals especially those with high doses. Meanwhile, caspase 8 and Bax significantly increased in brain tissue at low dose of lead, while Bcl-2 significantly increased only with advanced toxicity. Furthermore, Bax/bcl2 ratio was significantly high in kidney (p<0.05), liver (p<0.01) and brain (p<0.01) at higher doses of lead toxicity. However, brain tissues showed significant Bax/Bcl2 ratio (p<0.05) at low lead dose. A significant positive correlation was noticed between the blood level of lead and enzymatic level of caspase 8, caspase 9 and Bax in different tissues. CONCLUSION: : we concluded that lead might have toxic effect through intrinsic and extrinsic induction of apoptotic pathway with prominent effect on brain tissue even at low dose.
