The Influence of CYP3A4 Polymorphism in Sex Steroids as a Risk Factor for Breast Cancer

Abstract

Objective Epidemiological studies have shown evidence of the effect of sex hormones in the pathogenesis of breast cancer, and have suggested a relationship of the disease with variations in genes involved in estrogen synthesis and/or metabolism. The aim of the present study was to evaluate the association between the CYP3A4*1B gene polymorphism (rs2740574) and the risk of developing breast cancer.

Methods In the present case-control study, the frequency of the CYP3A4*1B gene polymorphism was determined in 148 women with breast cancer and in 245 women without the disease. The DNA of the participants was extracted from plasma samples, and the gene was amplified by polymerase chain reaction. The presence of the polymorphism was determined using restriction enzymes.

Results After adjusting for confounding variables, we have found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio = 1.151; 95% confidence interval: 0.714–1.856; p = 0.564). We have also found no association with the presence of hormone receptors, with human epidermal growth factor receptor 2 (HER2) overexpression, or with the rate of tumor cell proliferation.

Conclusion We have not observed a relationship between the CYP3A4*1B gene polymorphism and the occurrence of breast cancer.

Resumo

Objetivo Estudos epidemiológicos têm mostrado evidências da influência dos hormônios sexuais na patogênese do câncer de mama, e têm sugerido uma relação entre a doença e variações em genes envolvidos na síntese e/ou metabolização de estrógenos. O objetivo do presente estudo foi avaliar a associação entre o polimorfismo do gene CYP3A4*1B (rs2740574) e o risco de desenvolvimento da neoplasia mamária.

Métodos No presente estudo de caso-controle, a frequência de polimorfismo do gene CYP3A4*1B foi determinada em 148 mulheres com câncer de mama, e em 245 mulheres sem a doença. O DNA das participantes foi extraído do plasma, e o gene foi amplificado por meio de reação em cadeia da polimerase, enquanto o polimorfismo foi determinado por enzimas de restrição.

Resultados O polimorfismo, após o ajuste para variáveis de confusão, não foi associado à ocorrência de câncer de mama (razão de possibilidades = 1,151; intervalo de confiança de 95%: 0,714–1,856; p = 0,564). Também não observamos associação com a presença de receptores hormonais, superexpressão do receptor tipo 2 do fator de crescimento epidérmico humano (HER2, na sigla em inglês), ou com a taxa de proliferação celular do tumor.

Conclusão Não observamos relação entre o polimorfismo do gene CYP3A4*1B e a ocorrência de câncer de mama.

Keywords

Cyp3a4 - breast cancer - polymorphism - estrogens - genetics

Palavras-chave

CYP3A4 - câncer de mama - polimorfismo - estrógenos - genética

Contributors

Veiga MG, Felizi RT, Reis DG, Carelli Filho I, Fernandes CE, Souto RP and Oliveira E contributed with the project and the interpretation of data, the writing of the article, the critical review of the intellectual content, and the final approval of the version to be published.

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