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1.
Ann N Y Acad Sci ; 1138: 84-94, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18837888

RESUMEN

Genetic alterations of the proto-oncogene human epidermal growth factor receptor (HER-2/neu) have been shown to induce malignant transformation and metastasis. Genotyping studies have addressed the association of codon 655 isoleucine to valine polymorphism located in the transmembrane coding region and the risk of breast cancer, but the results are inconsistent. In this study, we investigated the association of HER-2/neu Ile655Val polymorphism and the risk of breast cancer in a Sudanese population. In addition, the joint effects of HER-2/neu variants and our previously reported ESR1C325G polymorphism were tested for their association with breast cancer risk. Candidate single nucleotide polymorphism (SNP) in HER-2/neu Ile655Val [db SNP rs1136200] was genotyped in breast cancer patients and in healthy controls that were randomly selected from the same age group as the patients. Genotyping was performed using a high-throughput allelic discrimination method using real-time PCR, and data on clinical features and demographic details were collected. Associations between genotype and breast cancer were assessed by means of logistic regression. The prevalence of Val/Val genotype was similar in patients of breast cancer and control subjects. In comparison with the Ile/Ile genotype, the Ile/Val had a borderline significantly (P= 0.06) higher risk of breast cancer (OR = 2.95, 95% CI: 0.97-8.96). Regarding the genotypic and allelic frequencies stratified by age and menopausal status, there were no significant associations. A significantly higher risk of breast cancer was observed among homozygous carriers of ESR1325 CC genotype and heterozygous carriers of HER-2/neu655 Ile/Val genotype (P= 0.05; adjusted OR = 4.9, 95% CI: 1.0-24). The association of HER-2/neu Ile655Val polymorphism and the risk of breast cancer was borderline significant with the heterozygous carrier being at higher risk. However, the frequency of different polymorphic variants varies with ethnicity. The results of this study suggest that a significant gene-gene interaction between ESR1325C (previously reported) and HER-2/neu Ile655Val variants may jointly contribute to a higher risk of breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Genes erbB-2 , Predisposición Genética a la Enfermedad , Isoleucina/genética , Polimorfismo Genético , Valina/genética , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Proto-Oncogenes Mas , Factores de Riesgo
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