Genetic variation in IL-8 associated with increased risk and poor prognosis of breast carcinoma.

ABSTRACT

Interleukin-8 (IL-8), a potent chemoattractant, has been demonstrated to contribute to human cancer progression through its potential functions as a mitogenic, angiogenic, and motogenic factor. We designed a broad study to investigate whether genetic variation in IL-8 has implications for susceptibility to and prognosis in breast carcinoma. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 308 unrelated Tunisian patients with breast carcinoma and 236 healthy control subjects. Associations of the clinicopathologic parameters and the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. A significantly increased risk of breast carcinoma was associated with heterozygous IL-8 (-251) TA (OR=1.58, p=0.02) and homozygous IL-8 (-251) AA (OR=1.76, p=0.01) variants. A significant association between the IL-8 (-251) AA homozygous genotype and the aggressive phenotype of breast carcinoma as defined by the high histological grade, auxiliary's lymph node metastasis, and large tumor size was found. The IL-8 (-251) A allele manifested a significant association with decreased overall survival and disease-free survival for breast carcinoma patients. The polymorphism in the promoter region of the IL-8 gene may not only represent a marker for the increased risk of breast carcinoma but also predict the clinical outcome.