Genetic variation in the tumor necrosis factor-α promoter region and in the stress protein hsp70-2: Susceptibility and prognostic implications in breast carcinoma

Souhir Mestiri, Noureddine Bouaouina, Slim Ben Ahmed, Achraf Khedhaier, Besma Belhadj Jrad, Sami Remadi, Lotfi Chouchane

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Abstract

BACKGROUND. Tumor necrosis factor-α (TNF-α) and stress proteins (heat shock proteins) are determining factors in the immune response to tumor cells. The authors designated a large study to investigate the susceptibility and prognostic implications of the genetic variation in TNF-α and hsp70-2 in breast carcinoma. METHODS. The authors used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-α promoter region and that of the hsp70-2 gene in 243 unrelated Tunisian patients with breast carcinoma and 174 healthy control subjects. Associations of the clinicopathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival and the disease free survival (DFS) were assessed using univariate and multivariate analyses. RESULTS. A highly significant association was found between TNF2 homozygous genotype and breast carcinoma (relative risk [RR], 4.44; P = 0.006). A high relative risk of breast carcinoma was found to be associated with one hsp70-2 homozygous genotype (P2/P2; RR, 7.12; P = 0.0001). The TNF2 homozygous genotype showed a significant association with reduced DFS and/or overall survival by univariate test. Conversely, P2-hsp70-2 homozygous genotype associated with increased overall survival but not with DFS. Multivariate analysis retained significance for TNF2 homozygous genotype as an independent prognostic indicator for both DFS (RR, 2.75; P = 0.01) and overall survival (RR, 4.08; P = 0.01). CONCLUSIONS. Genetic variation in TNF-α and hsp70-2 may represent not only markers for the increased risk of breast carcinoma but also may predict the clinical outcome.

Original languageEnglish
Pages (from-to)672-678
Number of pages7
JournalCancer
Volume91
Issue number4
DOIs
Publication statusPublished - 15 Feb 2001

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Keywords

  • Breast carcinoma
  • Polymorphism
  • Prognosis
  • Stress proteins
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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