Genetic variation in pro-inflammatory cytokines (interleukin-1β, interleukin-1α and interleukin-6) associated with the aggressive forms, survival, and relapse prediction of breast carcinoma

Kaouther Snoussi, A. Donny Strosberg, Noureddine Bouaouina, Slim Ben Ahmed, Lotfi Chouchane

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Objectives. Interleukin-1 (IL-1) and interleukin-6 (IL-6) are determining factors in the immune and inflammatory responses to tumors cells. Experimental data suggest that interleukin-1 and interleukin-6 play important roles in the development and progression of breast cancer. We designed a broad study to investigate the susceptibility and prognostic implications of the genetic variation in IL-1α, IL-1β and IL-6 in breast carcinoma. Experimental design. We used the polymerase chain reaction and restriction enzyme digestion to characterize the genetic variation of IL-1α, IL-1β and IL-6 in 305, unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations between the genetic markers and the clinicopathological parameters, the specific overall survival rate (OVS) of breast carcinoma and the disease free-survival rate (DFS) were assessed using univariate and multivariate analyses. Results. Both IL-6 (-597) GA and IL-6 (-174) GC heterozygous genotypes were found to be significantly associated with breast carcinoma (OR = 1.59, p = 0.024 and OR = 1.61, p = 0.022 respectively). A highly significant association was found between the (+3954) T allele of IL1-B gene and the aggressive phenotype of breast carcinoma as defined by the high histological grade, axillary lymph node metastasis and large tumor size. The IL-1α (-889) TT homozygous genotype showed a significant association with reduced disease-free survival and/or overall survival rate. The IL-1β (+3954) TT, IL-6 (-597) GG and IL-6 (-174) GG homozygous genotypes were found to be associated with reduced DFS but not with overall survival. Conclusions. The polymorphisms in the promoter region of the IL-6 gene may represent a marker for the increased risk of breast carcinoma. Genetic variations in IL-1α, IL-1β and IL-6 may predict the clinical outcome of breast carcinoma.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalEuropean Cytokine Network
Volume16
Issue number4
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Interleukin-1
Interleukin-6
Breast Neoplasms
Cytokines
Recurrence
Survival
Survival Rate
Disease-Free Survival
Genotype
Tumors
Genes
Breast Diseases
Polymerase chain reaction
Immunologic Factors
Polymorphism
Genetic Markers
Genetic Promoter Regions
Design of experiments
Digestion
Neoplasms

Keywords

  • Breast carcinoma
  • Interleukin- 1α
  • Interleukin-1β
  • Interleukin-6
  • Polymorphism
  • Prognosis
  • Susceptibility

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry

Cite this

Genetic variation in pro-inflammatory cytokines (interleukin-1β, interleukin-1α and interleukin-6) associated with the aggressive forms, survival, and relapse prediction of breast carcinoma. / Snoussi, Kaouther; Strosberg, A. Donny; Bouaouina, Noureddine; Ahmed, Slim Ben; Chouchane, Lotfi.

In: European Cytokine Network, Vol. 16, No. 4, 2005, p. 253-260.

Research output: Contribution to journalArticle

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abstract = "Objectives. Interleukin-1 (IL-1) and interleukin-6 (IL-6) are determining factors in the immune and inflammatory responses to tumors cells. Experimental data suggest that interleukin-1 and interleukin-6 play important roles in the development and progression of breast cancer. We designed a broad study to investigate the susceptibility and prognostic implications of the genetic variation in IL-1α, IL-1β and IL-6 in breast carcinoma. Experimental design. We used the polymerase chain reaction and restriction enzyme digestion to characterize the genetic variation of IL-1α, IL-1β and IL-6 in 305, unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations between the genetic markers and the clinicopathological parameters, the specific overall survival rate (OVS) of breast carcinoma and the disease free-survival rate (DFS) were assessed using univariate and multivariate analyses. Results. Both IL-6 (-597) GA and IL-6 (-174) GC heterozygous genotypes were found to be significantly associated with breast carcinoma (OR = 1.59, p = 0.024 and OR = 1.61, p = 0.022 respectively). A highly significant association was found between the (+3954) T allele of IL1-B gene and the aggressive phenotype of breast carcinoma as defined by the high histological grade, axillary lymph node metastasis and large tumor size. The IL-1α (-889) TT homozygous genotype showed a significant association with reduced disease-free survival and/or overall survival rate. The IL-1β (+3954) TT, IL-6 (-597) GG and IL-6 (-174) GG homozygous genotypes were found to be associated with reduced DFS but not with overall survival. Conclusions. The polymorphisms in the promoter region of the IL-6 gene may represent a marker for the increased risk of breast carcinoma. Genetic variations in IL-1α, IL-1β and IL-6 may predict the clinical outcome of breast carcinoma.",
keywords = "Breast carcinoma, Interleukin- 1α, Interleukin-1β, Interleukin-6, Polymorphism, Prognosis, Susceptibility",
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T1 - Genetic variation in pro-inflammatory cytokines (interleukin-1β, interleukin-1α and interleukin-6) associated with the aggressive forms, survival, and relapse prediction of breast carcinoma

AU - Snoussi, Kaouther

AU - Strosberg, A. Donny

AU - Bouaouina, Noureddine

AU - Ahmed, Slim Ben

AU - Chouchane, Lotfi

PY - 2005

Y1 - 2005

N2 - Objectives. Interleukin-1 (IL-1) and interleukin-6 (IL-6) are determining factors in the immune and inflammatory responses to tumors cells. Experimental data suggest that interleukin-1 and interleukin-6 play important roles in the development and progression of breast cancer. We designed a broad study to investigate the susceptibility and prognostic implications of the genetic variation in IL-1α, IL-1β and IL-6 in breast carcinoma. Experimental design. We used the polymerase chain reaction and restriction enzyme digestion to characterize the genetic variation of IL-1α, IL-1β and IL-6 in 305, unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations between the genetic markers and the clinicopathological parameters, the specific overall survival rate (OVS) of breast carcinoma and the disease free-survival rate (DFS) were assessed using univariate and multivariate analyses. Results. Both IL-6 (-597) GA and IL-6 (-174) GC heterozygous genotypes were found to be significantly associated with breast carcinoma (OR = 1.59, p = 0.024 and OR = 1.61, p = 0.022 respectively). A highly significant association was found between the (+3954) T allele of IL1-B gene and the aggressive phenotype of breast carcinoma as defined by the high histological grade, axillary lymph node metastasis and large tumor size. The IL-1α (-889) TT homozygous genotype showed a significant association with reduced disease-free survival and/or overall survival rate. The IL-1β (+3954) TT, IL-6 (-597) GG and IL-6 (-174) GG homozygous genotypes were found to be associated with reduced DFS but not with overall survival. Conclusions. The polymorphisms in the promoter region of the IL-6 gene may represent a marker for the increased risk of breast carcinoma. Genetic variations in IL-1α, IL-1β and IL-6 may predict the clinical outcome of breast carcinoma.

AB - Objectives. Interleukin-1 (IL-1) and interleukin-6 (IL-6) are determining factors in the immune and inflammatory responses to tumors cells. Experimental data suggest that interleukin-1 and interleukin-6 play important roles in the development and progression of breast cancer. We designed a broad study to investigate the susceptibility and prognostic implications of the genetic variation in IL-1α, IL-1β and IL-6 in breast carcinoma. Experimental design. We used the polymerase chain reaction and restriction enzyme digestion to characterize the genetic variation of IL-1α, IL-1β and IL-6 in 305, unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations between the genetic markers and the clinicopathological parameters, the specific overall survival rate (OVS) of breast carcinoma and the disease free-survival rate (DFS) were assessed using univariate and multivariate analyses. Results. Both IL-6 (-597) GA and IL-6 (-174) GC heterozygous genotypes were found to be significantly associated with breast carcinoma (OR = 1.59, p = 0.024 and OR = 1.61, p = 0.022 respectively). A highly significant association was found between the (+3954) T allele of IL1-B gene and the aggressive phenotype of breast carcinoma as defined by the high histological grade, axillary lymph node metastasis and large tumor size. The IL-1α (-889) TT homozygous genotype showed a significant association with reduced disease-free survival and/or overall survival rate. The IL-1β (+3954) TT, IL-6 (-597) GG and IL-6 (-174) GG homozygous genotypes were found to be associated with reduced DFS but not with overall survival. Conclusions. The polymorphisms in the promoter region of the IL-6 gene may represent a marker for the increased risk of breast carcinoma. Genetic variations in IL-1α, IL-1β and IL-6 may predict the clinical outcome of breast carcinoma.

KW - Breast carcinoma

KW - Interleukin- 1α

KW - Interleukin-1β

KW - Interleukin-6

KW - Polymorphism

KW - Prognosis

KW - Susceptibility

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