@Article{,
AUTHOR = {Kaouther Snoussi, A. Donny Strosberg, Noureddine Bouaouina, Slim Ben Ahmed, Lotfi Chouchane},
TITLE = {Genetic variation in pro-inflammatory cytokines (interleukin-1β, interleukin-1a and interleukin-6) associated with the aggressive forms, survival, and relapse prediction of breast carcinoma},
JOURNAL = {European Cytokine Network},
VOLUME = {16},
YEAR = {2005},
NUMBER = {4},
PAGES = {253--260},
URL = {http://www.techscience.com/ECN/v16n4/66201},
ISSN = {1952-4005},
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.},
DOI = {}
}