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
Author(s) : Kaouther Snoussi, A Donny Strosberg, Noureddine Bouaouina, Slim Ben Ahmed, Lotfi Chouchane , Laboratoire d’Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Université de Monastir, 5019 Monastir, Tunisia, Department of Infectology, Scripps-Florida USA, Department of Cancérologie Radiothérapie CHU Farhat Hached, Sousse, Tunisia, Service de Carcinologie Médicale, CHU Farhat Hached, Sousse, Tunisia.
Summary : 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, polymorphism, prognosis, susceptibility, interleukin-1α, interleukin-1β\;, interleukin-6
Pictures
Figure 1 Breast carcinoma specific overall survival
(A) and specific disease-free survival (B) of 305
breast carcinoma patients according to the presence or absence of
IL-1α (-889) TT homozygous genotypes (p denotes the log-rank test
value).
Figure 2 Breast carcinoma specific overall survival
(A) and specific disease-free survival (B) of 305
breast carcinoma patients according to the presence or absence of
IL-1β (+3954) TT homozygous genotypes (p denotes the log-rank test
value).
Figure 3 Breast carcinoma specific disease-free
survival of 305 breast carcinoma patients according to the presence
or absence of IL-6 (-174) GG (A) and IL-6 (-597) GG
(B) homozygous genotypes (p denotes the log-rank test
value).
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