PMID- 11241233 OWN - NLM STAT- MEDLINE DCOM- 20010419 LR - 20190620 IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 91 IP - 4 DP - 2001 Feb 15 TI - Genetic variation in the tumor necrosis factor-alpha promoter region and in the stress protein hsp70-2: susceptibility and prognostic implications in breast carcinoma. PG - 672-8 AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha 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-alpha and hsp70-2 may represent not only markers for the increased risk of breast carcinoma but also may predict the clinical outcome. CI - Copyright 2001 American Cancer Society. FAU - Mestiri, S AU - Mestiri S AD - Laboratoire d'Immuno-Oncologie Moleculaire, Faculte de Medecine de Monastir, Universite du Centre, 5019 Monastir, Tunisia. FAU - Bouaouina, N AU - Bouaouina N FAU - Ahmed, S B AU - Ahmed SB FAU - Khedhaier, A AU - Khedhaier A FAU - Jrad, B B AU - Jrad BB FAU - Remadi, S AU - Remadi S FAU - Chouchane, L AU - Chouchane L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Breast Neoplasms/*genetics/mortality/therapy MH - Breast Neoplasms, Male/genetics/mortality/therapy MH - Female MH - Genotype MH - HSP70 Heat-Shock Proteins/*genetics MH - Humans MH - Male MH - Middle Aged MH - Multivariate Analysis MH - *Polymorphism, Genetic MH - Prognosis MH - Risk Factors MH - Survival Analysis MH - Tumor Necrosis Factor-alpha/*genetics EDAT- 2001/03/10 10:00 MHDA- 2001/04/21 10:01 CRDT- 2001/03/10 10:00 PHST- 2001/03/10 10:00 [pubmed] PHST- 2001/04/21 10:01 [medline] PHST- 2001/03/10 10:00 [entrez] AID - 10.1002/1097-0142(20010215)91:4<672::AID-CNCR1050>3.0.CO;2-J [pii] AID - 10.1002/1097-0142(20010215)91:4<672::aid-cncr1050>3.0.co;2-j [doi] PST - ppublish SO - Cancer. 2001 Feb 15;91(4):672-8. doi: 10.1002/1097-0142(20010215)91:4<672::aid-cncr1050>3.0.co;2-j.