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Titolo:
Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus type 1 carriers
Autore:
Tsukasaki, K; Miller, CW; Kubota, T; Takeuchi, S; Fujimoto, T; Ikeda, S; Tomonaga, M; Koeffler, HP;
Indirizzi:
Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Dept Hematol,Mol Med Unit, Nagasaki 852, Japan Nagasaki Univ Nagasaki Japan 852 matol,Mol Med Unit, Nagasaki 852, Japan Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Div Hematol Oncol, Los Angeles, CA 90024 USA Univ Calif Los Angeles Los Angeles CA USA 90024 Los Angeles, CA 90024 USA Sasebo City Gen Hosp, Dept Hematol, Sasebo 8578511, Japan Sasebo City Gen Hosp Sasebo Japan 8578511 Hematol, Sasebo 8578511, Japan
Titolo Testata:
CANCER RESEARCH
fascicolo: 9, volume: 61, anno: 2001,
pagine: 3770 - 3774
SICI:
0008-5472(20010501)61:9<3770:TNFAPA>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
I HTLV-I; SYSTEMIC LUPUS-ERYTHEMATOSUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; FACTOR (TNF)-ALPHA GENE; NON-HODGKINS-LYMPHOMAS; 5'-FLANKING REGION; BCL-2; JAPAN; RISK; ATL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Tsukasaki, K Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Dept Hematol,Mol Med Unit, 1-12-4 Sakamoto, Nagasaki 852, Japan Nagasaki Univ 1-12-4 Sakamoto Nagasaki Japan 852 852, Japan
Citazione:
K. Tsukasaki et al., "Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia/lymphoma in human T-lymphotropic virus type 1 carriers", CANCER RES, 61(9), 2001, pp. 3770-3774

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) is etiologically associated with adult T-cell leukemia/lymphoma (ATL). Nevertheless, most individuals infected with HTLV-1 do not develop ATL. To attempt to identify genetic factorspromoting the progression to ATL, we investigated in HTLV-1 carriers the relationship between susceptibility to ATL and several polymorphisms: the three "decreased-detoxifying" polymorphisms in GSTM1, GSTT1, and CYP1A1, the "proapoptotic" polymorphism in BCL2, and the five "high-production" polymorphisms in tumor necrosis factor alpha (TNF-alpha) using PCR-based genotyping assays. ATL patients (n = 71) were younger than HTLV-1 carriers (n = 80; 57 +/- 12 versus 63 +/- 10 years; P = 0.0017), Male:female ratio in ATL patients was higher than in carriers (52:19 versus 19:61, respectively; P < 0.0001), probably reflecting a higher incidence of HTLV-1 infection in females and a higher incidence of development of ATL in males. We found that the frequency of the TNF-<alpha>-857T allele, reported to be associated with high transcriptional activity of the promoter/enhancer region of the TNF-alpha gene, was enriched in individuals with ATL compared with healthy carriers(18.3% versus 8.8%, respectively; odds ratio, 2.34; 95% confidence interval, 1.2-4.7). None of the other four TNF-alpha polymorphisms was a significant indicator of risk of development of ATL, although odds ratios (ATL versus carrier) of all of the TNF-alpha polymorphisms were higher than 1.0. Furthermore, analysis of polymorphisms for GSTM1, GSTT1, CYP1A1, and BCL2 showed no significant difference between ATL patients and healthy carriers. Genetic polymorphism leading to increased TNF-a production may enhance susceptibility to ATL among HTLV-1 carriers. Alternatively, but less likely, the HLA loci might be an important factor because the TNF-alpha gene lies within the class III region of the MHC; however, the 857T allele is not in linkagedisequilibrium with HLA alleles associated with ATL development.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 00:29:06