PURPOSE: Accumulating evidence shows that germline polymorphisms may affect survival in cancer. The purpose of this study was to investigate the association between polymorphisms in a group of candidate genes and survival with soft tissue sarcoma. PATIENTS AND METHODS: We measured single nucleotide polymorphisms in the metabolizing, detoxifying, and DNA repair pathways in 120 newly diagnosed patients with soft tissue sarcoma. We assessed polymorphisms in the aryl hydrocarbon receptor (AhR-Arg554Lys), null variants of the glutathione S-transferase superfamily (GSTM1 and GSTT1), x-ray repair cross-complementing 1 and 3, and Xeroderma pigmentosum, group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln). We followed the patients for survival for a median of 7.6 years. RESULTS: Cox proportional hazards models demonstrated that a polymorphism at codon 554 in exon 10 of the AhR was significantly and adversely associated with survival (hazard ratio, 2.2; 95% CI, 1.3 to 3.9; P <.01), even while accounting for major clinical characteristics such as tumor grade, tumor size, anatomic site, and patient age. CONCLUSION: Further study of the role of the AhR polymorphism is warranted.
Titolo: | Association between aryl hydrocarbon receptor genotype and survival in soft tissue sarcoma | |
Autori Riconosciuti: | ||
Autori: | BERWICK M; MATULLO G; SONG YS; GUARRERA S; DOMINGUEZ G; ORLOW I; WALKER M; VINEIS P | |
Data di pubblicazione: | 2004 | |
Abstract: | PURPOSE: Accumulating evidence shows that germline polymorphisms may affect survival in cancer. The purpose of this study was to investigate the association between polymorphisms in a group of candidate genes and survival with soft tissue sarcoma. PATIENTS AND METHODS: We measured single nucleotide polymorphisms in the metabolizing, detoxifying, and DNA repair pathways in 120 newly diagnosed patients with soft tissue sarcoma. We assessed polymorphisms in the aryl hydrocarbon receptor (AhR-Arg554Lys), null variants of the glutathione S-transferase superfamily (GSTM1 and GSTT1), x-ray repair cross-complementing 1 and 3, and Xeroderma pigmentosum, group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln). We followed the patients for survival for a median of 7.6 years. RESULTS: Cox proportional hazards models demonstrated that a polymorphism at codon 554 in exon 10 of the AhR was significantly and adversely associated with survival (hazard ratio, 2.2; 95% CI, 1.3 to 3.9; P <.01), even while accounting for major clinical characteristics such as tumor grade, tumor size, anatomic site, and patient age. CONCLUSION: Further study of the role of the AhR polymorphism is warranted. | |
Volume: | 22(19) | |
Pagina iniziale: | 3997 | |
Pagina finale: | 4001 | |
Digital Object Identifier (DOI): | 10.1200/JCO.2004.10.059 | |
URL: | http://jco.ascopubs.org/cgi/reprint/22/19/3997 | |
Parole Chiave: | aryl hydrocarbon receptor; DNA repair polymorphisms; survival; soft tissue sarcoma | |
Rivista: | JOURNAL OF CLINICAL ONCOLOGY | |
Appare nelle tipologie: | 03A-Articolo su Rivista |