Association between aryl hydrocarbon receptor genotype and survival in soft tissue sarcoma

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-Thr241 Met, XPD-Lys751 Gln). 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% Cl, 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. (C) 2004 by American Society of Clinical Oncology.