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Association Between Aryl Hydrocarbon Receptor Genotype and Survival in Soft Tissue Sarcoma

From the Memorial Sloan-Kettering Cancer Center; Cornell University Medical School, New York, NY; Institute for Scientific Interchange; University of Turin, Turin, Italy; University of New Mexico, Albuquerque, NM; and Imperial College, London, United Kingdom

Address reprint requests to Marianne Berwick, PhD, MPH, 1 University of New Mexico, MSC08 4630, CRF 103A, Albuquerque, NM 87131; e-mail: mberwick{at}salud.unm.edu

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.

Supported by an institutional grant to M.B. from Memorial Sloan-Kettering Cancer Center and by the Kristin Ann Carr Fund for Sarcoma Research.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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