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

J Clin Oncol. 2004 Oct 1;22(19):3997-4001. doi: 10.1200/JCO.2004.10.059.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Receptors, Aryl Hydrocarbon / genetics*
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Sarcoma / therapy
  • Survival Rate

Substances

  • Receptors, Aryl Hydrocarbon