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


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.


CONCLUSIONS
Further study of the role of the AhR polymorphism is warranted.
Memorial Sloan-Kettering Cancer Center, New York, NY, USA. mberwick@salud.unm.edu
Marianne
M
Berwick
Giuseppe
G
Matullo
Yan Shuang
YS
Song
Simonetta
S
Guarrera
Gemma
G
Dominguez
Irene
I
Orlow
Mary
M
Walker
Paolo
P
Vineis
D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015996:Survival Rate
D018336:Receptors, Aryl Hydrocarbon