Exploratory analysis of Fas gene polymorphisms in pediatric osteosarcoma patients. Defective apoptosis signaling by the Fas pathway has carcinogenic implications. We analyzed 123 pediatric patients with osteosarcoma for Fas single nucleotide polymorphisms: 2 of the promoter region (-1377 G>A and -670 A>G) and 2 of the coding region (exon 3 18272 A>G and exon 7 22628 C>T). As a comparison group, we used 510 adults without a history of cancer. We found an increased risk of osteosarcoma associated with the heterozygous genotype Fas exon 3 AG (genotype frequency 19.5% in cases vs. 12.0% in controls, P=0.028; adjusted odds ratio=1.6, 95% confidence interval=0.9-2.7], and this association was more pronounced in non-Hispanic whites (20.6% in cases vs. 10.1% in controls, P=0.014; adjusted odds ratio=2.3, 95% confidence interval=1.2-4.6). Additionally, the frequency of the variant allele (exon 3 G) was significantly higher in cases than in controls for both the entire group and non-Hispanic whites (P=0.046 and P=0.030, respectively). We found no significant association between osteosarcoma risk and the other Fas polymorphisms. This study suggests an association between the Fas exon 3 A>G polymorphism and osteosarcoma risk; however, further study is needed with pediatric controls and a larger sample size.