Rare HRAS1 alleles are a risk factor for the development of brain tumors

Background. The highly polymorphic HRAS1 minisatellite locus, located I kil obase downstream from the H-ras1 gene, has been associated with increased s usceptibility to a variety of cancers. Microsatellite instability (MI), ano ther molecular abnormality observed in human neoplasms, most likely reflect s an increased mutation rate and also is thought to underlie cancer predisp osition. The purpose of this study was to investigate the association betwe en rare HRAS1 alleles and brain tumors and to correlate the HRAS1 allelotyp e with MI and clinicopathologic features. Methods. Ninety-four patients with primary brain tumors (52 gliomas, 32 men ingiomas, and 10 schwannomas) and 109 healthy control individuals were stud ied. The size of HRAS1 alleles was determined by fluorescent detection in a n automated DNA sequencer. The interspersion pattern was assessed by the mi nisatellite variant repeat-polymerase chain reaction technique. Results. Twenty of 94 (21.28%) patients with brain tumors had at least one rare allele, compared with 13 of 109 (11.92%) in the control population (Fi sher exact test, P=0.0329). The presence of rare alleles was associated wit h an increased risk of brain tumors (odds ratio, 1.99; 95% confidence inter val, 0.93-4.27). The over representation of rare alleles in tumor patients mainly reflects the higher frequency observed in the glioma group (P=0.0086 ). The authors did not detect association between the presence of rare HRAS 1 alleles and MI in their series. No significant difference in the distribu tion of these alleles was found when tumors were compared according to othe r clinicopathologic variables. Conclusions. The presence of rare HRAS1 alleles is associated with an in cr eased risk for the development of glial neoplasms (OR=2.72; 95% CI, 1.17-6. 32). The lack of association between rare HRAS1 polymorphisms and MI sugges ts that these two genetic factors are not likely to be expression of the sa me underlying defect. Cancer 2001;92:2920-6. (C) 2001 American Cancer Socie ty.