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Rare HRAS1 alleles are a risk factor for the development of brain tumors
Author(s) -
Vega Ana,
Sobrido María J.,
RuizPonte Clara,
Barros Francisco,
Carracedo Angel
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20011201)92:11<2920::aid-cncr10110>3.0.co;2-s
Subject(s) - allele , odds ratio , glioma , biology , locus (genetics) , pathology , genotype , minisatellite , medicine , genetics , microsatellite , gene
BACKGROUND The highly polymorphic HRAS1 minisatellite locus, located 1 kilobase downstream from the H‐ ras 1 gene, has been associated with increased susceptibility to a variety of cancers. Microsatellite instability (MI), another molecular abnormality observed in human neoplasms, most likely reflects an increased mutation rate and also is thought to underlie cancer predisposition. The purpose of this study was to investigate the association between rare HRAS1 alleles and brain tumors and to correlate the HRAS1 allelotype with MI and clinicopathologic features. METHODS Ninety‐four patients with primary brain tumors (52 gliomas, 32 meningiomas, and 10 schwannomas) and 109 healthy control individuals were studied. The size of HRAS1 alleles was determined by fluorescent detection in an automated DNA sequencer. The interspersion pattern was assessed by the minisatellite 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 (Fisher exact test; P = 0.0329). The presence of rare alleles was associated with an increased risk of brain tumors (odds ratio, 1.99; 95% confidence interval, 0.93–4.27). The overrepresentation 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 HRAS1 alleles and MI in their series. No significant difference in the distribution of these alleles was found when tumors were compared according to other clinicopathologic variables. CONCLUSIONS The presence of rare HRAS1 alleles is associated with an increased 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 suggests that these two genetic factors are not likely to be expression of the same underlying defect. Cancer 2001;92:2920–6. © 2001 American Cancer Society.