Cancer · 2005
Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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Yang Ping, Kollmeyer Thomas M, Buckner Kristin, Bamlet William, Ballman Karla V, Jenkins Robert B
Аннотация
BACKGROUND: Deletions of 19q have been associated with gliomas, especially oligodendrogliomas. In addition, cases with oligodendrogliomas with the 19q deletion have been observed to have a better survival compared with cases without the 19q deletion. The authors have previously described a 150-kilobase minimal deletion region in gliomas that maps to 19q13.33 and contains 3 novel candidate genes (GLTSCR1, EHD2, and GLTSCR2).
METHODS: The authors performed an association study using 141 cases with gliomas (61 cases with astrocytomas, 40 cases with oligodendrogliomas, 40 cases with mixed oligoastrocytomas) and 108 general controls. They evaluated 7 single nucleotide polymorphisms (SNPs) in 6 genes within and nearby the minimal 19q deletion region (ERCC2, RAI, ASE-1, ERCC1, GLTSCR1, and LIG1).
RESULTS: The prevalence of a germline GLTSCR1-exon-1 T allele (SNP rs1035938) was 40% in cases with oligodendrogliomas compared with 27% in controls (P = 0.029), and the prevalence of an ERCC2-exon-22 T allele (SNP rs1052555) was 35% in cases with oligodendrogliomas compared with 18% in controls (P = 0.043). One high-risk and 1 low-risk haplotype were associated with oligodendroglioma development (P = 0.003 and 0.026, respectively). Cases with oligodendrogliomas with the 19q deletion had a significantly higher frequency of the GLTSCR1-exon-1 T allele compared with cases without the 19q deletion (P = 0.01). It was noteworthy that cases with gliomas who were homozygous for the GLTSCR1-exon-1 T allele had a significantly better survival: 77% and 68% survival at 2 and 5 years compared with 56% and 34% for other genotypes (P = 0.02, log-rank test). Multivariable analysis identified grade, age, and the GLTSCR1-exon-1 and ERCC2-exon-22 genotypes as independent predictors for survival.
CONCLUSIONS: These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of oligodendroglioma.
METHODS: The authors performed an association study using 141 cases with gliomas (61 cases with astrocytomas, 40 cases with oligodendrogliomas, 40 cases with mixed oligoastrocytomas) and 108 general controls. They evaluated 7 single nucleotide polymorphisms (SNPs) in 6 genes within and nearby the minimal 19q deletion region (ERCC2, RAI, ASE-1, ERCC1, GLTSCR1, and LIG1).
RESULTS: The prevalence of a germline GLTSCR1-exon-1 T allele (SNP rs1035938) was 40% in cases with oligodendrogliomas compared with 27% in controls (P = 0.029), and the prevalence of an ERCC2-exon-22 T allele (SNP rs1052555) was 35% in cases with oligodendrogliomas compared with 18% in controls (P = 0.043). One high-risk and 1 low-risk haplotype were associated with oligodendroglioma development (P = 0.003 and 0.026, respectively). Cases with oligodendrogliomas with the 19q deletion had a significantly higher frequency of the GLTSCR1-exon-1 T allele compared with cases without the 19q deletion (P = 0.01). It was noteworthy that cases with gliomas who were homozygous for the GLTSCR1-exon-1 T allele had a significantly better survival: 77% and 68% survival at 2 and 5 years compared with 56% and 34% for other genotypes (P = 0.02, log-rank test). Multivariable analysis identified grade, age, and the GLTSCR1-exon-1 and ERCC2-exon-22 genotypes as independent predictors for survival.
CONCLUSIONS: These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of oligodendroglioma.
Предметные рубрики MeSH
AstrocytomaBrain NeoplasmsCase-Control StudiesChromosome DeletionChromosomes, Human, Pair 19DNA HelicasesDNA RepairDNA-Binding ProteinsFemaleGenotypeHumansMaleMiddle AgedOligodendrogliomaPolymerase Chain ReactionPolymorphism, Single NucleotideSurvival RateTranscription FactorsTumor Suppressor ProteinsXeroderma Pigmentosum Group D Protein