Journal of neuro-oncology · 2006
Genetic variation in p53 and ATM haplotypes and risk of glioma and meningioma.
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Malmer Beatrice Susanne, Feychting Maria, Lönn Stefan, Lindström Sara, Grönberg Henrik, Ahlbom Anders, Schwartzbaum Judy, Auvinen Anssi, Collatz-Christensen Helle, Johansen Christoffer, Kiuru Anne, Mudie Nadejda, Salminen Tiina, Schoemaker Minouk J, Swerdlow Anthony J, Henriksson Roger
Аннотация
BACKGROUND: P53 and ATM are central checkpoint genes involved in the repair of DNA damage after ionising irradiation, which has been associated with risk of brain tumours. Therefore, we tested the hypothesis that polymorphisms and haplotypes in p53 and ATM could be associated with glioma and meningioma risk.
MATERIAL AND METHODS: Six hundred and eighty glioma cases (298 glioblastoma (GBM)), 503 meningioma cases, and 1555 controls recruited in the Nordic-UK Interphone study, were analysed in association with three polymorphisms in p53 (rs2287499, rs1042533, rs1625895) and five polymorphisms in ATM ( rs228599, rs3092992, rs664143, rs170548, rs3092993). Haplotypes were constructed using the HAPLOSTAT program.
RESULTS: The global statistical test of glioblastoma and p53 haplotypes was p = 0.02. The haplotype analysis on glioblastoma revealed the 1-2-2 haplotype (promotor-codon72-intron 6) had a frequency of 6.1% in cases compared with 9.8% in controls (p = 0.003). The 1-2-1 haplotype was significantly more frequent in GBM cases, 10.2%, than in controls, 7.3% (p = 0.02). The haplotype analysis in ATM revealed an increased frequency of the 1-1-1-2-1 haplotype in meningioma cases (33.8%) compared with controls (30.3%) (p = 0.03). The 2-1-2-1-1 haplotype had a lower frequency in meningioma cases (36.1%) than controls (40.7%) (p = 0.009).
CONCLUSIONS: This study found both positive and negative associations of haplotypes in p53 for glioblastoma and ATM for meningioma. This study provides new data that could add to our understanding of brain tumour susceptibility.
MATERIAL AND METHODS: Six hundred and eighty glioma cases (298 glioblastoma (GBM)), 503 meningioma cases, and 1555 controls recruited in the Nordic-UK Interphone study, were analysed in association with three polymorphisms in p53 (rs2287499, rs1042533, rs1625895) and five polymorphisms in ATM ( rs228599, rs3092992, rs664143, rs170548, rs3092993). Haplotypes were constructed using the HAPLOSTAT program.
RESULTS: The global statistical test of glioblastoma and p53 haplotypes was p = 0.02. The haplotype analysis on glioblastoma revealed the 1-2-2 haplotype (promotor-codon72-intron 6) had a frequency of 6.1% in cases compared with 9.8% in controls (p = 0.003). The 1-2-1 haplotype was significantly more frequent in GBM cases, 10.2%, than in controls, 7.3% (p = 0.02). The haplotype analysis in ATM revealed an increased frequency of the 1-1-1-2-1 haplotype in meningioma cases (33.8%) compared with controls (30.3%) (p = 0.03). The 2-1-2-1-1 haplotype had a lower frequency in meningioma cases (36.1%) than controls (40.7%) (p = 0.009).
CONCLUSIONS: This study found both positive and negative associations of haplotypes in p53 for glioblastoma and ATM for meningioma. This study provides new data that could add to our understanding of brain tumour susceptibility.
Предметные рубрики MeSH
AdultAgedAtaxia Telangiectasia Mutated ProteinsBrain NeoplasmsCase-Control StudiesCell Cycle ProteinsDNA-Binding ProteinsFemaleGenetic Predisposition to DiseaseGliomaHaplotypesHumansMaleMeningeal NeoplasmsMeningiomaMiddle AgedPolymorphism, Single NucleotideProtein Serine-Threonine KinasesRisk FactorsTumor Suppressor Protein p53Tumor Suppressor Proteins