title: Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.
abstract: Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. beatrice.melin@onkologi.umu.se
authors.forename: Beatrice
authors.initials: B
authors.lastname: Melin
authors.forename: Anna M
authors.initials: AM
authors.lastname: Dahlin
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.forename: Maria
authors.initials: M
authors.lastname: Feychting
authors.forename: Anders
authors.initials: A
authors.lastname: Ahlbom
authors.forename: Cari M
authors.initials: CM
authors.lastname: Kitahara
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Avima M
authors.initials: AM
authors.lastname: Ruder
authors.forename: Tania
authors.initials: T
authors.lastname: Carreón
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Butler
authors.forename: Peter D
authors.initials: PD
authors.lastname: Inskip
authors.forename: Mark
authors.initials: M
authors.lastname: Purdue
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Leah
authors.initials: L
authors.lastname: Mechanic
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gillanders
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Martha
authors.initials: M
authors.lastname: Linet
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Preetha
authors.initials: P
authors.lastname: Rajaraman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D019098:Telomerase / Q000235:genetics; D014481:United States
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; C509186:TERT protein, human; D019098:Telomerase; C532890:RTEL1 protein, human; D004265:DNA Helicases