Melin, Beatrice2; Dahlin, Anna M2; Andersson, Ulrika2; Wang, Zhaoming2; Henriksson, Roger2; Hallmans, Göran2; Bondy, Melissa L2; Johansen, Christoffer4; Feychting, Maria2; Ahlbom, Anders2; Kitahara, Cari M2; Wang, Sophia S2; Ruder, Avima M2; Carreón, Tania2; Butler, Mary Ann2; Inskip, Peter D2; Purdue, Mark2; Hsing, Ann W2; Mechanic, Leah2; Gillanders, Elizabeth2; Yeager, Meredith2; Linet, Martha2; Chanock, Stephen J2; Hartge, Patricia2; Rajaraman, Preetha2
1 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
a case-control gene association study
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.
International Journal of Cancer. Journal International Du Cancer, 2013, Vol 132, Issue 10, p. 2464-2468
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Case-Control Studies; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; DNA Helicases; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Glioblastoma; Glioma; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Sweden; Telomerase; United States