title: Possible association between genetic variants in the H2AFX promoter region and risk of adult glioma in a Chinese Han population.
abstract: H2AFX, a histone H2A gene family member X, is a key component in the detection of and response to DNA double-strand breaks (DSBs) caused by ionizing radiation (IR), a known risk factor for glioma. Thus, genetic variants in the H2AFX promoter region that may result in abnormal protein expression could confer susceptibility to glioma. In this case-control study, we genotyped three common single-nucleotide polymorphisms (SNPs) (rs643788, rs8551, and rs2509851) in the H2AFX promoter region in 669 adult glioma patients and 638 cancer-free controls. The associations between each SNP or haplotype and glioma risk were estimated by calculating odds ratios (ORs) and the corresponding 95% confidence interval (CI) using unconditional logistic regression models, with adjustment for age and sex. The H2AFX rs643788 A variant genotypes were significantly associated with reduced risk of glioma (GA versus GG: adjusted OR = 0.72, 95% CI = 0.56-0.94; GA/AA versus GG: adjusted OR = 0.75, 95% CI = 0.59-0.94), compared with the common GG genotype. Furthermore, this decreased risk was more evident among those aged ≥ 45 years (adjusted OR = 0.64, 95% CI = 0.45-0.90), male subjects (adjusted OR = 0.70, 95% CI = 0.50-0.96), and patients with glioblastoma (adjusted OR = 0.66, 95% CI = 0.46-0.94). These results suggest that a common variant in the H2AFX promoter region may modulate risk of glioma, particularly for adult glioma. However, our findings need to be replicated in other independent populations.
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes for Biomedical Sciences, Fudan University, 220 Handan Rd, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Keke
authors.initials: K
authors.lastname: Zhou
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Tianbao
authors.initials: T
authors.lastname: Zhang
authors.forename: Guhong
authors.initials: G
authors.lastname: Du
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006657:Histones / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: C468783:H2AX protein, human; D006657:Histones