TY - JOUR
T1 - Possible association between genetic variants in the H2AFX promoter region and risk of adult glioma in a Chinese Han population
AU - Fan, Weiwei
AU - Zhou, Keke
AU - Zhao, Yingjie
AU - Wu, Wenting
AU - Chen, Hongyan
AU - Jin, Li
AU - Chen, Gong
AU - Shi, Jinlong
AU - Wei, Qingyi
AU - Zhang, Tianbao
AU - Du, Guhong
AU - Mao, Ying
AU - Lu, Daru
AU - Zhou, Liangfu
N1 - Funding Information:
Acknowledgments The authors would like to thank Xilan Mei, Jian Yu, and Mei Chong for subject enrollment, Yin Wang and Wenting Wu for laboratory assistance, and Dr. Melissa Bondy for providing the M.D. Anderson brain tumor questionnaire. We also thank all participants of the Department of Neurosurgery of Huashan Hospital for their cooperation during data collection. This work was supported by Shanghai Science and Technology Research Program 09JC1402200, Shanghai Leading Scientist for Public Health 08GWD07, and Shanghai Key Subject Project for Public Health 08GWZX0301.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Association study
KW - DNA repair
KW - Glioma
KW - H2AFX
KW - Tagging SNP
UR - http://www.scopus.com/inward/record.url?scp=82955198393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82955198393&partnerID=8YFLogxK
U2 - 10.1007/s11060-011-0586-5
DO - 10.1007/s11060-011-0586-5
M3 - Article
C2 - 21512825
AN - SCOPUS:82955198393
SN - 0167-594X
VL - 105
SP - 211
EP - 218
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -