Functional FEN1 genetic variants and haplotypes are associated with glioma risk
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LABORATORY INVESTIGATION
Functional FEN1 genetic variants and haplotypes are associated with glioma risk Yi-Dong Chen • Xiaojiao Zhang • Xiao-Guang Qiu Jinpeng Li • Qipeng Yuan • Tao Jiang • Ming Yang
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Received: 26 June 2012 / Accepted: 19 November 2012 / Published online: 27 November 2012 Ó Springer Science+Business Media New York 2012
Abstract As a tumor suppressor, FEN1 plays an essential role in keeping genomic instability and preventing tumorigenesis. There are two functional genetic variants (–69G[A and 4150G[T) in the FEN1 gene, which have been associated with DNA damage levels in coke-oven workers as well as risks of lung cancer, hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer in general populations. However, it is still unknown how these polymorphisms and their haplotypes are associated with glioma risk. Therefore, we investigated the role of these polymorphisms in glioma development using a case–control design in a Yi-Dong Chen and Xiaojiao Zhang contribute equally to this study.
Electronic supplementary material The online version of this article (doi:10.1007/s11060-012-1007-0) contains supplementary material, which is available to authorized users. Y.-D. Chen Department of Radiation Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China X. Zhang Q. Yuan M. Yang (&) College of Life Science and Technology, Beijing University of Chemical Technology, P. O. Box 53, Beijing 100029, China e-mail: [email protected] X.-G. Qiu Glioma Institute of Tiantan Hospital, Capital Medical University, Beijing, China J. Li Department of Intervention Surgery, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong, China T. Jiang (&) Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China e-mail: [email protected]
Chinese population. The impact of the haplotypes constructed by these two polymorphisms on glioma risk was also examined. It was observed that the FEN1–69GG or 4150GG genotype were significantly associated to increased glioma risk compared with the –69AA or 4150TT genotype [Odds ratios (OR) = 1.87, 95 % confidence interval (CI) = 1.232.85, P = 0.003; or OR = 1.87, 95 % CI = 1.23-2.84, P = 0.003). The associations were more pronounced among female subjects (For –69AG or GG genotype: OR = 2.35, 95 % CI = 1.22-4.52; for 4150TG or GG genotype: OR = 2.33, 95 % CI = 1.21-4.48) and patients with grade 1 or 2 disease (For –69AG or GG genotype: OR = 2.21, 95 % CI = 1.20-4.05; for 4150TG or GG genotype: OR = 2.45, 95 % CI = 1.31-4.58). Additionally, the G-69G4150 haplotype was also significantly associated with increased glioma risk compared with the A-69T4150 haplotype. Our results suggest that FEN1 polymorphisms and haplotypes are associated with glioma risk. Keywords FEN1 Polymorphism Haplotype Glioma Susceptibility
Introduction Flap endonuclease 1 (FEN1) is a multiple-function nuclease, involving DNA base-excision repair (BER) and DNA replication. On one hand, FEN1 could effic
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