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Functional FEN1 genetic variants and haplotypes are associated with glioma risk

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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 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) = 1.23−2.85, 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.

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Acknowledgments

This work was supported by Beijing City Talent Training Project (no. 2012D009016000002 to M. Yang), Beijing Nova Program (no. 2010B013 to M. Yang), Beijing Natural Science Foundation (no. 5122020 to M. Yang); the Fundamental Research Funds for the Central Universities (no. ZZ1234 to M. Yang); National Natural Science Foundation of China (no. 31271382 & no. 81201586 to M. Yang) and National High-Tech Research and Development Program of China (2012AA02A508).

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The authors declare no competing financial interests.

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Correspondence to Tao Jiang or Ming Yang.

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Yi-Dong Chen and Xiaojiao Zhang contribute equally to this study.

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Chen, YD., Zhang, X., Qiu, XG. et al. Functional FEN1 genetic variants and haplotypes are associated with glioma risk. J Neurooncol 111, 145–151 (2013). https://doi.org/10.1007/s11060-012-1007-0

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