title: Functional FEN1 genetic variants and haplotypes are associated with glioma risk.
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(-69)G(4150) haplotype was also significantly associated with increased glioma risk compared with the A(-69)T(4150) haplotype. Our results suggest that FEN1 polymorphisms and haplotypes are associated with glioma risk.
authors.affiliation: Department of Radiation Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Chen
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Qiu
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Li
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics*; D056726:Genetic Association Studies; D005910:Glioma / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D045585:Flap Endonucleases; C468317:FEN1 protein, human