title: The Association of Flap Endonuclease 1 Genotypes with the Risk of Childhood Leukemia.
abstract: OBJECTIVE
  Flap endonuclease 1 (FEN1) is one of the most important proteins in maintaining genome stability and preventing carcinogenesis. In recent years, the contribution of two variants of FEN1, rs174538 and rs4246215, regarding cancer risk have been investigated in lung, breast, liver, esophageal, gastric, colorectal cancer and glioma. However, it has not been revealed whether rs174538 and rs4246215 are associated with leukemia. Therefore, in the present study we aimed to evaluate the contribution of these genotypic polymorphisms in FEN1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan.
  
  
  METHODS
  In total, 266 patients with childhood ALL and an equal number of recruited non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
  
  
  RESULTS
  The FEN1 rs174538 genotype, but not rs4246215, was differently distributed between childhood ALL and control groups. The AG and AA of FEN1 rs174538 genotypes were significantly less frequently found in childhood ALL patients than in controls (odds ratio [OR]=0.68 and 0.48, 95%confidence intervals [CI]=0.47-0.98 and 0.24-0.82, respectively). As for gender, boys carrying the FEN1 rs174538 AG or AA genotype conferred lower ORs of 0.55 and 0.36 (95%CI=0.33-0.91 and 0.18-0.73, p=0.0053) for childhood ALL. Regarding age, those equal to or greater than 3.5 years of age at onset carrying the FEN1 rs174538 AG or AA genotype were of lower risk (ORs=0.53 and 0.32, 95%CI=0.31-0.90 and 0.15-0.70, p=0.0042).
  
  
  CONCLUSIONS
  The FEN1 rs174538 A allele is a protective biomarker for childhood ALL and this association is more significant in males and in patients at onset age of 3.5 years or older.
authors.affiliation: Departments of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors.forename: Jen-Sheng
authors.initials: JS
authors.lastname: Pei
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Departments of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Hsu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chin-Mu
authors.initials: CM
authors.lastname: Hsu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Hong-Xue
authors.initials: HX
authors.lastname: Ji
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Chieh-Lun
authors.initials: CL
authors.lastname: Hsiao
authors.affiliation: Family Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors.forename: Yuan-Nian
authors.initials: YN
authors.lastname: Hsu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C. datian@mail.cmuh.org.tw artbau2@gmail.com.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
mesh_terms: D016022:Case-Control Studies; D002648:Child; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D045585:Flap Endonucleases; C468317:FEN1 protein, human
keywords: Childhood leukemia; FEN1; Taiwan; genotype; polymorphism