title: The significance of Exo1 K589E polymorphism on cancer susceptibility: evidence based on a meta-analysis.
abstract: The exonuclease1 (Exo1) gene is a key component of mismatch repair (MMR) by resecting the damaged strand, which is the only exonuclease involved in the human MMR system. The gene product is a member of the RAD2 nuclease family and functions in DNA replication, repair and recombination. However, whether Exo1 is required to activate MMR-dependent DNA damage response (DDR) remains unknown, the conclusions of the Exo1 polymorphisms on cancer susceptibility studies were not consistent. We carried out a meta-analysis of 7 case-control studies to clarify the association between the Exo1 K589E polymorphism and cancer risk. Overall,a significant association of the Exo1 K589E polymorphism with cancer risk in all genetic models (Lys vs Glu: OR = 1.51, 95%CI:1.39-1.99, P<0.01; Glu/Lys vs Glu/Glu: OR = 1.43, 95%CI:1.28-1.60, P<0.01; Lys/Lys vs Glu/Glu: OR = 2.45, 95%CI:1.90-3.17, P<0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR = 1.53, 95%CI:1.38-1.71, P<0.01; Glu/Glu vs Glu/Lys+Lys/Lys: OR =  2.27, 95%CI:1.79-2.89, P<0.01). In the stratified analysis by ethnicity, significantly increased risk was observed in Asian population (Lys vs Glu: OR = 1.53, 95%CI:1.39-1.69, P<0.01; Glu/Lys vs Glu/Glu: OR = 1.50, 95%CI:1.34-1.69, P<0.01; Lys/Lys vs Glu/Glu: OR = 2.48, 95%CI:1.84-3.34, P<0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR = 1.58, 95%CI:1.41-1.78, P<0.01; Glu/Glu vs Glu/Lys+Lys/Lys: OR = 2.18, 95%CI:1.62-2.93, P<0.01). Subgroup analysis based on smoking suggested Exo1 K589E polymorphism conferred significant risk among smokers (Lys/Lys+Glu/Lys vs Glu/Glu: OR = 2.16, 95%CI:1.77-2.63, P<0.01), but not in non-smokers (Lys/Lys+Glu/Lys vs Glu/Glu: OR = 0.89, 95%CI:0.64-1.24, P = 0.50). In conclusion, Exo1 K589E Lys allele may be used as a novel biomarker for cancer susceptibility, particularly in smokers.
authors.affiliation: Department of Hospital Infection Management, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou, Henan, China.
authors.forename: Fujiao
authors.initials: F
authors.lastname: Duan
authors.affiliation: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, Henan, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Dai
authors.affiliation: College of Professional Study, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Shuli
authors.initials: S
authors.lastname: Cui
authors.affiliation: Department of Hospital Infection Management, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou, Henan, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hospital Infection Management, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou, Henan, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
mesh_terms: D045643:DNA Repair Enzymes / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes