title: Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase Risk of Uterine Cervical Cancer.
abstract: OBJECTIVE
  Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer.
  
  
  METHODS
  Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed.
  
  
  RESULTS
  The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type.
  
  
  CONCLUSIONS
  The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.
authors.affiliation: Biometric Research Branch, National Cancer Center, Goyang, Korea.
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.affiliation: Lung Cancer Branch, National Cancer Center, Goyang, Korea.
authors.forename: Kyong-Ah
authors.initials: KA
authors.lastname: Yoon
authors.affiliation: Department of Radiobiology and Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Translational Epidemiology Research Branch and Department of Laboratory Medicine, National Cancer Center, Goyang, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.affiliation: Radiation Medicine Branch, National Cancer Center, Goyang, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Biometric Research Branch, National Cancer Center, Goyang, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Park
authors.affiliation: Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Hematologic Malignancy Branch and Department of Laboratory Medicine, National Cancer Center, Goyang, Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea.
authors.forename: Jeongseon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, Korea.|Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.affiliation: Radiation Medicine Branch, National Cancer Center, Goyang, Korea.|Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C497292:ERCC2 protein, human
keywords: ERCC; Single nucleotide polymorphism; Uterine cervical neoplasms