title: Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer.
abstract: BACKGROUND
  Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer.
  
  
  RESULTS
  We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P(trend)<0.0001), and RPS19 rs2305809 (P(trend)=0.0007), respectively. Both SNPs were also associated with progression.
  
  
  CONCLUSIONS
  These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. safaeianm@mail.nih.gov
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Safaeian
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Carolina
authors.initials: C
authors.lastname: Porras
authors.forename: Qizhai
authors.initials: Q
authors.lastname: Li
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodriguez
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Robert
authors.initials: R
authors.lastname: Burk
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdette
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D003364:Costa Rica / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D061105:Peroxiredoxin III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011230:Precancerous Conditions / Q000453:epidemiology / Q000209:etiology*; D012269:Ribosomal Proteins / Q000235:genetics*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000209:etiology*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000209:etiology*
chemical_list: D012269:Ribosomal Proteins; C040343:ribosomal protein S19; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III