title: MicroRNA processing and binding site polymorphisms are not replicated in the Ovarian Cancer Association Consortium.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies.
  
  
  METHODS
  We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset.
  
  
  RESULTS
  After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk.
  
  
  CONCLUSIONS
  Common variants in these evaluated genes do not seem to be strongly associated with EOC risk.
  
  
  CONCLUSIONS
  This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered.
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Permuth-Wey
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Tsai
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Y Ann
authors.initials: YA
authors.lastname: Chen
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: David
authors.initials: D
authors.lastname: Fenstermacher
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Jesus
authors.initials: J
authors.lastname: Gonzalez-Bosquet
authors.forename: Edwin
authors.initials: E
authors.lastname: Iversen
authors.forename: Heather
authors.initials: H
authors.lastname: Jim
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phelan
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sutphen
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tyrer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Johnathan M
authors.initials: JM
authors.lastname: Lancaster
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
mesh_terms: D001665:Binding Sites; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D035683:MicroRNAs