title: Genetic variation on 9p22 is associated with abnormal ovarian ultrasound results in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
abstract: BACKGROUND
  A recent ovarian cancer genome-wide association study (GWAS) identified a locus on 9p22 associated with reduced ovarian cancer risk. The single nucleotide polymorphism (SNP) markers localize to the BNC2 gene, which has been associated with ovarian development.
  
  
  METHODS
  We analyzed the association of 9p22 SNPs with transvaginal ultrasound (TVU) screening results and CA-125 blood levels from participants without ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO); 1,106 women with adequate ultrasound screening results and available genotyping information were included in the study.
  
  
  RESULTS
  We observed a significantly increased risk of abnormal suspicious TVU results for seven SNPs on 9p22, with odds ratios between 1.68 (95% CI: 1.04-2.72) for rs4961501 and 2.10 (95% CI: 1.31-3.38) for rs12379183. Associations were restricted to abnormal suspicious findings at the first TVU screen. We did not observe an association between 9p22 SNPs and CA-125 levels.
  
  
  CONCLUSIONS
  Our findings suggest that 9p22 SNPs, which were found to be associated with decreased risk of ovarian cancer in a recent GWAS, are associated with sonographically detectable ovarian abnormalities. Our results corroborate the relevance of the 9p22 locus for ovarian biology. Further studies are required to understand the complex relationship between screening abnormalities and ovarian carcinogenesis and to evaluate whether this locus can influence the risk stratification of ovarian cancer screening.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America. wentzenn@mail.nih.gov
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.forename: Kevin
authors.initials: K
authors.lastname: Jacobs
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Neil
authors.initials: N
authors.lastname: Caporaso
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.forename: Lawrence
authors.initials: L
authors.lastname: Ragard
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Buys
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
mesh_terms: D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods* / Q000706:statistics & numerical data; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: C484527:BNC2 protein, human; D018394:CA-125 Antigen; D004268:DNA-Binding Proteins