title: Tumor and reproductive traits are linked by RNA metabolism genes in the mouse ovary: a transcriptome-phenotype association analysis.
abstract: BACKGROUND
  The link between reproductive life history and incidence of ovarian tumors is well known. Periods of reduced ovulations may confer protection against ovarian cancer. Using phenotypic data available for mouse, a possible association between the ovarian transcriptome, reproductive records and spontaneous ovarian tumor rates was investigated in four mouse inbred strains. NIA15k-DNA microarrays were employed to obtain expression profiles of BalbC, C57BL6, FVB and SWR adult ovaries.
  
  
  RESULTS
  Linear regression analysis with multiple-test control (adjusted p ≤ 0.05) resulted in ovarian tumor frequency (OTF) and number of litters (NL) as the top-correlated among five tested phenotypes. Moreover, nearly one-hundred genes were coincident between these two traits and were decomposed in 76 OTF(-) NL(+) and 20 OTF(+) NL(-) genes, where the plus/minus signs indicate the direction of correlation. Enriched functional categories were RNA-binding/mRNA-processing and protein folding in the OTF(-) NL(+) and the OTF(+) NL(-) subsets, respectively. In contrast, no associations were detected between OTF and litter size (LS), the latter a measure of ovulation events in a single estrous cycle.
  
  
  CONCLUSIONS
  Literature text-mining pointed to post-transcriptional control of ovarian processes including oocyte maturation, folliculogenesis and angiogenesis as possible causal relationships of observed tumor and reproductive phenotypes. We speculate that repetitive cycling instead of repetitive ovulations represent the actual link between ovarian tumorigenesis and reproductive records.
authors.affiliation: Laboratorio de Genómica Aplicada, ICBM, Universidad de Chile, Independencia 1027, Santiago, Chile. uurzua@med.uchile.cl
authors.forename: Ulises
authors.initials: U
authors.lastname: Urzúa
authors.forename: Garrison A
authors.initials: GA
authors.lastname: Owens
authors.forename: Gen-Mu
authors.initials: GM
authors.lastname: Zhang
authors.forename: James M
authors.initials: JM
authors.lastname: Cherry
authors.forename: John J
authors.initials: JJ
authors.lastname: Sharp
authors.forename: David J
authors.initials: DJ
authors.lastname: Munroe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D016014:Linear Models; D051379:Mice; D008815:Mice, Inbred Strains; D046228:Microarray Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D012098:Reproduction / Q000502:physiology*; D013045:Species Specificity
chemical_list: D012313:RNA