Urzúa et al. BMC Genomics 2010, 11(Suppl 5):S1 http://www.biomedcentral.com/1471-2164/11/S5/S1 P R O C E E D I N G S Open Access Tumor and reproductive traits are linked by RNA metabolism genes in the mouse ovary: a transcriptome-phenotype association analysis Ulises Urzúa1*, Garrison A Owens2, Gen-Mu Zhang3, James M Cherry2, John J Sharp4, David J Munroe2 From 5th International Conference of the Brazilian Association for Bioinformatics and Computational Biology (X-meeting 2009) Angra Dos Reis, RJ, Brazil. 18-22 October 2009 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. Conclusion: 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. Background Epidemiological evidence indicates that multiparity and breastfeeding as well as endocrine disrupting agents - used in oral contraception, hormone replacement ther- apy and infertility treatment- modulate the risk of ovar- ian cancer [1]. Repetitive lifetime ovulations would induce a persistent wound repair process of the ovarian surface epithelium cells leading to pre-neoplastic altera- tions [2]. In addition, oral contraceptives and pregnancy reduce levels of circulating gonadotropins whereas * Correspondence: uurzua@med.uchile.cl 1Laboratorio de Genómica Aplicada, ICBM, Universidad de Chile, Independencia 1027, Santiago, Chile Full list of author information is available at the end of the article fertility drugs induce follicle-stimulating hormone (FSH) production. Gonadotropins also increase with reproduc- tive ageing, and have been implicated in ovarian cancer etiology since this malignancy predominantly occurs in menopausal women [3]. The laboratory mouse has been increasingly used to model several aspects of ovarian cancer [4]. Indeed, reproductive biology of mouse resembles human repro- duction in many aspects. Analogous to menstrual cycles in women, female mice undergo estrous cycles that last 4-5 days and consist of four successive phases. Proestrus and estrous phases together constitute the follicular phase while metestrus and diestrus phases together represent the luteal phase [5]. Similar to humans, the © 2010 Urzúa et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.