Abstract

<div>Abstract<p>MicroRNAs (miRNA) play important roles in tumorigenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the regulatory effect of miRNAs to their target genes, hence promoting tumorigenesis. This study analyzed 226 single nucleotide polymorphisms (SNP) in miRNA processing genes and miRNA binding sites in 339 ovarian cancer cases and 349 healthy controls to assess association with cancer risk, overall survival, and treatment response. Thirteen polymorphisms were found to have significant association with risk. The most significant were 2 linked SNPs (r<sup>2</sup> = 0.99), rs2740351 and rs7813 in <i>GEMIN4</i> [odds ratio (OR) = 0.71; 95% confidence interval (CI), 0.57–0.87 and OR = 0.71; 95% CI, 0.57–0.88, respectively]. Unfavorable genotype analysis showed the cumulative effect of these 13 SNPs on risk (<i>P</i> for trend < 0.0001). Potential higher order gene–gene interactions were identified, which categorized patients into different risk groups according to their genotypic signatures. In the clinical outcome study, 24 SNPs exhibited significant association with overall survival and 17 SNPs with treatment response. Notably, patients carrying a rare homozygous genotype of rs1425486 in <i>PDGFC</i> had poorer overall survival [hazard ratio (HR) = 2.69; 95% CI, 1.67–4.33] and worse treatment response (OR = 3.38; 95% CI, 1.39–8.19), compared to carriers of common homozygous and heterozygous genotypes. Unfavorable genotype analyses also showed a strong gene-dosage effect with decreased survival and increased risk of treatment nonresponse in patients with greater number of unfavorable genotypes (<i>P</i> for trend < 0.0001). Taken together, miRNA-related genetic polymorphisms may impact ovarian cancer predisposition and clinical outcome both individually and jointly. <i>Cancer Res; 70(23); 9765–76. ©2010 AACR</i>.</p></div>

Full Text

Published Version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.