Genetic variants in apoptosis-related genes associated with colorectal hyperplasia

• Verfasst von: Gerola, Stefano [VerfasserIn]
• Verfasst von: Nittka, Stefanie [VerfasserIn]
• Verfasst von: Kähler, Georg [VerfasserIn]
• Verfasst von: Tao, Sha [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Binelli, Giorgio [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Brors, Benedikt [VerfasserIn]
• Verfasst von: Neumaier, Michael [VerfasserIn]
• Titel: Genetic variants in apoptosis-related genes associated with colorectal hyperplasia
• Verf.angabe: Stefano Gerola, Stefanie Nittka, Georg Kähler, Sha Tao, Hermann Brenner, Giorgio Binelli, Roland Eils, Benedikt Brors, and Michael Neumaier
• E-Jahr: 2014
• Jahr: 27 May 2014
• Umfang: 10 S.
• Fussnoten: Gesehen am 27.07.2020
• Titel Quelle: Enthalten in: Genes, chromosomes & cancer
• Ort Quelle: New York, NY : Wiley-Liss, 1989
• Jahr Quelle: 2014
• Band/Heft Quelle: 53(2014), 9, Seite 769-778
• ISSN Quelle: 1098-2264
• DOI: doi:10.1002/gcc.22185
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1725563053

Abstract

Deregulation of apoptosis is a frequent alteration in early benign lesions of the colon mucosa and is thought to be a major contributor to tumor progression and cancer. Single nucleotide polymorphisms (SNPs) within apoptosis-related genes could affect apoptotic responses and their identification might provide a basis to assess individual risk for development of early lesions. To investigate a possible association between genetic polymorphisms and the occurrence of hyperplastic polyps (HP), we developed a custom DNA chip assay for 1,536 SNPs in the coding and flanking regions of 826 genes with known functional roles in apoptosis or apoptosis-associated (e.g., stress-related) pathways. During a first round of screening, genotypes were determined for 272 endoscopy patients harboring hyperplastic colorectal polyps and for 512 sex and aged-matched controls. A set of 14 candidate SNPs associated with HP (P < 0.01) was then evaluated in an independent cohort of patients (n = 38) and controls (n = 38). Following meta-analysis of Stages I and II, a false discovery rate approach was applied. Among the 14 candidate SNPs, eight showed significant association (combined P < 0.01) with the occurrence of HP. The SNPs rs4709583 (PARK2) and rs10476823 (HDAC3) were analyzed for potential functional effects on RNA splicing and RNA half-life. Despite its location near a splice site, alternative splicing was not detected for rs4709583 (PARK3). By contrast, cDNA analysis revealed use of a cryptic polyadenylation signal in the 3′UTR of HDAC3 mRNA and a longer mRNA half-life in a cell line heterozygous for rs10476823. © 2014 Wiley Periodicals, Inc.