title: Clinical significance of a novel single nucleotide polymorphism in the 5' untranslated region of the Rabphillin-3A-Like gene in colorectal adenocarcinoma.
abstract: The recently identified human ortholog of the Rabphillin-3A-Like (RPH3AL) gene, located at the 17p13.3 locus, has been assessed for its mutational status and clinical significance in colorectal adenocarcinoma (CRC). Prospectively collected 95 frozen CRCs and their matching benign colonic epithelial tissues were evaluated for mutations and mRNA expression. Since, we observed a higher incidence of a single nucleotide polymorphism (SNP) at the -25 position in the 5'untranslated region (5'UTR-25) of RPH3AL, we performed the genotyping analysis of this SNP in a retrospective CRC cohort (n=134) to assess their clinical importance. Univariate and multivariate outcome analyses were performed. The cDNA analysis has detected point mutations in 6 CRCs, coding region SNPs in 14 CRCs, and non-coding region SNPs in 38 CRCs. Combined analyses of both cohorts has demonstrated that the incidence of SNP at 5'UTR-25 was 41% (95 of 229), and its A/A genotype (9%, 20 of 229) was observed exclusively in non-Hispanic Caucasians, and 19 of these cases were diagnosed with nodal metastasis. Patients who exhibited homozygous for A or C alleles had a significantly decreased levels of mRNA expression, increased risk of CRC recurrence and mortality. Therefore, these findings have significant clinical implications in assessing the aggressiveness of CRC.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-7331, USA.
authors.forename: Venkat R
authors.initials: VR
authors.lastname: Katkoori
authors.forename: Xu
authors.initials: X
authors.lastname: Jia
authors.forename: Chakrapani
authors.initials: C
authors.lastname: Chatla
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.forename: Selvarangan
authors.initials: S
authors.lastname: Ponnazhagan
authors.forename: Tom
authors.initials: T
authors.lastname: Callens
authors.forename: Ludwine
authors.initials: L
authors.lastname: Messiaen
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Upender
authors.initials: U
authors.lastname: Manne
mesh_terms: D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012189:Retrospective Studies; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C120704:RPH3AL protein, human; D020691:rab GTP-Binding Proteins