Colorectal Cancer
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2005; 11(33): 5169-5173
Published online Sep 7, 2005. doi: 10.3748/wjg.v11.i33.5169
Novel genetic variations of the p53R2 gene in patients with colorectal adenoma and controls
Zong-Lin Deng, Da-Wen Xie, Roberd M Bostick, Xi-Jiang Miao, You-Ling Gong, Jin-Hui Zhang, Michael J Wargovich
Zong-Lin Deng, Da-Wen Xie, You-Ling Gong, Jin-Hui Zhang, Department of Epidemiology and Biostatistics, University of South Carolina School of Public Health and South Carolina Cancer Center, Columbia SC 29203, United States
Roberd M Bostick, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, United States
Xi-Jiang Miao, Department of Computer Science and Engineering, University of South Carolina, Columbia SC 29201, United States
You-Ling Gong, Tumor Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Michael J Wargovich, Department of Pathology, University of South Carolina School of Medicine and South Carolina Cancer Center, Columbia SC 29203, United States
Author contributions: All authors contributed equally to the work.
Supported by the No. R03 CA92773-01A1 Grant to DX and No.R01 CA66539 Grant to RMB from the National Cancer Institute from National Institutes of Health, Department of Health and Human Services
Correspondence to: Dr. Da-Wen Xie, University of South Carolina, 14 Richland Medical Park, Suite 500, Columbia, SC 29203, United States. dawen.xie@palmettohealth.org
Telephone: +1-803-434-3707 Fax: +1-803-434-3795
Received: January 12, 2005
Revised: February 15, 2005
Accepted: February 18, 2005
Published online: September 7, 2005
Abstract

AIM: p53-Inducible ribonucleotide reductase small subunit 2 (p53R2) encodes a 351-amino-acid peptide, which catalyzes conversion of ribonucleoside diphosphates to the corresponding deoxyribonucleotides required for DNA replication and repair. A recent study reported that a point mutation (G/T) in the p53 binding sequence in a colon cancer cell line completely impaired p53R2 protein activity.

METHODS: We screened the p53R2 gene coding regions and a regulatory region which contains a p53 binding sequence in 100 patients with colorectal adenoma and 100 control subjects using PCR, cold SSCP, and direct DNA sequencing.

RESULTS: Although we did not identify genetic variation in all nine exons, four regulatory-region variants were found, of which three were single nucleotide polymorphisms (SNPs) (nt 1 789 C/G, nt 1 928 A/G, 1 933 T/C), and one was 20 bp insertion which replaced a ATTTT between nt 1 831 and 1 835. Additionally, we determined the frequency of these p53R2 variants in a recently concluded case-control study of incident sporadic colorectal adenomas (163 cases and 210 controls).

CONCLUSION: Although more detailed functional characterizations of these polymorphisms remain to be undertaken, these polymorphic sites may be useful for identifying alleles associated with mis-splicing, additional transcript factors and, more generally, in cancer-susceptibility association studies.

Keywords: Genetic polymorphism; Colorectal neoplasia; p53R2; SSCP; PCR-RFLP