Novel genetic variations of the p53R2 gene in patients with colorectal adenoma and controls.
OBJECTIVE
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 1831 and 1835. 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).


CONCLUSIONS
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.
Deng
Zong-Lin
ZL
Department of Epidemiology and Biostatistics, University of South Carolina School of Public Health, 14 Richland Medical Park, Suite 500, Columbia, SC 29203, United States.
Xie
Da-Wen
DW
Bostick
Roberd M
RM
Miao
Xi-Jiang
XJ
Gong
You-Ling
YL
Zhang
Jin-Hui
JH
Wargovich
Michael J
MJ
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D016158:Genes, p53; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012264:Ribonucleotide Reductases / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit