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.

• Genetic polymorphism
• Colorectal neoplasia
• p53R2
• SSCP
• PCR-RFLP

• Adenoma/genetics
• Adult
• Aged
• Case-Control Studies
• Colorectal Neoplasms/genetics
• Female
• Gene Expression Regulation
• Genes, p53
• Genetic Variation
• Humans
• Male
• Middle Aged
• Ribonucleotide Reductases/genetics
• Tumor Suppressor Protein p53/metabolism

• R01 CA066539 NCI NIH HHS
• R03 CA092773 NCI NIH HHS

AIM: To investigate the pathogenic mechanism of colon cancer at the molecular level and to elucidate the relationship between intercellular adhesion molecule-1 (ICAM-1) and nm23H₁ genes and Chinese patients with colon cancer.

METHODS: DNA was extracted from paraffin-embedded materials. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze MSI and LOH. Expression of ICAM-1 was detected by Envision immuno-histochemistry. Experimental results were analyzed with Leica-Qwin computer imaging techniques and SPSS software of statistics.

RESULTS: ICAM-1 expression of lymphatic endothelium was negative in normal colon and positive in colon cancer respectively. The number of lymphatics positive for ICAM-1 was gradually increased with degree of cancer invasion (P < 0.01). In the group with metastasis of colon cancer, the number of lymphatics positive for ICAM-1 in lymph nodes was more than that in the group with no metastasis (P < 0.01). The frequency of MSI, LOH and nm23H₁ protein was 26.67%, 20.00% and 53.33% in colon cancer, respectively. In TNM staging, MSI (43.75%) and nm23H₁ protein (81.25%) in stages I + II were detected more easily than the corresponding indexes (MSI: 7.14%, P < 0.05 and nm23H₁: 21.43%, P < 0.01) in stages III + IV. By comparison, the frequency of LOH (35.71%) in stages III + IV was more than that of LOH (6.25%, P < 0.05) in stages I + II. LOH exhibited a rising trend along with the Duke’s staging. nm23H₁ protein in the group of tubular adenocarcinoma (60.00%) was higher expressed than that in the group of mucoid adenocarcinoma (20.00%) (P < 0.01), and exhibited a rising trend with the differentiation degrees of tubular adenocarcinoma. nm23H₁ protein in MSI positive group was higher expressed (75%) than that in MSI negative group (45.45%, P < 0.05).

CONCLUSION: The expression of ICAM-1 in lymphatic vessels is beneficial to the judgement of the invasion and metastasis ability of colon cancer and the anti-tumor immunity function, and shows an important clinical significance in predicting lymphatic metastasis of colon cancer. MSI and LOH may separately control the development of sporadic colon cancer with different pathways. LOH mostly arises in the late period of sporadic colon cancer and endows a high aggressive and poor prognostic phenotype. By compassion, MSI may be an early period molecule marker for sporadic colon cancer, enhanced expression of nm23H₁ protein can effectively inhibit colon cancer metastasis and improve prognosis of sporadic colon cancer patients.

• Adult
• Aged
• Biomarkers, Tumor/genetics
• China
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Female
• Humans
• Intercellular Adhesion Molecule-1/genetics
• Loss of Heterozygosity
• Lymphatic Metastasis
• Male
• Middle Aged
• NM23 Nucleoside Diphosphate Kinases
• Neoplasm Invasiveness
• Nucleoside-Diphosphate Kinase/genetics
• Polymerase Chain Reaction
• Polymorphism, Single-Stranded Conformational