Runt-related transcription factor 3: single nucleotide polymorphism rs760805, gene expression, and methylation status in Helicobacter pylori -infected patients for determination of gastric cancer risk.

Abstract

PURPOSE:

Repression of Runt-related transcription factor 3 (Runx3) gene, a tumor suppressor, has been known to be involved in Helicobacter pylori (H. pylori)-associated gastric carcinogenesis and cancer development. The present study was undertaken to study the Runx3 intronic T/A polymorphism (rs760805) in H. pylori-infected patients and uninfected controls of Tamil Nadu region, South India. Also, Runx3 gene expression, HK alpha (H,K-ATPase) gene expression and the methylation status of the Runx3 CpG island was determined.

METHODS:

In a prospective study, tissue biopsies were collected from 40 H. pylori-infected patients and 40 infection negative controls. Single nucleotide polymorphism analysis was carried out by polymerase chain reaction (PCR)-single-strand conformational polymorphism, and DNA sequencing. Gene expression analysis of Runx3 and HK alpha was carried out using semiquantitative reverse transcriptase-PCR. Methylation analysis of Runx3 CpG island was undertaken using methylationspecific restriction digestion-PCR.

RESULTS:

The homozygous TT genotype was found to be the predominant genotype in positive samples and negative controls. No significant variation in gene expression was observed in positive samples and controls with respect to Runx3 and Hk alpha genes. Methylation analysis suggested that there was a lack of methylation except in a few subjects studied.

CONCLUSION:

The present study, first from this region, could neither detect significant repression of the Runx3 and HK alpha genes nor methylation in positive patients studied suggesting a lack of involvement of this tumor suppressor as a risk factor in the H. pylori-associated gastric carcinogenesis in the South Indian population studied.

• Authors: Nithya Nadarajan, Lakshman Kumar Balasubramanian, Suresh Kuppannan, Chandirasekar Ramachandran, Venkatakrishnan Leelakrishnan
• Journal: Journal of gastrointestinal cancer (J Gastrointest Cancer) Vol. 44 Issue 4 Pg. 444-9 (Dec 2013) ISSN: 1941-6636 [Electronic] United States
• PMID: 23959374 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Core Binding Factor Alpha 3 Subunit
• RNA, Messenger
• Runx3 protein, human

Topics

• Case-Control Studies
• Core Binding Factor Alpha 3 Subunit (genetics, metabolism)
• DNA Methylation
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic (physiology)
• Helicobacter Infections (genetics, microbiology, pathology)
• Helicobacter pylori (pathogenicity)
• Humans
• Neoplasm Staging
• Polymorphism, Single Nucleotide (genetics)
• Polymorphism, Single-Stranded Conformational
• Prognosis
• Promoter Regions, Genetic (genetics)
• Prospective Studies
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Stomach Neoplasms (genetics, microbiology, pathology)