The hOGG1 gene 5'-UTR variant c.-53G>C contributes to the risk of gastric cancer but not colorectal cancer in the Chinese population: the functional variation of hOGG1 for gastric cancer risk.

Abstract

PURPOSE:

The incidence and mortality of gastric and colorectal cancers are among the highest malignant tumors in China. The aim of this study is to investigate whether variations of the human oxoguanine glycosylase 1 (hOGG1) gene are related to the risk of gastric and colorectal cancers in the Chinese population.

METHODS:

There were 622 gastric cancer patients, 383 colorectal cancer patients, and 932 healthy controls recruited to screen for variations in the 5'untranslated region (UTR) and to screen for the missense mutation (p.Ser326Cys) in exon7 of the hOGG1 gene using high-resolution melting curve analysis (HRM) and subsequent sequencing. The promoter luciferase activity assay was applied to assess the potential influence of the detected variants on gene function.

RESULTS:

Four variations, c.-53G>C, c.-45G>A, c.-23A>G, and c.-18G>T, were detected in the 5'-UTR of the hOGG1 gene. The case-control study indicated that the c.-53G/C heterozygous genotype was markedly associated with gastric cancer (P = 0.008, OR = 2.304, 95% CI, 1.258-4.221), but not with colorectal cancer. The clinicopathological association analysis showed that the variant of c.-53G>C in the hOGG1 gene was prevalent in low-differentiation patients (P = 0.012, OR = 3.174, 95% CI: 1.352-7.448). This variant decreased the gene promoter activity by approximately 17.8% (P = 0.041) and exhibited a synergistic effect with the missense mutation p.Ser326Cys of hOGG1 by enhancing susceptibility to gastric cancers.

CONCLUSIONS:

The variant c.-53G>C in the 5'-UTR of the hOGG1 gene is a risk factor for gastric cancer and is potentially associated with low-differentiation degree, but not with colorectal cancer, in the Chinese population.

• Authors: Xiufang Liu, Nong Xiao, Wenwen Guo, Yijia Wu, Zhenming Cai, Qiong He, Lin Zhang, Xiaoxiang Chen, Caixia Sun, Jingmei Wang, Changdong Zhu, Heiying Jin, Yaping Wang
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 137 Issue 10 Pg. 1477-85 (Oct 2011) ISSN: 1432-1335 [Electronic] Germany
• PMID: 21822670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5' Untranslated Regions
• DNA Glycosylases
• oxoguanine glycosylase 1, human

Topics

• 5' Untranslated Regions (genetics)
• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms (etiology, genetics)
• DNA Glycosylases (genetics, physiology)
• Female
• Genotype
• HeLa Cells
• Humans
• Male
• Middle Aged
• Promoter Regions, Genetic
• Risk Factors
• Stomach Neoplasms (etiology, genetics)