hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type.

Abstract

Human 8-oxoguanine DNA glycosylase 1 (hOGG1) has a major role in the repair of 8-hydroxyguanine, a major promutagenic DNA lesion. The genetic polymorphism rs1052133, which leads to substitution of the amino acid at codon 326 from Ser to Cys, shows functional differences, namely a decrease in enzyme activity in hOGG1-Cys326. Although several studies have investigated the association between rs1052133 and lung cancer susceptibility, the effect of this locus on lung cancer according to histology remains unclear. We therefore conducted a case-control study with 515 incident lung cancer cases and 1030 age- and sex-matched controls without cancer, and further conducted a meta-analysis. In overall analysis, the homozygous Cys/Cys genotype showed a significant association with lung cancer compared to Ser allele carrier status (odds ratio (OR)=1.31, 95% confidence interval (CI)=1.02-1.69). By histology-based analysis, the Cys/Cys genotype showed a significantly positive association with small-cell carcinoma (OR=2.40, 95% CI=1.32-4.49) and marginally significant association with adenocarcinoma (OR=1.32, 95% CI=0.98-1.77). A meta-analysis of previous and our present study revealed that this polymorphism is positively associated with adenocarcinoma, although suggestive associations were also found for squamous- and small-cell lung cancers. These results indicate that rs1052133 contributes to the risk of adenocarcinoma of lung.

• Authors: Toshiki Okasaka, Keitaro Matsuo, Takeshi Suzuki, Hidemi Ito, Satoyo Hosono, Takakazu Kawase, Miki Watanabe, Yasushi Yatabe, Toyoaki Hida, Tetsuya Mitsudomi, Hideo Tanaka, Kohei Yokoi, Kazuo Tajima
• Journal: Journal of human genetics (J Hum Genet) Vol. 54 Issue 12 Pg. 739-45 (Dec 2009) ISSN: 1435-232X [Electronic] England
• PMID: 19881468 (Publication Type: Journal Article)

Chemical References

• Serine
• DNA Glycosylases
• oxoguanine glycosylase 1, human
• Cysteine

Topics

• Adenocarcinoma (genetics, pathology)
• Adult
• Aged
• Carcinoma, Small Cell (genetics, pathology)
• Carcinoma, Squamous Cell (genetics, pathology)
• Case-Control Studies
• Cysteine (genetics)
• DNA Glycosylases (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Humans
• Lung Neoplasms (genetics, pathology)
• Male
• Meta-Analysis as Topic
• Middle Aged
• Multivariate Analysis
• Mutation, Missense
• Odds Ratio
• Polymorphism, Single Nucleotide
• Risk Factors
• Serine (genetics)
• Smoking