hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type.
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.
Okasaka
Toshiki
T
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Matsuo
Keitaro
K
Suzuki
Takeshi
T
Ito
Hidemi
H
Hosono
Satoyo
S
Kawase
Takakazu
T
Watanabe
Miki
M
Yatabe
Yasushi
Y
Hida
Toyoaki
T
Mitsudomi
Tetsuya
T
Tanaka
Hideo
H
Yokoi
Kohei
K
Tajima
Kazuo
K
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003545:Cysteine / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012694:Serine / Q000235:genetics; D012907:Smoking
D012694:Serine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003545:Cysteine