TY - JOUR
T1 - Reduced expression levels of nucleotide excision repair genes in lung cancer
T2 - A case-control analysis
AU - Cheng, Lie
AU - Spitz, Margaret R.
AU - Hong, Waun K.
AU - Wei, Qingyi
PY - 2000
Y1 - 2000
N2 - Epidemiological studies have indicated that reduced DNA repair capacity and increased DNA adduct levels are associated with increased risk of lung cancer. Nucleotide excision repair (NER) is the major pathway in humans for repairing DNA adducts induced by smoking-related carcinogens, such as benzo[a]pyrene diol epoxide. We hypothesized that genetically determined baseline expression level of genes involved in NER is associated with risk of lung cancer. In a pilot case-control study, we measured the relative expression levels of five NER genes [ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6 and XPC (ERCC, excision repair cross-complementing; CSB, Cockayne's syndrome complementary group B)] in phytohemagglutininstimulated peripheral lymphocytes obtained from 75 lung cancer patients and 95 controls using a newly developed multiplex RT-PCR assay. Cases and controls were matched on age, sex, ethnicity and tobacco use. The expression level of the β-actin gene was used as an internal control for the relative quantitation. We observed a 12.2 and 12.5% decrease in the baseline expression levels of XPG/ERCC5 and CSB/ERCC6, respectively, in cases compared with controls. These differences were statistically significant (P < 0.01) when the median expression level in the controls was used as the cut-off point, the lung cancer patients were significantly more likely than the controls to have reduced expression levels of XPG/ERCC5 [odds ratio (OR), 2.32; 95% confidence interval (CI), 1.22-4.43] and CSB/ERCC6 (OR, 2.49; 95% CI, 1.28-4.84). There was also a dose- response relationship between reduced expression levels and increased lung cancer risk (trend test: P < 0.01). Our results suggest that individuals whose expression levels of XPG/ERCC5 and CSB/ERCC6 are reduced may be at higher risk of lung cancer.
AB - Epidemiological studies have indicated that reduced DNA repair capacity and increased DNA adduct levels are associated with increased risk of lung cancer. Nucleotide excision repair (NER) is the major pathway in humans for repairing DNA adducts induced by smoking-related carcinogens, such as benzo[a]pyrene diol epoxide. We hypothesized that genetically determined baseline expression level of genes involved in NER is associated with risk of lung cancer. In a pilot case-control study, we measured the relative expression levels of five NER genes [ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6 and XPC (ERCC, excision repair cross-complementing; CSB, Cockayne's syndrome complementary group B)] in phytohemagglutininstimulated peripheral lymphocytes obtained from 75 lung cancer patients and 95 controls using a newly developed multiplex RT-PCR assay. Cases and controls were matched on age, sex, ethnicity and tobacco use. The expression level of the β-actin gene was used as an internal control for the relative quantitation. We observed a 12.2 and 12.5% decrease in the baseline expression levels of XPG/ERCC5 and CSB/ERCC6, respectively, in cases compared with controls. These differences were statistically significant (P < 0.01) when the median expression level in the controls was used as the cut-off point, the lung cancer patients were significantly more likely than the controls to have reduced expression levels of XPG/ERCC5 [odds ratio (OR), 2.32; 95% confidence interval (CI), 1.22-4.43] and CSB/ERCC6 (OR, 2.49; 95% CI, 1.28-4.84). There was also a dose- response relationship between reduced expression levels and increased lung cancer risk (trend test: P < 0.01). Our results suggest that individuals whose expression levels of XPG/ERCC5 and CSB/ERCC6 are reduced may be at higher risk of lung cancer.
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U2 - 10.1093/carcin/21.5.527
DO - 10.1093/carcin/21.5.527
M3 - Article
C2 - 10910954
AN - SCOPUS:0033854786
SN - 0143-3334
VL - 21
SP - 1527
EP - 1530
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -