Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years

Skuladottir, Halla; Autrup, Herman; Autrup, Judith L.; Tjoenneland, Anne; Overvad, Kim; Ryberg, David; Haugen, Aage; Olsen, Jørgen H.

doi:10.1016/j.lungcan.2004.10.013

Cited by 38 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Twenty-one case-control studies examining the effect of NQO1 Pro187Ser polymorphisms on the risk of lung cancer were identified (16,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45); one study was only identified from citation (34), and one was an unpublished study (44). We excluded one study due to the lack of genotype information (37).…”

Section: Resultsmentioning

confidence: 99%

“…The genotype distributions in controls were in agreement with Hardy-Weinberg equilibrium for all studies. Subjects in the pooled study by Skuladottir et al (39), focusing on lung cancer risk for subjects under 60 years, seemed to overlap by about 100 cases and 100 controls with the subjects in Sorensen's study (40). Therefore, we only included subjects over 60 years from Sorensen's study in the overall metaanalysis to avoid double counting.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis

Chao

Zhang

Berthiller³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, their less toxic form. A sequence variant at position 609 (C ! T) in the NQO1 gene encodes an enzyme with reduced quinone reductase activity in vitro and thus was hypothesized to affect cancer susceptibility. We conducted meta-analyses focusing on three cancer sites (lung, bladder, and colorectum) to summarize the findings from the current literature and to explore sources of heterogeneity. Results: There is no clear association between the NQO1 Pro187Ser polymorphism and lung cancer risk in the three ethnic groups examined: odds ratio (OR White ) C/T + T/T versus C/C = 1.04 [95% confidence interval (95% CI), 0.96-1.13], OR Asian = 0.99 (95% CI, 0.72-1.34), and OR Blacks = 0.95 (95% CI, 0.66-1.36). However, a modestly increased risk was suggested for the variant homozygotes in whites (OR T/T versus C/C, 1.19; 95% CI, 0.94-1.50). Analysis excluding one outlier study suggested the variant allele may be associated with reduced lung cancer risk in Asians. Meta-analyses for bladder and colorectal cancer suggested a statistically significant association with the variant genotypes in whites. In stratified analyses, the NQO1 Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians. Conclusions: Results from our meta-analyses suggest that the variant NQO1 Pro187Ser genotype may affect individual susceptibility to lung, bladder, and colorectal cancer. Such effects of the NQO1 polymorphism seem to be modified by ethnicity and smoking status.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis

Chao

Zhang

Berthiller³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…Recent meta-analyses and pooled analyses indicate no effect of GSTM1 null genotype on lung cancer risk but do show combined effects of CYP1A1MspI and CYP1A1I462V polymorphisms with GSTM1 null in increasing lung cancer risk (20,21,27). Mixed results have been obtained in studies of GSTP1 polymorphisms and lung cancer (69)(70)(71)(72)(73)(74)(75)(76). Our data do not show consistent significant effects of GSTM1 null or GSTP1 polymorphisms on phenanthrene metabolism, but as discussed above, a significant increase in PheT/HOPhe ratios was observed in individuals with combined CYP1A1 I462V polymorphism and GSTM1 null genotype, consistent with theory and with previous studies.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Polymorphisms in Genes Involved in Polycyclic Aromatic Hydrocarbon Metabolism with Urinary Phenanthrene Metabolite Ratios in Smokers

Hecht

Carmella

Yoder

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The hypothesis that interindividual differences among smokers in the metabolism of polycyclic aromatic hydrocarbons (PAH) are related to lung cancer risk has been extensively investigated in the literature. These studies have compared lung cancer risk in groups of smokers with or without polymorphisms in genes involved in PAH metabolism. We believe that carcinogen metabolite phenotyping, involving the actual measurement of PAH metabolites, would be a better way to investigate differences in lung cancer risk. With this goal in mind, we have developed methods for quantifying phenanthrene metabolites in urine. Phenanthrene is the simplest PAH with a bay region, a feature closely associated with carcinogenicity. The urinary metabolite r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) is a measure of metabolic activation, whereas phenanthrols (HOPhe) are a measure of detoxification. In this study, we quantified urinary PheT/HOPhe ratios in 346 smokers who were also genotyped for 11 polymorphisms in genes involved in PAH metabolism: CYP1A1MspI, CYP1A1I462V, CYP1B1R48G, CYP1B1A119S, CYP1B1L432V, CYP1B1N453S, EPHX1Y113H, EPHX1H139R, GSTP1I105V, GSTP1A114V, and GSTM1 null. The geometric mean molar PheT/3-HOPhe ratio was 4.08 (95% confidence interval, 3.79-4.39). Ten percent of the smokers had PheT/3-HOPhe ratios of z9.90. We found a significant association between the presence of the CYP1A1I462V polymorphism and high PheT/3-HOPhe ratios (P = 0.02). This effect was particularly strong in females and in combination with the GSTM1 null polymorphism. In contrast, the CYP1B1R48G and CYP1B1A119S polymorphisms were associated with significantly lower PheT/3-HOPhe ratios, particularly in Blacks. There were no consistent significant effects of any of the other polymorphisms on PheT/3-HOPhe ratios. The highest 10% of PheT/3-HOPhe ratios could not be predicted by the presence of any of the 11 polymorphisms individually or by certain combinations. The effects of the CYP1A1I462 polymorphism observed here, particularly in combination with GSTM1 null, are quite consistent with reports in the literature. However, the results of this study indicate that genotyping is not an effective way to predict PAH metabolism at least as represented by PheT/HOPhe ratios.

show abstract

“…Previous studies 8,35,36,39,45 indicated an inverse association between MPO and lung cancer in men, whereas others did not confirm the result. 26,41,43,46 Although we did not observe statistically significant differences with gender, the protective effect of the A allele seemed to be more pronounced in males than in females, after adjustment for several confounding factors.…”

Section: Discussionmentioning

confidence: 81%

“…In vitro studies suggest that estrogens increase the MPO A allele promoter activity by several fold; females carrying at least one MPO A allele have been reported as having significantly higher levels of DNA adducts than those carrying the MPO G/G genotype. 48 Another published finding is that the MPO G-463A polymorphism may be more protective toward lung cancer in younger individuals, 8,35,36,39,45 although other studies did not confirm this observation 26,40,43,46 or reported the opposite. 38,44 MPO activity has been reported to be lower in women with the -463GA genotype who are aged less than 45 years than in those aged more than 55 years with the same genotype.…”

Section: Discussionmentioning

confidence: 98%

Myeloperoxidase G-463A polymorphism and lung cancer: A HuGE Genetic Susceptibility to Environmental Carcinogens pooled analysis

Taioli

Benhamou

Bouchardy³

et al. 2007

Genetics in Medicine

View full text Add to dashboard Cite

Myeloperoxidase is a phase I metabolic enzyme that converts the metabolites of benzo [a]pyrene from tobacco smoke into highly reactive epoxides. A polymorphism in the promoter region of myeloperoxidase (463G¡A) has been found to be inversely associated with lung cancer; differences in the association with age and gender have been suggested. We conducted a pooled analysis of individual data from 10 studies (3688 cases and 3874 controls) from the Genetic Susceptibility to Environmental Carcinogens database. The odds ratio for lung cancer

show abstract

Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years

Cited by 38 publications

References 53 publications

NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis

NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and the Risk of Lung, Bladder, and Colorectal Cancers: a Meta-analysis

Comparison of Polymorphisms in Genes Involved in Polycyclic Aromatic Hydrocarbon Metabolism with Urinary Phenanthrene Metabolite Ratios in Smokers

Myeloperoxidase G-463A polymorphism and lung cancer: A HuGE Genetic Susceptibility to Environmental Carcinogens pooled analysis

Contact Info

Product

Resources

About