Prospective study of urinary excretion of 7-methylguanine and the risk of lung cancer: Effect modification by mu class glutathione-S-transferases.

2.50
Hdl Handle:
http://hdl.handle.net/10146/36754
Title:
Prospective study of urinary excretion of 7-methylguanine and the risk of lung cancer: Effect modification by mu class glutathione-S-transferases.
Authors:
Loft, Steffen; Svoboda, Peter; Kasai, Hiroshi; Tjonneland, Anne; Moller, Peter; Sorensen, Mette; Overvad, Kim; Autrup, Herman; Raaschou-Nielsen, Ole
Abstract:
Nitrosamines are mainly mutagenic through methylation of DNA. 7-Methylguanine (m(7)Gua) is a product of base excision repair and spontaneous depurination of such lesions in DNA and a metabolite from RNA. Associations between urinary excretion of m(7)Gua and risk of lung cancer were examined in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years. During 3-7 years follow-up 260 cases with lung cancer were identified and a subcohort of 263 individuals matched on sex, age and smoking duration was selected for comparison. Urine collected at entry was analyzed for m(7)Gua by HPLC. Effect modification by glutathione-S-transferases GSTM1, GSTM3, GSTT1 and GSTP1 was investigated. We found higher excretion of m(7)Gua among current smokers than among former smokers. The IRR (incidence rate ratio) of lung cancer was 1.20 (95% CI: 1.00-1.43) per doubling of m(7)Gua excretion in unadjusted analysis and 1.12 (95% CI: 0.93-1.35) after adjustment for smoking status, intensity and duration at entry. This association was mainly present among current smokers. Comparing the highest with the lowest tertile of m(7)Gua excretion the IRR of lung cancer was 1.75 (95% CI: 1.04-2.95) irrespective of genotype and 2.75 (95% CI: 1.33-5.81) in subjects with GSTM1 null genotype. If not caused by residual confounding by smoking a possible association between m(7)Gua excretion and lung cancer supports the importance of methylation of guanine. The finding of an association between m(7)Gua excretion and lung cancer risk mainly among current smokers and subjects with GSTM1 null genotype supports causality in this respect.
Citation:
Int. J. Cancer 2007, 121 (7):1579-1584
Journal:
International Journal of Cancer. Journal international du cancer
Issue Date:
1-Oct-2007
URI:
http://hdl.handle.net/10146/36754
DOI:
10.1002/ijc.22863
PubMed ID:
17565746
Additional Links:
http://www3.interscience.wiley.com/journal/114278532/abstract
Type:
Article
Language:
en
ISSN:
0020-7136
Sponsors:
Funded by: Danish Research Councils, Danish Cancer Society, Japan Society for the Promotion of Science and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence under the European Union 6th Framework Program Priority 5: Food Quality and Safety; Grant Number: 513943
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorLoft, Steffen-
dc.contributor.authorSvoboda, Peter-
dc.contributor.authorKasai, Hiroshi-
dc.contributor.authorTjonneland, Anne-
dc.contributor.authorMoller, Peter-
dc.contributor.authorSorensen, Mette-
dc.contributor.authorOvervad, Kim-
dc.contributor.authorAutrup, Herman-
dc.contributor.authorRaaschou-Nielsen, Ole-
dc.date.accessioned2008-08-28T11:43:16Z-
dc.date.available2008-08-28T11:43:16Z-
dc.date.issued2007-10-01-
dc.identifier.citationInt. J. Cancer 2007, 121 (7):1579-1584en
dc.identifier.issn0020-7136-
dc.identifier.pmid17565746-
dc.identifier.doi10.1002/ijc.22863-
dc.identifier.urihttp://hdl.handle.net/10146/36754-
dc.description.abstractNitrosamines are mainly mutagenic through methylation of DNA. 7-Methylguanine (m(7)Gua) is a product of base excision repair and spontaneous depurination of such lesions in DNA and a metabolite from RNA. Associations between urinary excretion of m(7)Gua and risk of lung cancer were examined in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years. During 3-7 years follow-up 260 cases with lung cancer were identified and a subcohort of 263 individuals matched on sex, age and smoking duration was selected for comparison. Urine collected at entry was analyzed for m(7)Gua by HPLC. Effect modification by glutathione-S-transferases GSTM1, GSTM3, GSTT1 and GSTP1 was investigated. We found higher excretion of m(7)Gua among current smokers than among former smokers. The IRR (incidence rate ratio) of lung cancer was 1.20 (95% CI: 1.00-1.43) per doubling of m(7)Gua excretion in unadjusted analysis and 1.12 (95% CI: 0.93-1.35) after adjustment for smoking status, intensity and duration at entry. This association was mainly present among current smokers. Comparing the highest with the lowest tertile of m(7)Gua excretion the IRR of lung cancer was 1.75 (95% CI: 1.04-2.95) irrespective of genotype and 2.75 (95% CI: 1.33-5.81) in subjects with GSTM1 null genotype. If not caused by residual confounding by smoking a possible association between m(7)Gua excretion and lung cancer supports the importance of methylation of guanine. The finding of an association between m(7)Gua excretion and lung cancer risk mainly among current smokers and subjects with GSTM1 null genotype supports causality in this respect.en
dc.description.sponsorshipFunded by: Danish Research Councils, Danish Cancer Society, Japan Society for the Promotion of Science and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence under the European Union 6th Framework Program Priority 5: Food Quality and Safety; Grant Number: 513943en
dc.language.isoenen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/114278532/abstracten
dc.subjectlung canceren
dc.subjectsmokingen
dc.subjectcohort studyen
dc.subjectbiomarkersen
dc.subject7-methylguanineen
dc.subjectglutathione-S-transferasesen
dc.subject.meshFemale-
dc.subject.meshGene Frequency-
dc.subject.meshGenotype-
dc.subject.meshGlutathione S-Transferase pi-
dc.subject.meshGlutathione Transferase-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshLinear Models-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMultivariate Analysis-
dc.subject.meshProspective Studies-
dc.subject.meshRegistries-
dc.subject.meshRisk Factors-
dc.subject.meshSmoking-
dc.titleProspective study of urinary excretion of 7-methylguanine and the risk of lung cancer: Effect modification by mu class glutathione-S-transferases.en
dc.typeArticleen
dc.identifier.journalInternational Journal of Cancer. Journal international du canceren

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