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Prospective study of urinary excretion of 7‐methylguanine and the risk of lung cancer: Effect modification by mu class glutathione‐ S ‐transferases
Author(s) -
Loft Steffen,
Svoboda Peter,
Kasai Hiroshi,
Tjønneland Anne,
Møller Peter,
Sørensen Mette,
Overvad Kim,
Autrup Herman,
RaaschouNielsen Ole
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22863
Subject(s) - lung cancer , excretion , medicine , confounding , gstp1 , urine , cancer , population , prospective cohort study , gastroenterology , oncology , genotype , physiology , biology , genetics , environmental health , gene
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 GSTM 1 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 GSTM 1 null genotype supports causality in this respect. © 2007 Wiley‐Liss, Inc.