Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: A case-control study in Japanese nonsmoking women

Chikako Kiyohara, Kenji Wakai, Haruo Mikami, Koichi Sido, Masahiko Ando, Yoshiyuki Ohno

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60 Citations (Scopus)

Abstract

Genetic backgrounds may modify the association of environmental tobacco smoke (ETS) with lung cancer risk. Polymorphisms of both the activating and detoxifying enzymes, cytochrome P4S01A1 (CYP1A1) and glutathione-S-transferase MI (GSTM1), may be important as genetic factors. We conducted a multicenter case-control study in Japanese nonsmoking women. Cases were women aged 30-89 years and newly diagnosed as having lung cancer from November 1997 to March 2001 in 4 study areas. We also recruited age-matched (5-year strata) and hospital-matched nonsmoking controls. A total of 158 cases and 259 hospital controls supplied blood for genotyping. Detailed information on ETS exposure from husbands and that in other situations and on potential confounders was collected by interview. Odds ratios (ORs) were estimated by using conditional logistic models. We found no increase in the risk of lung cancer for CYP1A1 Msp I genotypes. For the GSTM1 null genotype vs. nonnull genotype, the OR was 1.37 [95% confidence interval (CI) 0.90-2.09], which indicated a somewhat increased risk for the GSTM1 null genotype. A gene-environment interaction was suggested, with combined GSTM1 null genotype and high-dose ETS exposure (≥40 pack-years by husbands) conferring significantly higher risk (OR = 2.27, 95% CI 1.13-4.57) compared to the GSTM1 null genotype and low-dose ETS exposure (<40 pack-years). Our results do not support a major role of Msp I polymorphism of the CYP1A1 gene as a risk factor for lung cancer among nonsmoking women. In contrast, the GSTM1 null genotype posed an increased, although not significant, risk among them. Additional studies are warranted to confirm the ETS-GSTM1 polymorphism interaction suggested in our present study.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalInternational Journal of Cancer
Volume107
Issue number1
DOIs
Publication statusPublished - Oct 20 2003

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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