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The impact of genetic polymorphisms in  CYP1A1  on susceptibility to lung cancer has received particular interest in recent years since this enzyme plays a central role in activation of major classes of tobacco carcinogens. Several polymorphisms in the  CYP1A1  locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. We have assessed the role of  CYP1A1  genotype in lung cancer risk in the Chinese population via a case–control study. Three polymorphisms,  m1  ( Msp I),  m2  (exon 7 Ile→Val) and  m4  (exon 7 Thr→Asn), were determined by PCR–RFLP in 404 controls and 217 lung cancer cases. While no polymorphic alleles were detectable in the m4 site among our study subjects, the allele frequencies for  CYP1A1 m1  and  CYP1A1 m2  were found to be 35.6 and 25.6% among controls, compared with 42.6 and 34.2% among cases. Multivariate analysis showed an elevated risk for lung cancer in subjects having at least one  m1  allele [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.4–2.8] or having at least one  m2  allele (OR = 1.9, 95% CI = 1.3–2.7). However, this increased risk was limited to squamous cell carcinoma (SCC), but not adenocarcinoma or other histological types of lung cancer. Stratified analysis indicated a multiplicative interaction between tobacco smoking and variant  CYP1A1 m1  genotypes on the risk of SCC. The ORs of SCC for the variant  CYP1A1 m1  genotype, tobacco smoking and both factors combined were 2.8, 9.1 and 29.9, respectively. When the data was stratified by the pack-year values, this joint effect was consistent and stronger among the heaviest smokers. The interaction between tobacco smoking and the variant  CYP1A1 m2  genotypes followed the same pattern. Our findings support the conclusion that  CYP1A1 m1  and  CYP1A1 m2  polymorphisms are associated with smoking-related lung cancer risk in Chinese.

CYP 1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case–control study in China