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.