This study reports a C→A transversion at position 4887 in exon 7 of cytochrome P4501A1 (CYP1A1), resulting in a threonine→asparagine exchange in codon 461. The polymorphism is located directly beside the known codon 462-Ile/Val mutation (m2) near the heme binding region. The C4887A mutation leads to the loss of a BsaI cleavage site, which allows analysis. No linkage of this mutation, termed m4, with other mutations such as m1 (MspI polymorphism in the 3′-flanking region) or m2 was observed on the same DNA strand. Systematic molecular genetic analyses of mutation linkages revealed that mutation m2 is in strict linkage disequilibrium with m1. To distinguish the different CYP1A1 alleles and genotypes, mutation linkages were considered.

Frequency of the m4-containing allele, termed CYP1A1*4, among 880 unrelated Caucasian individuals was 2.95% (95% confidence limits, 2.21%, 3.86%). m1 was found in 7.73%, and m2 in 2.67% of alleles. No case of African black-specific mutation m3 was detected. The allele frequency of CYP1A1*4 among 157 lung cancer patients was 2.87% (95% confidence limits, 1.32%, 5.37%); it was 2.87% (95% confidence limits, 1.71%, 4.49%) in 314 controls matched by age and sex. Thus, the novel m4-mutation may not represent a susceptibility factor for lung cancer.

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This work was supported in part by Grant 01 EC 9408/0 from the German Federal Ministry of Education, Science, Research, and Technology.

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