Synergistic association of CYP1A1 polymorphisms with increased susceptibility to squamous cell lung cancer in north Indian smokers.

OBJECTIVES: Studies in different populations have shown that polymorphisms within the CYP1A1 gene play an important role in determining individual susceptibility to lung cancer. However, the data obtained so far have been contradictory within the same or different populations. Few studies have focused on the synergistic effect of CYP1A1 polymorphisms on the susceptibility to lung cancer overall and to different histological subtypes along with the impact of smoking.

METHODS: A total of 704 individuals (353 lung cancer patients and 351 controls) were evaluated for CYP1A1 polymorphisms. CYP1A1 genotyping was done by means of PCR-RFLP.

RESULTS: A CYP1A1 mutant genotype was found to be significantly associated with lung cancer (OR = 3.15; 95% CI = 1.75-5.71; p = 0.0001) and this risk was 4-fold higher in case of squamous cell carcinoma (SCC). The CYP1A1 m2 allelic variant was found to be strongly associated with the risk of SCC and adenocarcinoma. The combined "at risk" genotypes of the CYP1A1 m1 and m2 allelic variants were associated with lung cancer risk and this risk was higher in case of SCC (OR = 2.0; 95% CI = 1.97-3.81; p = 0.028). Furthermore, the lung cancer risk was associated with smoking, especially in heavy smokers carrying CYP1A1 variant genotypes. We also observed that heavy smokers with the mutant m1 genotype were at increased risk of SCC (OR = 5.4; 95% CI = 2.4-11.9; p<0.0001). Furthermore, when stratified for smoking dose and histology, the effect was compounded in heavy smokers and SCC (OR = 7.5; 95% CI = 1.8-30.9; p = 0.004).

CONCLUSIONS: Polymorphism in the CYP1A1 gene is an important risk modifier for lung cancer.