Association of CYP1A1 gene variants rs4646903 (T>C) and rs1048943 (A>G) with cervical cancer in a North Indian population.

OBJECTIVE

To evaluate the association of CYP1A1 gene polymorphisms with cervical cancer susceptibility in general and in relation to tobacco smoking.

STUDY DESIGN

The study included 408 subjects from North India (208 controls and 200 cases). All subjects were genotyped for CYP1A1 m1 T>C (rs4646903) and m2 A>G (rs1048943) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by statistical analysis (SPSS, version 15.0; SHEsis online version).

RESULTS

In our population, individuals with TC and CC genotypes of CYP1A1 m1 polymorphism have significantly higher risk of cervical cancer (adjusted odds (OR) 2.76, P=0.001; 3.13, P=0.006 respectively). In the case of m2 polymorphism, individuals with AG and GG genotypes show increased risk of cervical cancer (OR 1.90, P=0.021; and 3.05, P=0.285 respectively). The 'C' allele of m1 and 'G' allele of m2 polymorphism were strongly associated with the disease (P<0.0001 and 0.008 respectively). Multiple combinations showed that women carrying the genotypes viz. TC/AA (+/-), TC/AG (+/+), CC/AG (-/+) and CC/AG (+/+) were at higher risk of developing cervical cancer. The relationship between CYP1A1 m1 and m2 genotypes and tobacco smoking showed an 8-11-fold higher risk of cervical cancer amongst active smokers and 3-4-fold in passive smokers as well. Linkage disequilibrium between m1 and m2 showed highly significant association in the case of TA* (P<0.0001) haplotype, while 'CG' appeared to be the risk haplotype (P=0.002).

CONCLUSION

Our results suggest that presence of the 'C' allele of m1 (T>C) and 'G' of m2 (A>G) may be the risk alleles for cervical cancer susceptibility. Moreover, CYP1A1 m1 and m2 polymorphisms show considerable association with tobacco smoking in our study population.