Genetic Polymorphisms of the Human Cytochrome P450 1A1 (CYP1A1) and Cervical Cancer Susceptibility among Northeast Thai Women

Abstract

Background: CYP1A1 is an enzyme in phase I of the cytochrome P450 (CYP) superfamily, and plays a key role in detoxification of carcinogens. Host genetic predisposition in the CYP1A1 may be associated with an increased susceptibility to cervical cancer.The study aimed to evaluate four common polymorphisms of the CYP1A1 and cervical cancer susceptibility among Northeast Thai women.

Methods: A case-control study was conducted involving 204 patients with squamous cell cervical cancer (SCCA) and 204 age-matched healthy controls. DNA was extracted from peripheral blood leucocytes. CYP1A1 m1, m3, and m4 genotypes were detected using PCR-RFLP, whereas the CYP1A1 m2 genotype was investigated using real-time PCR. Haplotype analysis was performed using PHASE algorithm version 2.1.1.

Results: CYP1A1 m3 was monomorphic. Association between the common CYP1A1 polymorphisms, m1 and m2, and cervical cancer risk was not observed (p>0.05), nor was any association found between the m1-m2-m4 haplotype and cervical cancer risk (p>0.05). Interestingly, the CA genotype of CYP1A1 m4 was observed in 30.88% of the cervical cancer patients but was absent in healthy controls.

Conclusion: Our results demonstrated a possible involvement of the CYP1A1 m4 polymorphism but no other common polymorphisms (viz., m1, m2, and m3) in the risk for cervical cancer.This finding may be useful when screening for risk of cervical cancer among Northeast Thai women.<br />.

Keywords: CYP1A1; Cervical cancer; Genetic polymorphism; risk.

Figure 1

Example of Restriction Fragment Length Polymorphism (RFLP) of CYP1A1 m4 Products: BsaI enzyme was used to digest the 204-bp product of CYP1A1 m4, M is a molecular-weight size marker, the homozygous wild-type (CC) produced two bands, a 139-bp and 65-bp as shown in lanes 2, 3, 4, 5, 6 and 7, the heterozygous type (CA) produced three bands, a 204-bp, 139-bp and 65-bp as shown in lanes M and 1 and the homozygous mutant-type (AA) produced entirely 204-bp which was not detected in this study