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

Mayuree Wongpratate,Takafumi Ishida,Sophida Phuthong,Wannapa Ishida,Sitakan Natphopsuk

doi:10.31557/apjcp.2020.21.1.243

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.

Highlights

Cytochrome P450 1A1 (CYP1A1), an important enzyme in phase I of cytochrome P450 superfamily (CYPs), plays a key role in the detoxification of several xenobiotics (e.g., 7-ethoxyresorufin, theophylline, caffeine, and 7-ethoxycoumarin) and endogenous substances (e.g., 17β-estradiol and estrone) (Bozina et al, 2009)
Our results demonstrated a possible involvement of the CYP1A1 m4 polymorphism but no other common polymorphisms in the risk for cervical cancer.This finding may be useful when screening for risk of cervical cancer among Northeast Thai women
The genotype distributions of the m1 and m2 polymorphisms among the controls and cases were consistent with the Hardy-Weinberg equilibrium (HWE) (p>0.05); that of the m4 polymorphism among the cases deviated from the HWE (p

Summary

Introduction

Cytochrome P450 1A1 (CYP1A1), an important enzyme in phase I of cytochrome P450 superfamily (CYPs), plays a key role in the detoxification of several xenobiotics (e.g., 7-ethoxyresorufin, theophylline, caffeine, and 7-ethoxycoumarin) and endogenous substances (e.g., 17β-estradiol and estrone) (Bozina et al, 2009) In addition to these substances, CYP1A1 has potential for catalyzing environmental procarcinogens such as polycyclic aromatic hydrocarbons (PAHs), leading to generation of reactive metabolites that are highly reactive towards DNA (Androutsopoulos et al, 2009). 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

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Conclusion