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.

Genetic Polymorphisms of Pesticide-Metabolizing Enzymes and Transporters in Agricultural Workers and Thyroid Hormone Levels

“… 26–29 For example, the allele frequencies of CYP1A1 rs1048943 (0.21 for chemical workers and 0.31 for organic workers) and rs4646903 (0.49 for chemical workers and 0.42 for organic workers) found in this study were similar to those in another report of a Thai population (0.29 and 0.50, respectively). 26 For two CYP1A2 SNPs, our findings were in agreement with the minor allele frequency found in a Korean population (0.35 for rs762551 and 0.25 for rs2069514). 27 CYP2E1 is an enzyme that functions in the metabolic pathways of synthetic pesticides.…”

Pleiotropic Functions of Cytochrome P450 Monooxygenase-Derived Eicosanoids in Cancer

“…T3801C (rs4646903) and T3205C are situated in the 3′ noncoding region while A2455G (rs1048943) and C2453A are ascertained in exon 7, which results in the transition of isoleucine to valine on codon 462 and threonine to asparagine on codon 461, respectively (Li et al, 2004). The monomorphism of T3205C locus was reported in Indians (Singh et al, 2007), Americans (San Francisco) (Hirata et al, 2008), and Northeast Thai women (Wongpratate et al, 2020). Among several populations, the polymorphisms of T3801C and/ or A2455G were reported to associate significantly with the increased risk in cervical cancer (Juarez-Cedillo et al, 2007;Li et al, 2016;Jain et al, 2017;Wang et al, 2017;Ding et al, 2018).…”

“…However, there is a lack of significant association between T3801C and A2455G polymorphisms and cervical cancer risk in Chinese, Japanese, Israeli Jewish, Polish, Indian, and Thai populations (Sugawara et al, 2003;Gutman et al, 2009;Roszak et al, 2014;Tan et al, 2016;Wongpratate et al, 2020). The A allele of C2453A is associated with the risk of lung cancer (Gallegos-Arreola et al, 2008;Ezzeldin et al, 2017), laryngeal squamous cell carcinoma (Gajecka et al, 2005), thyroid cancer (Siraj et al, 2008), and cervical cancer (Wongpratate et al, 2020), but not associated with breast (Li et al, 2004;Singh et al, 2007;Amrani et al, 2016), colorectal (Little et al, 2006), or gastric cancer (Agudo et al, 2006).…”

Frequency of CYP1A1*2A polymorphisms and deletion of the GSMT1 gene in a Peruvian mestizo population

“…Cancer is a priority disease for national and global public health; being the second cause of death worldwide. The year 2020 registered 19.3 million new cases and 9.9 million deaths related to cancer, many of these cancers have an environmental component (Sung et al 2021); in Peru, mortality from cancer in 2018 was 33,098 deaths (17,039 women The CYP1A1, CYP2C19, CYP2D6 and CYP17 genes that encode their respective isoenzymes are associated with different types of cancer (Lee et al 2006), by participating in the phase I metabolism of procarcinogens [polycyclic aromatic hydrocarbons (benzopyrene), arylamines, N-nitrosamines and dioxins] forming reactive metabolites that produce DNA adducts (Lee et al 2006;Attia 2010;Jin et al 2011;Rahal et al 2013;Acevedo et al 2014;Wongpratate et al 2020); of them, the CYP1A1 gene (Santes-Palacios et al 2016), has greater susceptibility to various types of cancer (Wongpratate et al 2020), such as gastric, colorectal, buccal, esophageal, laryngeal, mammary, cervix, lung , thyroid, prostate and kidney (Jin et al 2011;Balaji et al 2012;Meng et al 2015;Li et al 2016;Ding et al 2017).…”

“…The GSTM1*0 variant is the product of a homozygous deletion, due to an unequal recombination between two highly conserved regions of 4.2 kb that are located at the 5' and 3' ends of the gene respectively, generating a null allele that expresses an enzyme without activity (Board and Menon 2013;Rosero et al 2016;Heredia et al 2017), which leads to genomic instability that predisposes to various types of cancer (Heredia et al 2017;Satinder et al 2017). Figure 1 outlines the action of the CYP1A1 enzyme (expressed by the CYP1A1 gene) on benzopyrene (Route A), which converts it into a bioactive metabolite (7,8-dihydroxy-9,10-oxy-benzopyrene) that binds to the guanine of DNA generating the benzopyrene guanine adduct that induces mutagenic and carcinogenic processes (Lee et al 2006;Acevedo et al 2014;Wongpratate et al 2020); at the same time, the mechanism of conjugation of 4,5-benzopyrene epoxide (Route B) and 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro benzopyrene (Route C) is represented by action of reduced glutathione (GSH g-Glu-Cys-Gly) which is expressed by GSTM1; additionally, GSH conjugates different reactive oxygen species (ROS), protecting cells from cytotoxic effects and oxidative stress (Board and Menon 2013;Usategui-Martín et al 2014;García-Martínez et al 2017).…”