CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study

Abstract

Background: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. Materials and Methods: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. Results: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. Conclusions: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.

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

“…The polymorphic status in the m3 locus may be specific for persons of African-American descent (Garte et al, 2001;Li et al, 2004). Our results show a lack of significant association between m1 and m2 polymorphisms and cervical cancer risk, which as in several others tudies-done among Japanese, Israeli Jewish, Polish, Chinese, and Indian populations (Sugawara et al, 2003;Gutman et al, 2009;Roszak et al, 2014;Tan et al, 2016). To contrast, significant associations between m1 and/or m2 polymorphism and increased cervical cancer risk have been documented in several populations (Tan et al, 2017;Juárez-Cedillo et al, 2007;Jain et al, 2017;Li et al, 2016;Wang et al, 2017;Ding et al, 2018), and a meta-analysis indicated that the m1 (CC) genotype was associated with an increased risk for cervical cancer among Asians and Mixed populations (Wu et al, 2013).…”

“…To date, genetic polymorphisms of human CYP1A1 have been widely studied for the susceptibility to various cancers (e.g., cancer of lung, oral, larynx, breast, thyroid, prostate, renal, cervix uteri, gastric, and colon) (Li et al, 2004;Gajecka et al, 2005;Little et al, 2006;Siraj et al, 2008;Wright et al, 2010;Li et al, 2016;Balaji et al, 2012;Agudo et al, 2014;Meng et al, 2015). Notwithstanding, to our knowledge there are no recent reports of any association between the four polymorphic loci of the CYP1A1 and cervical cancer susceptibility (Sugawara et al, 2003;Juárez-Cedillo et al, 2007;Gutman et al, 2009;Roszak et al, 2014;Abbas et al, 2014;Tan et al, 2016;Jain et al, 2017). Our aim was thus to evaluate these four polymorphic loci of CYP1A1 for the cervical cancer susceptibility among Northeast Thai women.…”

Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk

“…The main characteristics of studies included in the meta-analysis are shown in Table 1 . With respect to MspI polymorphism, 13 studies [ 10 – 13 , 15 – 18 , 20 , 31 – 34 ] (2148 cases and 2252 controls) were eligible. What needs illustration is that the study of Tan et al was performed on mixed ethnicity population, after careful assessment and discussion, we classified the Indians as Caucasians and categorized Malay and Chinese as Asian population while performing subgroup analyses.…”

“…What needs illustration is that the study of Tan et al was performed on mixed ethnicity population, after careful assessment and discussion, we classified the Indians as Caucasians and categorized Malay and Chinese as Asian population while performing subgroup analyses. [ 34 ] Therefore, 9 studies [ 10 , 15 – 18 , 20 , 32 – 34 ] (1323 cases and 1401 controls) were performed on Caucasians, and 5 studies [ 11 – 13 , 31 ] (825 cases and 851 controls) were performed on Asian population. Concerning Ile462Val polymorphism, 8 studies [ 10 , 12 , 14 , 16 , 18 , 19 , 31 , 32 ] (1466 cases and 1690 controls) were eligible.…”

“…First, the previous meta-analysis was time limited, for some recent case–control studies were conducted after its publication, especially in the past 2 years. [ 20 , 31 – 34 ] In total, our study included a total of 2148 cases and 2252 controls for MspI and 1466 cases and 1690 controls for Ile462Val; in contrast, the previous study by Sergentanis et al included 722 cases and 770 controls for MspI, 350 cases and 519 controls for Ile462Val, respectively. The sample size of our study is almost triple as large as theirs, giving a greater power to evaluate the relation.…”