CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

Abstract

CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A→G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A→G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95% CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95% CI = 0.70-2.79) with OSCC.

Association of GSTP1 Ile105Val Polymorphism and Risk of Head and Neck Cancers: A Meta-Analysis of 28 Case-Control Studies

“…Thus, the random-effect model was utilized for evaluation. In Figure 2, one can observe that 5 studies [13], [31], [36], [44], [45] may attribute to the major sources of heterogeneity. Further stratified meta-analysis is needed to perform.…”

“…2), one can observe that 5 studies are the major sources of heterogeneity [13], [31], [36], [44], [45]. In some papers, the study design included important oversights, for example, some studies used small sample sizes [36], [44], [45]. Selection bias may be another source of heterogeneity.…”

“…Selection bias may be another source of heterogeneity. Some studies used samples with highly heterogeneous ethnic origins [45], [47] or the composition of ethnicity was not clearly stated [44]. Other studies recruited control subjects from hospital-based population.…”

“…It was reported that the metabolic action of GST enzymes may differ by cancer site; the highest concentrations of GSTP1 have been observed in oral and pharyngeal tissues, and the highest concentrations of GSTM1 have been observed in laryngeal tissue, relative to the other GSTs [52]. Studies on GSTP1 polymorphism and the risk of oral cavity cancer reached controversial conclusions [13], [15], [31], [36], [45]. In this study, no positive association was found between the GSTP1 polymorphism and the risk of oral or oropharyngeal cancer.…”

Population analysis of xenobiotic metabolizing genes in South Brazilian Euro and Afro-descendants

“…, Europeans, Africans, Asians, and their mixed descendants) in case-control studies of complex diseases. With regard to cancers, these studies focus primarily on lung, breast, and head and neck tumors (Olshan et al , 2000; Gajecka et al , 2005; Yang et al , 2005; Leichsenring et al , 2006; Losi-Guembarovski et al , 2008; Torresan et al , 2008; Varela-Lema et al , 2008). …”