Cytochrome P450s are heme-containing enzymes that are involved in the synthesis and metabolism of various molecules and chemicals within cells. These enzymes are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Cytochrome P450 CYP1A1, located on chromosome 15q24.1, is one of the three members of the CYP1 family. It localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The transcriptional activation of the CYP1A1 gene is mediated by the binding of environmental pollutants and inhalation chemicals. CYP1A1 enzyme may function as a carcinogen-detoxication enzyme. It is able to metabolize some PAHs to carcinogenic intermediates.
The CYP1A1 gene spans approximately 6 kb within the genomic DNA with six coding exons. It has been found that CYP1A1 variants are associated with lung cancer risk.
[See: Saudi Arabia > Bu et al., 2004].
Bu et al., (2004) studied the frequencies of alleles and genotypes for CYP1A1, NAT2, GSTs, MTHFR, MTR (MS), and NQO*1 genes among Arabs. Of the studied group, 95% were from Saudi Arabia, and 5% were from Jordan, Syria, Lebanon, and Yemen. The mean age was 37 years, and male to female ratio was (25:1). Three polymorphisms in the CYP1A1 gene were analyzed: T3801C, A2455G, and C2453A. Allelic frequencies among the studied group were 20% for 3801C, 7% for 2455G, and 19% for 2453A.
Al-Achkar et al. (2014) we investigated the associations of polymorphisms in the cytochrome P450 gene (CYP1A1) and the glutathione S-transferase genes (GSTM1 and GSTT1) with chronic myelogenous leukemia (CML). A total of 126 patients with CML and 172 healthy volunteers were genotyped. Logistic regression analyses showed significant risk of CML associated with CYP1A1 Val allele [odds ratio (OR) 3.3, 95% confidence intervals (CI) 1.96-5.53], (p < 0.0001) while CYP1A1 Val/Val homozygotes were observed only in the CML patients. There was statistically significant difference in the frequency of GSTM1 and GSTT1 null genotypes. The GSTT1-null genotype was slightly higher in 27% of CML cases and 17% of controls (OR 1.98, 95% CI 1.12-3.5) (p < 0.020). The GSTM1 null was higher in 43% of CML cases and 23% of controls (OR 2.55, 95% CI 1.54-4.22) (p < 0.00024). Individuals carrying the CYP1A1 Ile/Val (AG) and GSTM1 null genotype have 9.9 times higher risk to be CML than those carrying CYP1A1 Ile/Ile (AA) and GSTM1 present genotype (OR 9.9, 95% CI 2.7-36.3) (p < 0.0001). Al-Achkar et al. (2014) concluded that the association of the GSTM1 null genotype, either alone or in combination with GSTT1 null, with CYP1AI heterozygous leads to the CML risk.
[See also: Saudi Arabia > Bu et al., 2004].