Study the polymorphism of CYP3A5 and CYP3A4 loci in Iranian population with laryngeal squamous cell carcinoma
Organ Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Molecular Biology Reports
(Impact Factor: 2.02).
03/2011; 38(8):5443-8. DOI: 10.1007/s11033-011-0699-0
Cancer reflects a complicated network of interactions between genes and environmental factors. Cytochrome P450 (CYP) is a multi-gene superfamily participating in the metabolism of xenobiotics. The aim of our study was to examine whether polymorphisms in the CYP enzyme genes affect the risk of developing larynx squamous cell carcinoma (SCC). Polymorphism of CYP3A5 and CYP3A4 genes were investigated in 50 patients with laryngeal SCC and 100 control subjects by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). In patients the CYP3A5 3/3 and 1/3genotypes were detected in 92% and 8% respectively. There was no relation between genotype, allele frequency and grade/stage of tumor. In control group, the frequency of CYP3A5 3/3 and CYP3A5 1/3 genotype were 98% and 2% respectively. There was no significant difference in genotype and allele frequency of this gene between patient and control group. In respect of CYP3A41A/B, people in both patient and control groups had the same genotype of CYP3A41A/1A. In this study, the CYP gene variants were not associated with increased risk of laryngeal SCC. Study on the other genetic factors which are involved in activation/detoxication of procarcinogenes, such as CYP1A1, CYP1B1, CYP2E1 and gluthation S transferase is recommended.
Available from: Amir Jalali
- "Population N * CYP3A5 genotype frequency(%) P-value ** References *3/*3 *3/*1 *1/*1 (G/G) (G/A) (A/A) Asian Iranian(Ahvaz city) 200 198 0 2 This study Iranian(shiraz city) 100 98 2 0 0.082  Chinese(2005) 302 190 90 2 <0.0001  "
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ABSTRACT: Background: Polymorphisms of different gene have been reported to be associated with cancer including breast cancer. Hospitalization rate for breast cancer has increased over the years in Iran. Aim: The aim of this study was to examine whether polymorphisms in the CYP3A4 and CYP3A5 genes affect the risk of developing breast cancer. Subjects and methods: The genotype distribution and allele frequencies of four CYP3A4*1A, CYP3A4*1B, CYP3A5*1 and CYP3A5*3 single-nucleotide polymorphisms were determined in 250 subjects from the general population in Ahvaz city (southwest of Iran) including 200 healthy subjects and 50 individuals affected with breast cancer. Results and conclusion: The genotype frequency of CYP3A4*. 1A/*. 1A (A/A) in both case and control groups was 100%; however, there was no subject with either CYP3A4*. 1A/*. 1B (A/G) or CYP3A4*. 1B/*. 1B (G/G) genotype. For CYP3A5 gene, CYP3A5*. 3/*. 3mutant homozygote genotype frequency was found to be 99% (. n=. 198) and 98% (n = 49) in control and patient groups respectively. CYP3A5*. 1/*. 1 wild-type genotype was calculated to be 1% (n = 2) in the control group and 2% (n = 1) in the case group. No. CYP3A5*. 1/*. 3 heterozygote genotype was detected in the both groups. The results showed that there was no association between breast cancer, CYP3A5 (P-value = 0.561) and CYP3A4 allele distribution.
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ABSTRACT: Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Variability in TPMT activity is mainly due to genetic polymorphism. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G) were determined in an Iranian population from south of Iran (n = 500), using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. Four hundred seventy four persons (94.8%) were homozygous for the wild type allele (TPMT*1/*1) and twenty five people were TPMT*1/*3C (5%). One patient was found to be heterozygous in terms TPMT*1 and *2 alleles with genotype of TPMT*1/*2 (0.2%). None of the participants had both defective alleles. The TPMT*3C and *2 were the only variant alleles observed in this population. The total frequency of variant alleles was 2.6% and the wild type allele frequency was 97.4%. The TPMT*3B and *3A alleles were not detected. Distributions of TPMT genotype and allele frequency in Iranian populations are different from the genetic profile found among Caucasian or Asian populations. Our findings also revealed inter-ethnic differences in TPMT frequencies between different parts of Iran. This view may help clinicians to choose an appropriate strategy for thiopurine drugs and reduce adverse drug reactions such as bone marrow suppression.
Available from: Mehrzad Banihashemi
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