Abstract

BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated.

PATIENTS AND METHODS: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Results and

CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004).

Abstract

Nephrolithiasis is a complex disease and many gene polymorphisms have been associated with stone formation. In this study we aimed to investigate another possible relationship between E-cadherin gene (CHD1) 3′-UTR C/T polymorphism and calcium oxalate nephrolithiasis in the Turkish population. Study population was composed of 143 patients with nephrolithiasis and 158 control subjects. CHD1 3′-UTR C/T polymorphism was analysed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Genotype distribution of the investigated polymorphism was not deviated from Hardy-Weinberg equilibrium (HWE) in patients and control subjects (P > 0.05). C allele frequency was 85.7 and 85.1% in patients and controls, respectively (P = 0.836). Genotype distributions of the CHD1 3′-UTR C/T polymorphism among patients were also not significantly different from those among control subjects (P = 0.636). Our results showed that there is no association between the CHD1 gene 3′-UTR C/T polymorphism and nephrolithiasis in our population.

Abstract

The most well-known metabolic pathways from ethanol to acetaldehyde include alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system that involves cytochrome P450 2E1 (CYP2E1). Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH). The genetic variation of ADH1B, ALDH2, and CYP2E1 is different among racial populations and cause difference in elimination rates of alcohol. The aim of this study was to determine the polymorphisms of ADH1B (rs1229984; Arg47His), ALDH2 (rs671; Glu487Lys), CYP2E1*6 (rs6413432; T7632A), and CYP2E1*7B (rs6413420; G-71T) in unrelated healthy Turkish population and compare it with other populations. ADH1B and ALDH2 polymorphisms were analyzed with an allele-specific polymerase chain reaction (PCR) assay, and CYP2E1*6 and CYP2E1*7B polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. ADH1B polymorphism analysis yielded the genotype distribution as 83.9% ADH1B*1/1 and 16.1% ADH1B*1/2, and no individuals with ALDH2*1/2 and ALDH2*2/2 genotypes were found in Turkish population. The genotype frequencies for CYP2E1*6 polymorphism were found as 85.3% for homozygote common, 14.1% for heterozygote, and 0.6% for homozygote uncommon. For CYP2E1*7B polymorphism, the genotype frequencies were determined to be 86.5% G/G, 13.5% for G/T; however, no individuals with homozygote uncommon genotype were detected. According to our study results, the genotype distributions of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B in Turkish population were similar compared with Caucasian and some European populations, whereas differed significantly from East Asian populations. This study may be useful in epidemiological studies of the influence of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B polymorphisms on diseases, including several types of cancer related to alcohol consumption and alcohol dependence. Copyright © 2010 Elsevier Inc. All rights reserved.

Abstract

In this study, we aimed to investigate a possible association of the COX-2 polymorphisms with the risk of developing lung carcinoma. COX-2 (-765G–>C; -1195A–>G) gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 118 healthy individuals and 231 patients with lung carcinoma. The present study was the first that addressed the role of the COX-2-765G–>C and -1195A–>G polymorphisms in lung carcinoma in Turkish population. In the present study, we found that the frequencies of GG, CC, and CG genotypes of COX-2-765G–>C and AA, GG, and AG genotypes of -1195A–>G in our control group were 0.22, 0.22, 0.55 and 0.59, 0.0, 0.40, respectively. These frequencies in patient group were 0.34, 0.07, 0.58 and 0.74, 0.04, 0.24, respectively. There were statistically significant differences in COX-2-765G–>C (P = 0.0002) and -1195A–>G genotypes (P = 0.007) between the controls and patients. We found that individuals carrying -765 GG genotype and -765 G allele of COX-2 or 1195 AA genotype of COX-2 and -765G: -1195A haplotype had an increased risk for the development of lung carcinoma. In contrast, individuals with -765 CC, -1195 AG genotypes and -1195 G allele of COX-2 seem to be protective from lung carcinoma. We suggest that the COX-2-765G–>C and -1195A–>G genotypes may be a risk factor for lung carcinoma.