Debrisoquine hydroxylation in a Polish population

Kunicki, Paweł K.; Sitkiewicz, Dariusz; Borowiecka, E; Pawlik, Andrzej; Gawrońska-Szklarz, B; Sterna, Rozalia; Bielicka-Sulzyc, V.; Matsumoto, Halina; Radziwoń-Zaleska, Maria

doi:10.1007/bf00193702

Cited by 7 publications

(2 citation statements)

References 17 publications

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“…So far, two tobacco smoke components: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine, have been proposed as substrates for CYP2D6 (Crespi et al, 1991;Cholerton et al, 1994). The frequency of predicted phenotypes for our group of patients is almost identical to the frequency of phenotypes determined by pharmacogenetic methods in a healthy Polish population (EM: 58% by genotyping vs 57% by metabolite measurements, IM 37% vs 37%, PM 5% vs 6%) (Kunicki et al, 1995). Considering the CYP2D6 genotype (presence of alleles A and B), we classified the patients by the two predicted phenotypes (EM or IM and PM).…”

Section: supporting

confidence: 52%

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

Rusin¹,

Butkiewicz²,

Małusecka³

et al. 1999

Br J Cancer

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The p53 mutation spectrum can generate hypotheses linking carcinogen exposure to human cancer. Although it is well-documented that tobacco smoking is a major cause of lung cancer, the contribution of air pollution is less well-established. We determined the molecular and immunohistochemical changes ( p53 gene mutations, p53 protein accumulation and WAF1 protein expression) and genetic polymorphisms of GSTM1, CYP1A1 and CYP2D6 genes in a case series of non-small-cell lung cancers from Silesia. This region of southern Poland is highly industrialized with considerable environmental pollution. More than 50% of lung cancers (90/164) contained p53 mutations and 75% showed the combined alteration of the p53 gene and protein accumulation. Males occupationally exposed to coal-derived substances showed a relatively high frequency of squamous and large-cell carcinomas, relatively frequent mutations in codon 298 of p53 and a low frequency of p53 immunohistochemically positive tumours. Codon 298 GAG→ →TAG mutations have rarely been found in lung cancers in other populations. We found no correlation between WAF1 protein expression and mutations in the p53 gene or p53 protein accumulation. No statistically significant relationship was found between p53 mutations and GSTM1, CYP1A1, CYP2D6 genotypes. Never smokers with lung cancers from Silesia had a higher frequency of G:C→ →T:A transversions than previously reported of the p53 mutation spectrum in never smokers (6/15 vs 4/34; P = 0.06 by χ 2 ). These data are a tentative indication that occupational and environmental exposure to polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, in polluted air contributes to the molecular pathogenesis of lung cancer in never smokers. © 1999 Cancer Research Campaign

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Section: supporting

confidence: 52%

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

Rusin¹,

Butkiewicz²,

Małusecka³

et al. 1999

Br J Cancer

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“…Previous Polish population studies have been based on smaller material. Kunicki et al [13] found 5.8% PM of debrisoquine in 156 phenotyped persons, Gawronska-Szklarz et al [14] revealed 9.6% PM in 145 genotyped persons, and our preliminary results showed 8.8% PM in 160 phenotyped persons [15]. The frequency distributions of CYP2D6*1, CYP2D6*3, and CYP2D6*4 alleles (75.7%, 1.3%, and 23.0%, respectively) in our study are similar to those in other white populations.…”

Section: Discussionmentioning

confidence: 98%

CYP2D6 extensive, intermediate, and poor phenotypes and genotypes in a Polish population

Niewiński

Orzechowska-Juzwenko

Hurkacz

et al. 2002

European Journal of Clinical Pharmacology

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Of 300 participants in the study 25 (8.3%) were classified as poor metabolizers, 44 (14.7%) as intermediate metabolizers, and 231 (77%) as extensive metabolizers of sparteine. The frequency of CYP2D6*1, CYP2D6*3, and CYP2D6*4 alleles among the genotyped 300 persons was 75.7%, 1.3%, and 23.0%, respectively. The frequency of CYP2D6 deficient genotypes in a Polish population (8.0%) was similar to phenotyping results. The comparison of phenotype and genotype in 60 randomly selected individuals showed a good concordance of the obtained results. CONCLUSIONS. The frequencies of poor metabolizers for CYP2D6 phenotype (8.3%) and genotype (8.0%) in a Polish population from the southwestern region are in concordance and compare well with most results of poor oxidation metabolizers in other white populations.

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N-Acetylation and hydroxylation polymorphisms in type II diabetics with microvascular disturbances

Gawrońska-Szklarz¹,

Górnik²,

Pawlik³

et al. 1997

European Journal of Clinical Pharmacology

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The N-acetylation and hydroxylation (CYP2D6) genetic polymorphisms were assessed in 43 healthy subjects and in 84 type II (non-insulin-dependent) diabetics. The proportions of slow and fast acetylators as well as poor and extensive metabolisers in a group of diabetics suffering from microvascular disturbances (nephropathy, retinopathy and neuropathy) were compared with the control group and with diabetics without such complications. Sulphadimidine was used as a probe for polymorphic acetylation and debrisoquine for CYP2D6. Debrisoquine and its 4-OH metabolite were assayed by means of HPLC, and sulphadimidine using a modified Bratton-Marshall procedure. The frequency of the slow phenotype (63%) was significantly higher in diabetics with microvascular disturbances than in patients without diabetic complications (P < 0.005). In patients with type II diabetes (84), only the extensive phenotype of hydroxylation was observed.

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Debrisoquine hydroxylation in a Polish population

Cited by 7 publications

References 17 publications

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

CYP2D6 extensive, intermediate, and poor phenotypes and genotypes in a Polish population

N-Acetylation and hydroxylation polymorphisms in type II diabetics with microvascular disturbances

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