CYP2E1 gene polymorphism and ovarian cancer risk in the Yakut population

The CYP2E1 gene polymorphism has been studied in Yakut women with ovarian cancer and without cancer. The two groups have been found to substantially differ in the frequency of the CYP2E1* 1D allele (with a 96-bp insertion in the promoter region of the gene): it is more frequent in healthy women (16.3 versus 7.4%, P = 0.007).     

CYP1A1*2 and CYP1A1*3 polymorphisms cosegregate in the Indian population

Several ethnic groups have been genotyped for polymorphisms at the CYP1A1 gene locus that encodes the enzyme that catalyzes the initial step in the metabolism of polycyclic aromatic hydrocarbons. Two of the CYP1A1 polymorphisms, namely, CYP1A1*2 and CYP1A1*3 are reported to cosegregate among the Japanese and to a lesser extent in Caucasians, but not in people of African descent. In the absence of such information in the Indian population, the frequency of the CYP1A1*2 polymorphism was determined in this study, using DNA samples from 649 ethnic Indians who had been earlier genotyped for the CYP1A1*3 polymorphism. Analysis of the combined genotype data revealed that the two polymorphisms cosegregate in the Indian population.     

Lack of association between prohibitin 3' untranslated region C-->T polymorphism and breast cancer in a Turkish population

The 3' untranslated region (3'UTR) of the prohibitin gene has a positive effect on arresting cell proliferation between G1 and S phases and inhibits DNA synthesis. A C-to-T transition within this region creates a variant that alters mRNA function and has been shown to be associated with an increased breast cancer risk among young North Americans who are under 50 years and have at least one first-degree relative with breast cancer. We carried out a population-based case-control study to assess whether this association exists in Turkish women. We examined 106 breast cancer patients and 154 healthy controls by PCR and restriction fragment length polymorphism analysis. In the prohibitin 3'UTR, we did not detect a difference in CT/TT genotype frequency (p = 0.694; odds ratio [OR], 1.106; 95% confidence intervals [CI], 0.659-1.86) or in C/T allele frequency (p = 0.850; OR, 1.043; 95% CI, 0.667-1.62) between the all breast cancer patients and the controls. The results did not change in subgroups defined by age or family history. Hence our results do not lend support to the hypothesis that this polymorphism contributes to risk of breast cancer. The prohibitin T variant is not associated with the risk of breast cancer in Turkish women.     

CYP1A1 genetic polymorphisms, tobacco smoking and lung cancer risk in a French Caucasian population

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CYP1A1 genetic polymorphisms,tobacco smoking and lung cancer risk in a French Caucasian population

The CYP1A1 gene encoding for an enzyme involved in the metabolic activation of important tobacco carcinogens could be implicated in smoking-induced lung cancer. Given the strong association between tobacco smoking and lung cancer, the effect of tobacco smoke exposure has to be taken into account when studying the potential association between lung cancer and CYP1A1 genotypes. The effect of two CYP1A1 genetic polymorphisms (Mspl and IIe-Val) on lung cancer risk were evaluated using peripheral blood DNA from 150 lung cancer patients and 171 controls. The Mspl sitepresent allele was found among 19.3% of both cases and controls and the variant allele Val among 6.7% of cases and 8.8% of controls. Lung cancer risks associated with the Mspl site-present allele (OR= 0.9; 95%Cl: 0.5-1.8) or with the Val allele (OR= 0.8; 95%Cl: 0.3-1.9) were not increased after adjustment for tobacco and asbestos exposures. These results persisted when analyses were stratified on smoking status, daily consumption of tobacco or duration of smoking. Similar findings were obtained when squamous cell or small cell carcinomas were studied separately. This study thus suggests a minor role for the known CYP1A1 gene polymorphisms in predisposition to lung cancer among Caucasian populations.     

CYP1A1 and CYP2D6 polymorphism and risk of lung cancer in a North Indian population

This case–control study was conducted to examine the association between the CYP1A1 and CYP2D6 genotypes and lung cancer risk among North Indians. The estimated relative risk for lung cancer associated with the CYP1A1 Val/Val allele was 2.68, and was four-fold when cases with small cell lung cancer (SCLC) were considered alone. With regard to the metabolism of debrisoquine, no poor metabolizers were found amongst the subjects. The odds ratio of risk with the heterozygous extensive metabolizer (HEM) genotype was 1.5. However, in the presence of at least a single copy of the variant CYP1A1 MspI allele and the CYP2D6 HEM genotype, the risk was two-fold for squamous cell carcinoma (SQCC). When the CYP1A1 Val/Val and CYP2D6 HEM genotypes were taken together, the risk for SCLC was four-fold. Stratified analysis indicated an interaction between bidi smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. Heavy smokers (Brinkman index>400) with Val/Val genotypes were at a very high risk of developing lung cancer (odds ratio 29.30, 95% confidence interval 2.42–355, p=0.008). Heavy smokers with CYP1A1 MspI (CYP1A1*1/2A or CYP1A1*2A/*2A) genotype had a seven-fold risk for SCLC compared with non-smokers. This study is the first to be carried out on a North Indian population, and, although small, suggests that CYP1A1 and CYP2D6 polymorphisms might have a role in determining the risk for lung cancer and should be investigated further.     

CYP1A1 and CYP2D6 polymorphism and risk of lung cancer in a North Indian population.

This case-control study was conducted to examine the association between the CYP1A1 and CYP2D6 genotypes and lung cancer risk among North Indians. The estimated relative risk for lung cancer associated with the CYP1A1 Val/Val allele was 2.68, and was four-fold when cases with small cell lung cancer (SCLC) were considered alone. With regard to the metabolism of debrisoquine, no poor metabolizers were found amongst the subjects. The odds ratio of risk with the heterozygous extensive metabolizer (HEM) genotype was 1.5. However, in the presence of at least a single copy of the variant CYP1A1 MspI allele and the CYP2D6 HEM genotype, the risk was two-fold for squamous cell carcinoma (SQCC). When the CYP1A1 Val/Val and CYP2D6 HEM genotypes were taken together, the risk for SCLC was four-fold. Stratified analysis indicated an interaction between bidi smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. Heavy smokers (Brinkman index>400) with Val/Val genotypes were at a very high risk of developing lung cancer (odds ratio 29.30, 95% confidence interval 2.42-355, p=0.008). Heavy smokers with CYP1A1 MspI (CYP1A1*1/2A or CYP1A1*2A/*2A) genotype had a seven-fold risk for SCLC compared with non-smokers. This study is the first to be carried out on a North Indian population, and, although small, suggests that CYP1A1 and CYP2D6 polymorphisms might have a role in determining the risk for lung cancer and should be investigated further.     

CYP17 gene polymorphism and prostate cancer susceptibility in a Tunisian population

Prostate cancer (PCa) formation has been reported to be associated with androgen. Two key steps in the sex steroid synthesis are mediated by the enzyme cytochrome P450c 17α which is encoded in the CYP17 gene. The A2 allele of the CYP17 gene has been thought to be associated with increased functional activity of this steroidogenic enzyme. Consequently, the A2 allele has been examined as a biomarker of individual susceptibility to hormone-related diseases among men. We prospectively assessed the association between the A2 allele of CYP17 and PCa risk among 125 cases and 125 controls in a case–control study. Our aim was to investigate whether a polymorphism of CYP17 gene could be used as a genetic marker for associating PCa. The result revealed a significant association between the CYP17 polymorphic genotypes and PCa. Therefore, CYP17 gene polymorphism is likely contributed to the pathogenesis of PCa but not to disease severity.     

Identification of genetic polymorphisms of CYP2S1 in a Finnish Caucasian population

CYP2S1 is a recently discovered member of the cytochrome P450 (CYP) gene superfamily. Interestingly, even though the DNA sequence identifies it as the sole member of the new CYP2S family, CYP2S1 exhibits many features typical to CYP1 family members, e.g. dioxin-inducibility mediated by the aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, CYP2S1 metabolises some aromatic hydrocarbons as well as cellular substances. These characteristics, together with a wide extrahepatic tissue distribution, suggest that CYP2S1 may have an important role in both exogenous and endogenous metabolism. This is the first study characterising CYP2S1 alleles and naming them with the recommended CYP allele nomenclature. We used denaturing gradient gel electrophoresis (DGGE) and direct sequencing to investigate genetic variation of CYP2S1 in 100 male Finnish Caucasians. Those exons in which variation was found were examined in subsequent 100 subjects. The coding region of all of the nine exons, as well as a 449 bp fragment of the proximal promoter region, was analysed. This systematic investigation revealed eight single nucleotide polymorphisms (SNPs), which comprise nine different variant alleles (haplotypes), in addition to the wild-type allele. Seven of the SNPs occurred in the protein-coding areas and one in the proximal 3' untranslated region (3'UTR). Two of these sequence variations (10347C > T and 13106C > T) result in non-conservative amino acid substitutions, i.e. Arg380Cys and Pro466Leu, respectively. The respective allelic variants, CYP2S1*2 ([10347C > T]) and CYP2S1*3 (13106C > T; 13255A > G]), occurred in our study population at frequencies of 0.50 and 3.75%, respectively. The most common of the variant alleles was CYP2S1*1H (23.8%), harbouring a 13255A > G substitution located in the 3'UTR.     

Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence

Research has shown that genetic polymorphisms in biotransformation enzymes, such as CYP1A1 and GSTM1, are related to a greater or lesser susceptibility to various cancers. We made an analysis of CYP1A1m1 SNP and GSTM1 null genotypes in a family group (71 members) related by consanguinity who had an unusually high incidence of cancer and a high frequency of smokers. There were no significant differences in genotype frequencies in this family when compared to data for Brazilian populations. Possibly, the high incidence of cancer in this sample is associated with smoking and/or other factors not detected in this survey.     

Genetic polymorphism of the CYP1A1, CYP2E1, GSTM1 and GSTT1 genes and lung cancer susceptibility in a north Indian population

The present study investigates in a experimental system in vitro the relationship between the non-enzymatic (ascorbate-Fe2+) and enzymatic (NADPH) lipid peroxidation in rat liver microsomes and nuclei. Chemiluminescence was measured as cpm/mg protein during 180 min at 37 degrees C. Approximately 50-55% of the fatty acids located in rat liver microsomes and nuclei are polyunsaturated with a prevalence of C18:2 n6 and C20:4 n6. The values of total light emission during the non-enzymatic and enzymatic lipid peroxidation were highest in microsomes than in nuclei. A significant decrease of C20:4 n6 and C22:6 n3 in rat liver microsomes and nuclei was observed during the lipid ascorbate-Fe2+-dependent peroxidation, whereas a significant decrease of C20:4 n6 in rat liver microsomes was observed during enzymatic lipid peroxidation. Over the time course studies, analysis of chemiluminescence in microsomes and nuclei demonstrated that the lipid peroxidation in the presence of ascorbate-Fe2+ reach a maximum at 50 and 30 min, respectively, whereas in the presence of NADPH it reachs a maximum at 20 min in both organelles. In liver microsomes and nuclei the peroxidizability index (pi) which indicates the degree of vulnerability to degradation of a selected membrane showed statistically significant differences between control versus ascorbate-Fe2+ when microsomes or nuclei were compared. Our results indicate that non-enzymatic (ascorbate-Fe2+) and enzymatic (NADPH) lipid peroxidation are operative in rat liver microsomes and nuclei but the sensitivities of both organelles to lipid peroxidation evidenced by chemiluminescence was greater in the presence of ascorbate-Fe2+ when compared with NADPH.     

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which significantly promote proliferation of cancer cells in vitro and in vivo. We looked for a possible association between human CYP2C19*3 gene polymorphism and breast cancer in the Chinese Han population. In a Chinese Han case-control study of breast cancer patients (N = 600) and age- and gender-matched healthy controls (N = 600), we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in breast cancer patients than in control subjects (6.67 vs 3.00%; P = 0.003). The odds ratio for carriers of AG + AA genotype for breast cancer was 2.31 (95% confidence interval = 1.27-4.43). Among patients, estrogen receptor, tumor size, histologic grade, presence of primary lymphonode metastases, progesterone receptor positivity, and age at diagnosis were not found to be significantly associated with CYP2C19*3 genotypes (all P > 0.05). We conclude that the CYP2C19*3 gene polymorphism is associated with breast cancer risk in Chinese Han women.     

CYP1A1 *2B and *4 polymorphisms are associated with lung cancer susceptibility in Mexican patients

BACKGROUND: CYP1A1 is a gene involved in the high aryl hydrocarbon hydroxylase -inducible phenotype, which is a genetically-determined variation among individuals that has been associated with lung cancer risk. More specifically, CYP1A1 *2B and *4 polymorphisms have been associated with high susceptibility to lung cancer among cigarette smokers. MATERIALS AND METHODS: DNA was obtained from blood samples and we studied by PCR-RFLP the distribution of CYP1A1 *2B (n=248) and *4 (n=222) polymorphisms in healthy controls and 222 lung cancer patients from a Mexican population. RESULTS: Comparisons between groups showed an increased risk for lung cancer patients of *2B/*2B (18%; OR 7.6; 95% CI 3.0-19.2) and *4/ *4 genotypes (15%; OR 11.45; 95% CI 2.19-59.85) compared to the control group (1% for *2B/ *2B and 4.4% for *4/ *4). A significant association between lung cancer and homozygous *2B/ *2B passive smokers and *4/*4 ever (cigarettes) and passive smokers was also observed (p<0.05). Multivariate analysis revealed an increased risk for the *2B/*2B genotype (OR 6.83), as well as for *4/*4 (OR 28.8). CONCLUSION: The results of the study indicate a significant association between *2B/*2B and *4/*4 genotypes and the risk of developing lung cancer among Mexicans.     

Lack of association between p53 codon 72 polymorphism and endometrial cancer: a meta-analysis

Background: It has been suggested that the p53 tumor suppressor gene Arg72Pro polymorphism is associated with endometrial cancer. However, results have been inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and endometrial cancer. Methods: An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assessed by pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Nine published studies, including 829 endometrial cancer cases and 1387 controls, were identified. The overall results suggested that the variant genotypes were not associated with the endometrial cancer risk in all genetic models (additive model: OR 1.027, 95% CI 0.893–1.18, P = 0.71; recessive model: OR 1.099, 95% CI 0.802–1.507, P = 0.556; dominant model: OR 1.013, 95% CI 0.842–1.219 P = 0.89). Similarly, the results were negative in subgroup analyses for ethnicity (Caucasian, Asian). Conclusion: This meta-analysis suggests that p53 codon 72 polymorphism is not associated with increased risk of endometrial cancer, especially in Caucasians and Asians. To validate the association between this polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed.     

Lack of association between Y-chromosomal haplogroups and prostate cancer in the Korean population

The Y chromosome has recently been suggested to have an association with prostate cancer risk in human populations. Since this chromosome is haploid and lacks recombination over most of its length, haplotypes constructed from binary markers throughout the chromosome can be used for association studies. To assess the possible Y-chromosomal contribution to prostate cancer risk, we have therefore analyzed 14 Y-chromosomal binary markers in 106 prostate cancer cases and 110 controls from the Korean population. In contrast to previous findings in the Japanese population, no statistically significant difference in the distribution of Y-chromosomal haplogroup frequencies was observed between the case and control groups of Koreans. Thus, our data imply that the previously reported associations between Y-chromosomal lineages and a predisposition to, or protection against, prostate cancer might be explained by statistical fluctuations, or by genetic effects that are seen only in some environments.     

NFKB1 insertion/deletion promoter polymorphism increases the risk of advanced ovarian cancer in a Chinese population

Ovarian cancer is the leading cause of death among all gynecological cancers. This is mainly attributed to its frequent presentation at an advanced stage (International Federation of Gynecology and Obstetrics stage III-IV). Nuclear factor-kappaB (NF-κB) is critically involved in the carcinogenesis and development of ovarian cancer. A functional insertion/deletion polymorphism (-94 ins/del ATTG) in the promoter region of the NFKB1 gene, which encodes the p50 subunit of the NF-κB protein, has been recently identified and shown to increase the susceptibility to many diseases. The purpose of this study was to explore the association between this polymorphism and the risk of advanced ovarian cancer in a Chinese population. A total of 179 advanced ovarian cancer patients and 223 healthy controls were recruited into this study. Genotypes were determined using polymerase chain reaction-capillary electrophoresis method. The insertion increased the risk of advanced ovarian cancer (odds ratio?=?2.111, 95% confidence intervals?=?1.125-3.961, p?=?0.019 for heterozygote insertion, and odds ratio?=?2.656, 95% confidence intervals?=?1.397-5.051, p?=?0.002 for homozygote insertion) compared with homozygote deletion. Similar results were seen in age-adjusted analyses (p?相似文献   

Lack of association between pro-inflammatory genotypes of the interleukin-1 (IL-1B -31 C/+ and IL-1RN *2/*2) and gastric cancer/duodenal ulcer in Korean population

IL-1beta is a pro-inflammatory cytokine with multiple biological effects and is a potent inhibitor of gastric acid secretion, and IL-1RN has been shown to be associated with enhanced IL-1beta production in vitro. Recently, it was reported that the pro-inflammatory genotypes, IL-1B -31 C/+ and IL-1RN *2/*2, were associated with an increased risk of gastric cancer in a Caucasian population. We tested the association between the polymorphisms and 190 gastric cancer, 117 duodenal ulcer, and 172 healthy subjects as controls in the Korean population. The allele frequency of IL-1B -31 C was more prevalent in Korean (51%) than in Caucasian (30%), while the frequency of IL-1RN *2 allele was less in Korean (6%) than in Caucasian (27%). Using the IL-1B TT genotype as a reference group, the CC genotype was not associated with an increased risk of gastric cancer or duodenal ulcer in the Korean population (odds ratios (OR)=0.90, 95% confidence interval (CI)=0.50-1.64; OR=0.72, 95% CI=0.36-1.46, respectively). Similarly, IL-1RN*2 was not a risk genotype for either gastric cancer or duodenal ulcer. No association was recognized on the haplotype analysis of the two genes, either. Our results did not support the previous report that IL-1B -31 C/IL-1RN*2 polymorphisms were associated with an increased risk of gastric cancer. The lack of association with duodenal ulcer also suggested that the polymorphisms were not directly related to the acid-secreting capability.     

Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance in coronary artery disease patients among Tamilian population

Clopidogrel is an antiplatelet drug. It is used for the treatment as well as for the prophylaxis of coronary artery disease. Clopidogrel resistance is an emerging problem in clinical settings. The aim of the present study was to evaluate the effect of CYP3A5*3 genetic polymorphism on clopidogrel resistance. One hundred and forty-seven patients from outpatient Department of Cardiology on 75 mg/day of clopidogrel as maintenance dose were recruited from April 2010 to July 2011. All subjects gave written informed consent to participate in the study. DNA extraction was performed using phenol chloroform extraction procedure and genotyping by standard Taqman based RT-PCR method. Platelet aggregation was done at the end of 7th and 14th day by using chronolog lumi Aggregometer which is expressed as impedance in ohms. Impedance values of >5 ohms at the end of 6 min were considered as clopidogrel resistance. Subjects (N = 147) were analysed for CYP3A5*3 polymorphism, of which 49 (33 %) were found to be clopidogrel resistant. Homomutants of CYP3A5*3 gene had 2.78 (0.97–7.98; p < 0.05) fold risk and heteromutants had 2.4 (0.93–6.46; p < 0.05) fold risk of developing clopidogrel resistance. Carriers of defective allele G of CYP3A5*3 had higher propensity to cause clopidogrel resistance with an odds ratio of 1.63. Variant alleles and genotypes of CYP3A5*3 polymorphism contributed significantly to clopidogrel resistance with a higher odds ratio. Thus, pharmacogenomics paves way for the emergence of stratified medicine in clopidogrel therapy and personalised pharmacotherapy in ischaemic heart disease.     

Interaction between CYP 2C19*3 polymorphism and smoking in relation to laryngeal carcinoma in the Chinese Han population

Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which strongly promote proliferation of cancer cells in vitro and in vivo. Knowing that smoking is the most important risk factor for laryngeal carcinoma, we examined the relationships between CYP2C19*3 polymorphism, smoking and laryngeal carcinoma in the Chinese Han population. In a Chinese Han case-control study of 300 laryngeal carcinoma patients and 300 healthy controls, we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in laryngeal carcinoma patients (6.67 vs 2.67%; P = 0.02). Multiple logistic regression analysis showed smoking (odds ratio (OR) = 6.353, 95% confidence interval (CI) = 4.413-9.144; P < 0.001) and alcohol consumption (OR = 2.607, 95%CI = 1.130-6.016; P = 0.025) as independent risk factors for laryngeal carcinoma; there was a significant interaction between CYP2C19*3 and smoking (OR = 17.842, 95%CI = 13.32-31.102; P = 0.009). We conclude that CYP2C19*3 polymorphism is significantly associated with laryngeal carcinoma in the Chinese Han population.