Association of CYP2C19 Polymorphisms with Survival of Breast Cancer Patients Using Tamoxifen: Results of a Metaanalysis

Background: Previous studies accessing the association of CYP2C19 with outcomes of patients using tamoxifenfor breast cancer have yielded conflicting results. The aim of this meta-analysis is to obtain a more precise estimateof effects of CYP2C19 polymorphisms and to clarify their effects on survival of the breast cancer patients usingtamoxifen. Materials and Methods: A systematic search of PubMed and Embase was performed, comparingpatients with or without CYP2C19*2 and CYP2C19*17, relevant articles searched for. The following outcomeswere included from the eligible studies: disease-free survival (DFS) and overall survival (OS), expressed byhazard ratios (HR) with corresponding 95% confidence interval (CI). Subgroup analysis by genotypes was alsoperformed. Pooled estimates were calculated using random-effect model in accordance to the heterogeneity.Results: Six studies met the inclusion criteria. The integrated OR on the association between CYP2C19 andDFS, calculated by the random-effect model, was 0.54 (95%CI=0.34-0.84, p=0.013). Subgroup analysis showedthat both CYP2C19*2 and CYP2C19*17 were associated with increased survival. The pooled results of twostudies for OS were OR=0.46 (95%CI=0.21-1.01, p=0.233). Conclusions: This meta-analysis suggests that theCYP2C19*2 and CYP2C19*17 genotypes are associated with increased survival in breast cancer patients usingtamoxifen.     

CYP17 (T- 34C), CYP19 (Trp39Arg), and FGFR2 (C-906T) Polymorphisms and the Risk of Breast Cancer in South Indian Women

Breast cancer is initiated by exposure to endogenous and exogenous estrogens. A case-control (n=250-500)study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP’s) in CYP17 (T-34C),CYP19 (Trp39Arg) and FGFR2(C-906T). Genotyping was done using the Taqman allelic discrimination assayfor CYP17 (T-34C) and FGFR2 (T-906C) and PCR-CTPP for CYP19 (Trp39Arg). There was a significantprotective association of the (TT/CC) genotype of the CYP17 gene against the risk of developing breast cancer(OR=0.68, 95% CI: 0.49-0.96), which was more significant in postmenopausal women (OR=0.56, 95% CI: 0.35-0.89) (p=0.015). CYP19 (Trp39Arg) is a rare polymorphism and all the cases were homozygous for the wild typeTrp allele (100%); this was also the case for 99.2% of the controls. We were unable to detect any variant form ofthe CYP19 gene in south Indian women. There was no significant association between the risk of breast cancerand FGFR2 (C-906T). These results suggest that the CYP17 TT/CC genotype is associated with decreased riskfor breast cancer, especially in post menopausal women.     

Breast Cancer Association with CYP1A2 Activity and Gene Polymorphisms - a Preliminary Case-control Study in Tunisia

The aim of the present study was to evaluate the relative contribution of CYP1A2 isoforms (-3860 G/A,-2467T/delT and -163C/A) in control subjects and breast cancer patients to the metabolism of caffeine in humanliver. Restriction fragment length polymorphism analysis of PCR-amplified Fragments (PCR-RFLP) was usedfor the genotyping of CYP1A2 SNPs and HPLC allowed the phenotyping through the measurement of CYP1A2activity using the 17X + 13X + 37X/137X urinary metabolite ratio (CMR) and plasma caffeine half life (T1/2).The CYP1A2 -3860A genotype was associated with a decreased risk of breast cancer. In contrast, distributionsof the CYP1A2 -2467T/delT or -2467delT/delT and -163A/C or A/A genotypes among breast cancer patients andcontrols were similar. When the genotype and phenotype relationship was measured by comparing the meanCMR ratios and caffeine half life within the genotype groups between subjects and breast cancer patients, therewere no significant differences except for -3860 A, most of them being homozygous for the -3860 G/G SNP andhad a significant higher mean CMR ratio and half life than those with -3860 G/A (P=0.02). The results of thispreliminary study show a significant association between CP1A2 -3860 G variant and CYP1A2 phenotype whichmust be confirmed by further large-size case-control studies.     

CYP2C19*17 is associated with decreased breast cancer risk

Cytochrome P450 2C19 (CYP2C19) plays an important role in the metabolism of xenobiotics and drugs and contributes to the catabolism of endogenous substrates like estradiol. Genetic variability impacts expression and activity of CYP2C19 and therefore can influence catabolism of estrogens. In the present study we analyzed the association of three polymorphisms of CYP2C19 namely CYP2C19*2 (CYP2C19_681_G>A, rs4244285), CYP2C19*3 (CYP2C19_636_G>A, rs57081121) and CYP2C19*17 (CYP2C19_-806_C>T, rs12248560), with breast cancer susceptibility. We genotyped 1,015 breast cancer cases and 1,021 age-matched, population-based controls of the German GENICA study by matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Risk estimates were calculated by logistic regression. All tests were two-sided. We observed a decreased breast cancer risk for carriers of the CYP2C19*17 allele (OR 0.77, 95% CI: 0.65–0.93; P = 0.005). In subgroup analysis we observed a significant decreased breast cancer risk for women using hormone therapy for ten years or longer who were carriers of the CYP2C19*17 allele (OR 0.57, 95% CI: 0.39–0.83; P = 0.003). Since CYP2C19*17 defines an ultra rapid metabolizer phenotype we suggest that an increased catabolism of estrogens by CYP2C19 may lead to decreased estrogen levels and therefore reduces breast cancer risk. This protective effect seems to be stronger in combination with long-term intake of supplemental estrogens during hormone therapy.     

Association of CYP1A1 rs1048943 Polymorphism with Prostate Cancer in Iraqi Men Patients

Objective: The purpose of this study was to evaluate the relationship between CYP1A1 gene rs1048943 polymorphism and the risk of Iraqi men with prostate cancer. Methods: In this research, we conducted a population-based approach that intersects high-throughput genotype information from  different population of Iraq to estimate the frequency of genotypes associated with prostate cancer responsivenessOur study included a total of 100 patients and 150 healthy controls. rs1048943 genotyping has been investigated in Iraqi men in connection with prostate cancer. Results: We observed that individuals with the rs1048943 GA genotype had an increased risk of prostate cancer relative to those with the AA genotype  ( OR 95% CI of 0.449 :95%CI 0.23-0.90; P = 0.002). We found in the dominant model that the rs1048943 GA and GG genotype displayed an increased risk of prostate cancer relative to the AA genotype   ( OR 95% CI of 0.680 :95%CI 0.4-1.17; P = 0.018). Conclusion: Polymorphism RS 1048943 in the CYP1A1 gene is associated with the risk of developing prostate cancer and is possibly one of the most significant factors in its development.     

Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women

Background: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study. Materials and Methods: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population. Conclusions: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.     

Effects of the CYP2C19 Genetic Polymorphism on Gastritis,Peptic Ulcer Disease,Peptic Ulcer Bleeding and Gastric Cancer

Background: The CYP2C19 genotype has been found to be an important factor for peptic ulcer healing andH. pylori eradication, influencing the efficacy of proton pump inhibitors (PPIs) and the pathogenesis of gastriccancer. The aim of this study was to investigate clinical correlations of the CYP2C19 genotype in patients withgastritis, peptic ulcer disease (PUD), peptic ulcer bleeding (PUB) and gastric cancer in Thailand. Materialsand Methods: Clinical information, endoscopic findings and H. pylori infection status of patients were assessedbetween May 2012 and November 2014 in Thammasat University Hospital, Thailand. Upper GI endoscopy wasperformed for all patients. Five milliliters of blood were collected for H. pylori serological diagnosis and CYP2C19study. CYP2C19 genotypes were determined by polymerase chain reaction (PCR) and restriction fragment lengthpolymorphism analysis (RFLP) and classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poormetabolizer (PM). Results: A total of 202 patients were enrolled including 114 with gastritis, 36 with PUD, 50 withPUB and 2 with gastric cancer. Prevalence of CYP2C19 genotype was 82/202 (40.6%) in RM, 99/202 (49%) inIM and 21/202 (10.4%) in PM. Overall H. pylori infection was 138/202 patients (68.3%). H. pylori infection wasdemonstrated in 72% in RM genotype, 69.7% in IM genotype and 47.6% in PM genotype. Both gastric cancerpatients had the IM genotype. In PUB patients, the prevalence of genotype RM (56%) was highest followed byIM (32%) and PM(12%). Furthermore, the prevalence of genotype RM in PUB was significantly greater thangastritis patients (56% vs 36%: p=0.016; OR=2.3, 95%CI=1.1-4.7). Conclusions: CYP2C19 genotype IM was themost common genotype whereas genotype RM was the most common in PUB patients. All gastric cancer patientshad genotype IM. The CYP2C19 genotype RM might be play role in development of PUD and PUB. Furtherstudy in different population is necessary to verify clinical usefulness of CYP2C19 genotyping in developmentof these upper GI diseases.     

Association between the CYP1A2 rs762551 Polymorphism and Bladder Cancer Susceptibility: a Meta-Analysis Based on Case-Control Studies

Background: Previous studies evaluated associations between the CYP1A2 rs762551 polymorphism andbladder cancer risk. However, the results were inconsistent. We therefore performed a meta-analysis of thepublished case-control studies to assess in detail the association between CYP1A2 rs762551 polymorphism andbladder cancer risk. Materials and Methods: PubMed, Embase and Web of Science were searched to identifyrelevant studies and the pooled odds ratio (OR) and 95 % confidence interval (95%CI) were calculated. Results:A total of seven articles including 3,013 cases and 2,771 controls were finally included. Overall, a significantassociation was found between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for CCvs AA (OR=0.82, 95% CI=0.69~0.99), but no significant associations were found for the other three models (ACvs AA: OR=0.91, 95% CI=0.81~1.02; the dominant model: OR=0.90, 95% CI=0.80~1.00; the recessive model:OR=0.84, 95% CI =0.72~1.00). In the subgroup analysis by ethnicity, we detected significant associationsbetween the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for GA vs GG (OR = 0.78,95% CI =0.64~0.96) and for the recessive model (OR=0.80, 95% CI=0.66~0.96) in Caucasians, but not forAsians. Conclusions: The results from the meta-analysis suggested that the CYP1A2 rs762551 polymorphism isa protective factor for bladder cancer, especially in Caucasians.     

CYP3A4 Expression in Breast Cancer and its Association with Risk Factors in Mexican Women

Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450(CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplasticdrugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. Inthis report, we analyzed the protein expression in patients with BCa and in healthy women. Links with someclinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyseswere conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar deEspecialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time periodfrom 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed usingχ2 or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means.Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison withhealthy tissue. A significant association between protein expression with smoking, alcoholism and hormonalcontraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor(PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa developmentand can be used in the prediction of tumor response to different treatments. One therapeutic approach may thusbe to block CYP3A4 function.     

Impact of CYP2D6 Polymorphisms on Tamoxifen Responses of Women with Breast Cancer: A Microarray-based Study in Thailand

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the associationbetween genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients.We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 geneticpolymorphisms using microarray-based technology. Associations between genotypes-phenotypes and diseasefree survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years.The 3 common allelic frequencies were 43.8% (*10), 36.5 (*1) and 10.4% (*2) which are related to extensivemetabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No associationbetween CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statisticallysignificant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95% CI, 1.48 –31.69; P = 0.005).Furthermore, we observed statistically significant shorter DFS of homozygous CYP2D6*10 when comparedwith heterozygous CYP2D6*10 and other genotypes (P=0.005). CYP2D6*10 was the most common genotype inour subjects. Post-menopause patients with homozygous CYP2D6*10 and IM have shorter DFS. To confirm thisrelationship, larger samples and comprehensively designed trials in Thailand are required.     

Correlation of CYP2B6, CYP2C19, ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients

CYP2B6, CYP2C19, ABCC4, and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan-Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.     

NAT2 and CYP1A2 Polymorphisms and Lung Cancer Risk in Relation to Smoking Status

We investigated the associations between lung cancer and the gene polymorphisms of the drug metabolizingenzymes, containing cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2), glutathione S-transferaseclass mu (GSTM1), and N-acetyltransferase 2 (NAT2). The study involved 113 lung cancer patients and 121 noncancercontrols divided into never, light and heavy smokers according to pack-years of smoking in Japanese byusing PCR-RFLP. For light smokers, the lung cancer risk of NAT2 intermediate-slow was significantly increased[the adjusted odds ratio (OR): 10.9, 95% confidence intervals (95%CI): 1.75-67.5, P-value: 0.010]. Moreover,never smokers having joint genotypes of NAT2 intermediate-slow and CYP1A2*1F A/A was also associated withincreased the lung cancer risk (OR: 4.95, 95% CI: 1.19-20.6, P-value: 0.028). We suggested that light smokerswith intermediate-slow NAT2 activity were at highest risk for lung cancer and the gene-gene interaction based onintermediate-slow NAT2 activity and high CYP1A2 activity would be increased a lung cancer risk among neversmokers.     

CYP1A1 Polymorphisms and Risk of Lung Cancer in the Ethnic Kashmiri Population

The CYP1A1 category of enzymes plays a central role in the metabolic activation of major tobaccocarcinogens. Several polymorphisms within the CYP1A1 locus have been identified and have been shownto be associated with lung cancer risk, particularly in Asian populations. Here we focused on the influenceof three polymorphisms on lung cancer in ethnic Kashmiris, genotyping 109 lung cancer cases and 163healthy controls by PCR-RFLP methods. While no polymorphic alleles in CYP1A1m4 (exon 7 thr toasn) site were detected in our population, the allele frequency of CYP1A1m1 (Msp1) and CYP1A1m2(exon 7 ile to val) were 30.1 and 26.6 in controls and 44.5 and 38.9 in cases. The CYP1A1m1 andCYP1A1m2 variants were significantly associated with lung cancer susceptibility (ORs; 2.65, CI 95% =1.562-4.49 and 2.24,CI 95%=1.35-3.73).This risk was prominent in case of SCC compared with AC orother types of lung cancer. Stratified analysis showed a multiplicative interaction between tobaccosmoking and variant CYP1A1m1 genotype on the risk of SCC. The ORs of SCC for non-smokers were2.08 and 3.15 for smokers. When stratified by pack years, effect was stronger in the heaviest smokers(ORs=6.00,95% CI=1.672-21.532).The interaction between tobacco smoking and variant CYP1A1m2genotype followed similar pattern. Our findings thus support the conclusion that CYP1A1m1 and m2polymorphisms are associated with the smoking related lung cancer risk in Kashmiri population.     

Lack of Association between CYP1A1 M2 and M4 Polymorphisms and Breast Carcinoma in Jordanian Women: a Case-Control Study

Background: CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. Purpose: The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. Materials and Methods: Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BIRADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. Results: No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p-value = 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p-value= 0.95; OR= 0.95; 95% CI= 0.51- 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D’=1). Conclusions: Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females.     

CYP2D6 and CYP2E1 Gene Polymorphisms and their Association with Cervical Cancer Susceptibility: A Hospital Based Case-Control Study from South-Western Maharashtra

Background: In last few years several studies all over the world discovered the genetic polymorphisms in different cytochrome P450 genes associated with risk of various cancers, but contradictory outcomes were evidenced in case of cervical cancer risk.  In this case-control study we aimed to see whether the polymorphism of CYP2D6 or CYP2E1 genes may or may not be associated with cervical cancer risk in women of rural Maharashtra. Methods: In this case-control study, the association of CYP2D6 and CYP2E1 gene polymorphism with cervical cancer risk was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted with 350 clinically confirmed cervical cancer patients and 350 healthy women in a population of South-Western Maharashtra. The Odds ratio (OR) with 95% confidence interval and p-value were evaluated, where p ≤0.005 was considered as statistically significant. Results: After the analysis of SNP (rs389209) of CYP2D6 and SNPs (rs2031920, rs6413432, rs6413420) of CYP2E1, we noticed that variant allele A of CYP2E1*6 showed significant increase in cervical cancer cases (OR=4.81; 95% CI: 1.57- 14.77; p=0.005). The genotypic distribution of heterozygote G/A genotype of CYP2D6*4 showed negative association with cervical cancer development when age of cancer occurrence (OR=0.41; 95% CI: 0.27- 0.61; p<0.0001) and tobacco history (OR=0.35; 95% CI: 0.20- 0.59; p=0.0001) was considered. Conclusion: The findings from this study supported that rs6413432 SNP of CYP2E1*6 increased cervical cancer risk in the studied rural women population.     

贵州汉族人群乳腺癌与FGFR2 rs1219648多态性相关性研究*

目的：探讨贵州汉族人群成纤维细胞生长因子受体2（fibroblast growth factor receptor 2,FGFR2）基因单核苷酸多态性与女性乳腺癌易感性之间的相关性。方法：运用聚合酶链反应- 序列特异性引物（PCR-SSP ）方法分析106 例女性乳腺癌患者和116 例正常对照女性FGFR2 基因内含子5 rs 1219648 多态性的分布情况。结果：乳腺癌组FGFR2 基因单核苷酸多态性位点rs 1219648 的基因型（TT,TC,CC）频率分别为50.00% 、25.47% 和24.53% ,对照组分别为29.31% 、48.28% 和22.41% ,乳腺癌组与对照组T 等位基因频率分别为62.74% 和53.45% ,C 等位基因频率分别为37.26% 和46.55% ,FGFR2 rs 1219648 基因型频率及等位基因频率在乳腺癌组与对照组中的分布差异均有统计学意义（P<0.05）。 结论：FGFR2 基因内含子5 的单核苷酸位点rs 1219648 多态性与乳腺癌可能具有相关性。携带FGFR2 rs 1219648 的TT等位基因型的人群可能更易患乳腺癌。     

CYP2C19 pharmacogenetics in advanced cancer: compromised function independent of genotype

CYP2C19 is a drug-metabolising enzyme involved in the metabolism of a number of chemotherapeutic agents including cyclophosphamide. Variants of the CYP2C19 gene result in a loss of function polymorphism, which affects approximately 3% of the Caucasian population. These individuals are poor metabolisers (PM) of a wide range of medications including omeprazole (OMP). In healthy subjects PM can be identified through homozygous variant genotype. However, a discordance between CYP2C19 genotype and phenotype has been reported previously in a small study of cancer patients. To investigate whether CYP2C19 activity was decreased in patients with advanced cancer, CYP2C19 genotype was determined in 33 advanced cancer patients using PCR-RFLP analysis for the two important allelic variants (*2,681G>A and *3,636G>A) and the activity of the enzyme was evaluated using the CYP2C19 probe drug OMP. The activity of the drug-metabolising enzyme CYP2C19 was severely compromised in advanced cancer patients, resulting in a PM status in 37% of the patients who had normal genotype. This is significantly (P<0.0005) higher than that would be predicted from the genotypic status of these patients. There was no evidence of a correlation between compromised CYP2C19 activity and any of the proinflammatory cytokines or acute phase response proteins studied. However, there was preliminary evidence of an association between PM status and low body mass (P=0.03). There is increasing interest in using pharmacogenetics to 'individualise medicine', however, the results of this study indicate that in a cancer population genotyping for CYP2C19 would significantly underestimate the number of phenotypic PM of drugs, such as cyclophosphamide, which may be metabolised by this enzyme.     

Association of CYP3A5*3 and CYP1A1*2C Polymorphism with Development of Acute Myeloid Leukemia in Egyptian Patients

Aim: Cytochrome P450 (CYP) enzyme catalyzes the phase I metabolism reaction which metabolize endogenous and exogenous DNA-reactive chemical compounds and xenobiotics which could induce genotoxicity and increase the risk for leukemia. We aimed to detect frequency of CYP3A5*3 and CYP1A1*2C polymorphisms in Egyptian acute myeloid leukemia (AML) patients and to determine role of allele’s variants as a risk factor for developing leukemia. Patients and Methods: A case-control study was conducted on seventy acute myeloid leukemia patients and thirty control subjects. Samples were analyzed for prevalence of CYP3A5*3 and CYP1A1*2C polymorphisms using PCR - restriction fragment length polymorphism method. Results: CYP3A5*3 polymorphism (3/3) and (1/3) genotype were significantly elevated in AML group compared to control group (p=0.002). However, no statistical significant differences were found between patients and control group as regard CYP1A1*2C polymorphism. Conclusion: Our results suggest that Egyptians carrying CYP3A5*3 polymorphism might have an increased risk of AML emphasizing the significance of effective phase I detoxification in carcinogenesis.     

CYP2C19 Genotype,CagA Genotype and Antibiotic Resistant Strain of Helicobacter pylori Infection

Background: H. pylori is a class I carcinogen and major cause of gastric cancer. Few previous studies reportedrelationship between H. pylori infection, CYP2C19 genotype and functional dyspepsia (FD) subtype. The aim of thisstudy was to determine relationship between CYP2C19 genotype and FD subtype patients(host factor) with antibioticresistant strains of H. pylori infection and CagA genotype(bacterial factor). Methods: FD patients who were investigatedwith gastroscopy at Thammasat University Hospital, Thailand during March 2017-November 2017 were enrolled. Twoantral gastric biopsies were obtained for rapid urease test, E-test and cultures. CagA genotypes (CagA1a and CagA2a)were determined by PCR and CYP2C19 genotype was determined by PCR-RFLP. FD patients were categorized asepigastric pain syndrome(EPS) and postprandial distress syndrome (PDS). Results: 93 FD patients with H. pyloriinfection were enrolled (37 male, 56 female, mean age 54.5 years). There were 33 patients with EPS and 60 patientswith PDS. CYP2C19 genotype revealed 55.9% rapid metabolizer (RM), 40.9% intermediate metabolizer (IM) and3.2% poor metabolizer (PM) genotypes. Antibiotics susceptibility tests demonstrated 62.8% resistant to metronidazole,12.9% resistant to clarithromycin and 27.1% resistant to fluoroquinolone. CagA 1a and CagA 2a were demonstratedin 6 patients(11.5%) and 46 patients(88.5%). CagA2a genotype was more prevalent in PDS than EPS patients(94.3%vs.76.5%; P =0.08) without significance. In intermediate metabolizer (IM), CagA2a genotype was significanthigher in PDS than EPS(100% vs.25%; P=0.004). Conclusions: PDS, CYP2C19 RM genotype and CagA 2a gene ofH. pylori infection were the predominant type of FD in Thailand. Metronidazole remain the most common antibioticresistant strain of H. pylori infection in FD patients. PDS (host factor) was significantly related to CagA2a genotype(bacterial factors) only in patients with intermediate metabolizer. Appropriate dose of proton pump inhibitor (PPI) andcorrect regimens for H. pylori eradication in FD patients should be consider to improve clinical outcomes.     

Four Polymorphisms in the Cytochrome P450 1A2 (CYP1A2) Gene and Lung Cancer Risk: a Meta-analysis

Background: Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526,and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present metaanalysisof the literature was performed to derive a more precise estimation of the relationship. Materials andMethods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls forCYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysisfor the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominantmodel (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lungcancer was observed in Caucasians (dominant model: OR=1.29, 95%CI=1.11-1.51; recessive model: OR=1.33,95%CI=1.01-1.75; additive model: OR=1.49, 95%CI=1.12-1.98). There was no evidence of significant associationbetween lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: Insummary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lungcancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514associations in lung cancer, where at least some of the covariates responsible for heterogeneity could be controlled,to obtain a more conclusive understanding about the function of the rs2069514 polymorphism in lung cancerdevelopment.