• Breast carcinoma
• CYP1A2*rs762551
• Cytochrome P450
• Genetic variants

• Female
• Humans
• Breast Neoplasms/genetics
• Case-Control Studies
• Cytochrome P-450 CYP1A2/genetics
• Genetic Predisposition to Disease
• Polymorphism, Single Nucleotide

• Curcumin
• Gastric cancer
• Molecular docking
• Network pharmacology
• Survival analysis

• Humans
• Cytochrome P-450 CYP1A1/genetics
• Polymorphism, Single Nucleotide
• Cytochrome P-450 CYP2C8/genetics
• Cytochrome P-450 CYP2C9/genetics
• Case-Control Studies
• Cytochrome P-450 CYP2B6/genetics
• India/epidemiology
• Genotype
• Gastrointestinal Neoplasms/genetics
• Cytochrome P-450 CYP1B1/genetics

• Digestive cancer
• Gastrointestinal cancer
• Microbial dysbiosis
• Oral microbiota Systematic review.

• Humans
• Biomarkers
• Microbiota
• Mouth
• Neoplasms

• Humans
• Female
• Uterine Cervical Neoplasms/epidemiology
• Uterine Cervical Neoplasms/genetics
• Rural Population
• Cytochrome P-450 CYP2C19/genetics
• Cytochrome P-450 CYP2C8
• Case-Control Studies
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP2C9
• India/epidemiology
• Polymorphism, Single Nucleotide
• Cytochrome P-450 Enzyme System

• Gastric cancer
• Helicobacter pylori
• Infection
• Meta-analysis
• Prevalence
• Systematic review

• Humans
• Stomach Neoplasms/epidemiology
• Helicobacter pylori
• Prevalence
• Retrospective Studies
• Africa

• CYP1A1
• CYP1A2
• Disease risk
• Drug response
• Metabolism
• SNPs

Background and aim

As a distinguished system, the cytochrome P450 (CYP) enzyme superfamily is involved in the biotransformation of several endogenous and exogenous substances including drugs, toxins, and carcinogens. Reports on the role of CYP enzyme in gastric cancer (GC) from the Eastern region of India are scarce. The present study aimed to evaluate the effect of single nucleotide polymorphisms (SNP) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9*3) among cases with gastric malignancy.

Material and methods

The current study is a cross-sectional observational study carried out among 113 GC cases attending the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, and Srirama Chandra Bhanja Medical College and Hospital, Cuttack, India. Two ml of venous blood was collected from the confirmed cases of GC. The samples were subjected to genomic DNA isolation followed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP).

Results

The prevalence of both homozygous and heterozygous mutation in GC cases is 4% and 8%, respectively. The overall association of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) mutation in GC cases is 12% whereas 88% were detected as wild/standard type. The mutation CYP2C9 SNP has been seen in Helicobacter pylori-infected cases and as well as those without H. pylori infection.

Conclusions

The CYP2C9*3 genetic polymorphism might play a significant role as a risk factor for the development of gastric malignancy irrespective of H. pylori infection, among the eastern Indian population.

• gastric cancer
• genome-scale metabolic model
• metabolism
• transcriptome

Background: Dysregulation of lipid metabolism plays important roles in the tumorigenesis and progression of gastric cancer (GC). The present study aimed to establish a prognostic model based on the lipid metabolism–related genes in GC patients.

Materials and Methods: Two GC datasets from the Gene Expression Atlas, GSE62254 (n = 300) and GSE26942 (n = 217), were used as training and validation cohorts to establish a risk predictive scoring model. The efficacy of this model was assessed by ROC analysis. The association of the risk predictive scores with patient characteristics and immune cell subtypes was evaluated. A nomogram was constructed based on the risk predictive score model and other prognostic factors.

Results: A risk predictive score model was established based on the expression of 19 lipid metabolism–related genes (LPL, IPMK, PLCB3, CDIPT, PIK3CA, DPM2, PIGZ, GPD2, GPX3, LTC4S, CYP1A2, GALC, SGMS1, SMPD2, SMPD3, FUT6, ST3GAL1, B4GALNT1, and ACADS). The time-dependent ROC analysis revealed that the risk predictive score model was stable and robust. Patients with high risk scores had significantly unfavorable overall survival compared with those with low risk scores in both the training and validation cohorts. A higher risk score was associated with more aggressive features, including a higher tumor grade, a more advanced TNM stage, and diffuse type of Lauren classification of GC. Moreover, distinct immune cell subtypes and signaling pathways were found between the high–risk and low–risk score groups. A nomogram containing patients’ age, tumor stage, adjuvant chemotherapy, and the risk predictive score could accurately predict the survival probability of patients at 1, 3, and 5 years.

Conclusion: A novel 19-gene risk predictive score model was developed based on the lipid metabolism–related genes, which could be a potential prognostic indicator and therapeutic target of GC.

• gastric cancer
• gene expression omnibus dataset
• gene panel
• lipid metabolism
• nomogram
• prognostic model

• Gastric adenocarcinoma
• gene expression
• hub genes
• prognostic values
• survival analysis

• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Computational Biology
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology

• National Natural Science Foundation of China

Functional dyspepsia (FD) is a common chronic gastrointestinal disorder with a complex, undefined mechanism. Clustering of patients with FD in families highlights the role of genetic factors in the pathogenesis of FD. We performed a systematic review and meta-analysis to clarify the associations between specific gene polymorphisms and FD susceptibility. PubMed, EMBASE, the Cochrane Library, and HuGE database were searched. An additive model was adopted to determine whether previous studied genes are associated with FD susceptibility. Carriers of minor allele in GNB3 825C>T (OR = 1.15, 95% CI 0.99-1.34, P = 0.07), SCL6A4 5HTTLPR (OR = 0.92, 95% CI 0.75-1.12, P = 0.40), and CCK-1R 779T>C (OR = 0.86, 95% CI 0.72-1.03, P = 0.09) genes failed to demonstrate susceptibility to FD. In a subgroup analysis, only minor allele (T) in GNB3 825C>T was associated with an increased susceptibility to the epigastric pain syndrome subtype (OR = 1.34, 95% CI 1.10-1.63, P = 0.003). Our meta-analysis based on available studies using an additive model failed to show that GNB3, SCL6A4, and CCK-1R polymorphisms are associated with FD susceptibility.

Cytochrome P450 1A2 (CYP1A2) is one of the major CYP450 enzymes (CYPs) in the liver, and participates in the biotransformation of various xenobiotics and endogenous signaling molecules. The expression and activity of CYP1A2 show large individual differences, due to genetic and environmental factors. In order to discover non-invasive serum biomarkers associated with hepatic CYP1A2, mass spectrometry-based, untargeted metabolomics were first conducted, in order to dissect the metabolic differences in the serum and liver between control rats and β-naphthoflavone (an inducer of CYP1A2)-treated rats. Real-time reverse transcription polymerase chain reaction and pharmacokinetic analysis of phenacetin and paracetamol were performed, in order to determine the changes of mRNA levels and activity of CYP1A2 in these two groups, respectively. Branched-chain amino acids phenylalanine and tyrosine were ultimately focalized, as they were detected in both the serum and liver with the same trends. These findings were further confirmed by absolute quantification via a liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based targeted metabolomics approach. Furthermore, the ratio of phenylalanine to tyrosine concentration was also found to be highly correlated with CYP1A2 activity and gene expression. This study demonstrates that metabolomics can be a potentially useful tool for biomarker discovery associated with CYPs. Our findings contribute to explaining interindividual variations in CYP1A2-mediated drug metabolism.

• CYP1A2
• branched-chain amino acids
• endogenous biomarkers
• metabolomics
• phenylalanine
• tyrosine

• Biomarkers
• Case-control
• Gastric cancer
• Microbiota
• Tongue coating

Objective: Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions in gastric cancer (GC). Previous studies demonstrated genetic variants within mTORC1 genes were associated with GC risk. However, no studies reported the associations between genetic variants within mTORC1 genes and GC prognosis. Herein, we firstly assessed the associations of genetic variants of mTORC1 genes with overall survival (OS) of GC in Chinese populations.

Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in mTORC1 genes (i.e., rs2536 T>C and rs1883965 G>A for mTOR, rs3160 T>C and rs26865 A>G for MLST8, rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A for RPTOR) by the TaqMan method in 197 Chinese GC patients who had surgical resection in Xinhua Hospital. We conducted Kaplan-Meier survival plots and Cox hazards regression analysis to explore the associations of these SNPs with OS.

Results: The single-locus analysis indicated that RPTOR rs1062935 T>C was associated with an increased risk of poor GC prognosis (CC vs. TT/TC: adjusted Hazard ratio (HR) = 1.71, 95% confidence interval (CI) = 1.04-2.82). The combined analysis of all eight SNPs showed that patients with more than three risk genotypes significantly increased risk of death (adjusted HR = 2.44, 95% CI = 1.30-4.58), when compared to those with three or less risk genotypes.

Conclusions: Our findings indicated that genetic variants within mTORC1 genes may predict GC prognosis in Chinese populations. The results need to be validated in future studies with larger sample sizes.

• clinical outcome
• gastric cancer
• genetic variants
• mTORC1

To evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC).

In this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 ancestry-informative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4, R environment and SPSS v.20.

After statistical analyses with the control of confounding factors, such as genetic ancestry, three markers (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers (rs28362491) and the marker in the UGT1A1 gene (rs8175347) were positively associated with the development of CRC. Therefore, we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly, carriers of the combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.

These findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.

• Inflammatory processes
• Immune response
• Genomic and cellular stability
• Gastric cancer
• Colorectal cancer
• Amazon

• Alleles
• Biomarkers, Tumor/genetics
• Brazil/epidemiology
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/genetics
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Incidence
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/genetics

Helicobacter pylori (H. pylori) is closely related with some diseases such as chronic gastritis, peptic ulcer, gastric mucosa associated lymphoid tissue lymphoma, and gastric cancer. The pathogenicity of H. pylori mainly relies on its flagellum, spiral structure, lipopolysaccharide, cytotoxin associated protein A, and vacuolating cytotoxin A. Through complex pathogenic mechanisms, H. pylori causes various kinds of diseases. In this paper, we discuss the latest research progress in the understanding of the virulence factors and pathogenic mechanism of H. pylori.

• Helicobacter pylori
• Virulence factors
• Pathogenic mechanism

• Breast cancer
• CYP1A1
• GSTP1
• Mutations
• SSCP
• Xenobiotic metabolizing pathway

• Dyspepsia
• Gastritis
• Helicobacter pylori
• Intestinal metaplasia
• Pepsinogen II polymorphism

Cytochrome P450 1A1 (CYP1A1) is a phase I enzyme that regulates the metabolism of environmental carcinogens and alter the susceptibility to various cancers. Many studies have investigated the association between the CYP1A1 MspI and Ile462Val polymorphisms and digestive tract cancer (DTC) risk in different groups of populations, but their results were inconsistent. The PubMed and Embase Database were searched for case–control studies published up to 30th September, 2015. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the relationship. Totally, 39 case–control studies (9094 cases and 12,487 controls) were included. The G allele in Ile/Val polymorphism was significantly associated with elevated DTC risk with per‐allele OR of 1.24 (95% CI = 1.09–1.41, P = 0.001). Similar results were also detected under the other genetic models. Evidence was only found to support an association between MspI polymorphism and DTC in the subgroups of caucasian and mixed individuals, but not in the whole population (the dominant model: OR = 1.19, 95% CI = 0.94–1.91, P = 0.146). In conclusion, our results suggest that the CYP1A1 polymorphisms are potential risk factors for DTC. And large sample size and well‐designed studies with detailed clinical information are needed to more precisely evaluate our founding.

• CYP1A1
• digestive tract cancer
• meta-analysis
• polymorphism

• DraI
• RsaI/PstI
• cytochrome P450 2E1
• gastric cancer
• meta-analysis
• polymorphism

• Cytochrome P-450 CYP1A2/genetics
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• Polymorphism, Single Nucleotide
• Risk Factors
• White People

• Gastric cancer
• Gene ontology
• Prognostic gene for clinical detection

• Anticancer therapy
• CYP450 inhibitors
• Drug metabolism
• Genetic predisposition
• Pharmacogenetics

• Cytochrome P-450 Enzyme Inhibitors/pharmacology
• Cytochrome P-450 Enzyme System/chemistry
• Cytochrome P-450 Enzyme System/genetics
• Cytochrome P-450 Enzyme System/physiology
• Genetic Predisposition to Disease
• Humans
• Inactivation, Metabolic
• Neoplasms/genetics
• Neoplasms/therapy
• Pharmacogenetics
• Polymorphism, Genetic
• Treatment Outcome

This study was conducted to explore the effects of genetic polymorphisms (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C) and environmental factors (smoking and drinking) on susceptibility to laryngeal cancer in a Han Chinese study group.

This case-control study included 552 Han Chinese patients diagnosed with laryngeal cancer and 666 healthy control subjects of the same ethnicity, similar age, and gender. Genetic polymorphisms were examined using multi-PCR and Matrix Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF MS) methodology. The association of these genetic and environmental factors with susceptibility to laryngeal cancer was evaluated using a statistical approach.

The frequencies of all three polymorphisms in the patient cohort were significantly different from those in the control cohort. Compared to the control cohort, carriers of variant alleles of CYP1B1*2 355T and CYP2E1*5 -1293C showed a higher risk for developing laryngeal cancer (for CYP1B1*2 355T, adjusted OR = 2.657, P <0.001; for CYP2E1*5 -1293C, adjusted OR = 1.938, P <0.001), while carriers of mutation allele CYP1B1*3 4326G showed a lower risk (adjusted OR = 0.562, P <0.001). Joint effects of these polymorphisms were observed. When compared to haplotype G₃₅₅C₄₃₂₆G₋₁₂₉₃, haplotypes T₃₅₅C₄₃₂₆G₋₁₂₉₃ (adjusted OR = 1.809, P <0.001), G₃₅₅C₄₃₂₆C₋₁₂₉₃ (adjusted OR = 1.644, P = 0.044), and T₃₅₅C₄₃₂₆C₋₁₂₉₃ (adjusted OR = 3.104, P <0.001) were associated with a significantly higher laryngeal cancer risk. The adjusted ORs for non-smokers, non-drinkers, smokers, and drinkers with the GT/TT genotype at CYP1B1*2 G355T were 2.190 (P = 0.006), 2.008 (P = 0.001), 5.875 (P <0.001), and 4.518 (P <0.001), respectively.

CYP1B1*2 355T and CYP2E1*5 -1293C are associated with an increased laryngeal cancer risk, while CYP1B1*3 4326G is associated with a decreased risk. These polymorphisms showed joint effects on laryngeal cancer risk. Smoking and drinking showed collaborative effects with two high risk alleles (CYP1B1*2 355T and CYP1B1*3 4326G) for promoting laryngeal cancer risk.

• Alcohol Drinking/adverse effects
• Alcohol Drinking/genetics
• Alleles
• Asian People/genetics
• Case-Control Studies
• Cytochrome P-450 CYP1B1/genetics
• Cytochrome P-450 CYP2E1/genetics
• Female
• Genetic Predisposition to Disease/genetics
• Haplotypes/genetics
• Humans
• Laryngeal Neoplasms/etiology
• Laryngeal Neoplasms/genetics
• Male
• Middle Aged
• Polymorphism, Single Nucleotide/genetics
• Risk
• Risk Factors
• Smoking/adverse effects
• Smoking/genetics

• Carcinogen
• Gastric cancer
• Gastric diseases
• Helicobacter pylori
• p53 mutation

• Diet
• Genetic Variation
• Geography
• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter pylori/genetics
• Humans
• India/epidemiology
• Peptic Ulcer/microbiology
• Prevalence
• Smoking
• Social Class
• Species Specificity
• Stomach Neoplasms/complications
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/microbiology