Dataset Information

Association between polymorphisms in the CYP1A1, CYP2E1 and GSTM1 genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

ABSTRACT: Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 (CYP1A1) rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 (CYP2E1) rs2031920 C>T polymorphism increased EC risk, while the GSTM1 null genotype decreased EC risk. An association existed between the following: CYP1A1 rs4646903 and smoking in EC, GCC and GAC; CYP1A1 rs4646903 and alcohol consumption in EC and GCC; CYP2E1 rs2031920 and smoking in EC, GCC and GAC and CYP2E1 rs2031920 and alcohol consumption in EC and GCC. No association was observed between CYP1A1 and CYP2E1. The glutathione S-transferase mu 1 (GSTM1) null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The CYP1A1 rs4646903 and CYP2E1 rs2031920 polymorphisms were risk factors of GCC or EC, and the GSTM1 null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.

SUBMITTER: Zhao F

PROVIDER: S-EPMC6607096 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Association between polymorphisms in the <i>CYP1A1, CYP2E1 and GSTM1</i> genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Zhao Fang F Su Jing-Fen JF Lun Shu-Min SM Hou Yong-Jie YJ Duan Li-Juan LJ Wang Neng-Chao NC Shen Fang-Fang FF Zhang Yao-Wen YW Gao Zhao-Wei ZW Li Jing J Du Xian-Juan XJ Zhou Fu-You FY

Oncology letters 20190607 2

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confide ...[more]

PMID: 31423187

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Project description:AIM:To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer (SCRC) risk. METHODS:Six hundred forty-one individuals (227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1*2A, CYP1A1*2C CYP2E1*5B and CYP2E1*6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The EPHX1 Tyr113His, EPHX1 His139Arg and CYP1A1*2C polymorphisms were detected by real-time PCR. Chi-squared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05. RESULTS:Age over 62 years was a risk factor for SCRC development (OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC (OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant (heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant (OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant (OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models (OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant (heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic: OR = 7.32, 95%CI: 1.85-28.96, P < 0.01), dominant (OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive (OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant (OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models (OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B (C) and CYP2E1*6 (A) polymorphisms was associated with SCRC (P = 0.002). However, the CYP1A1*2A, CYP1A1*2C, EPHX1 Tyr113His and EPHX1 His139Arg polymorphisms were not associated with SCRC. CONCLUSION:In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.

Project description:BackgroundUpper tract urothelial carcinomas (UT-UC) can invade the pelvicalyceal system making differential diagnosis of the various histologically distinct renal cell carcinoma (RCC) subtypes and UT-UC, difficult. Correct diagnosis is critical for determining appropriate surgery and post-surgical treatments. We aimed to identify microRNA (miRNA) signatures that can accurately distinguish the most prevalent RCC subtypes and UT-UC form the normal kidney.Methods and findingsmiRNA profiling was performed on FFPE tissue sections from RCC and UT-UC and normal kidney and 434 miRNAs were significantly deregulated in cancerous vs. the normal tissue. Hierarchical clustering distinguished UT-UCs from RCCs and classified the various RCC subtypes among them. qRT-PCR validated the deregulated expression profile for the majority of the miRNAs and ROC analysis revealed their capability to discriminate between tumour and normal kidney. An independent cohort of freshly frozen RCC and UT-UC samples was used to validate the deregulated miRNAs with the best discriminatory ability (AUC>0.8, p<0.001). Many of them were located within cytogenetic regions that were previously reported to be significantly aberrated. miRNA targets were predicted using the miRWalk algorithm and ingenuity pathway analysis identified the canonical pathways and curated networks of the deregulated miRNAs. Using the miRWalk algorithm, we further identified the top anti-correlated mRNA/miRNA pairs, between the deregulated miRNAs from our study and the top co-deregulated mRNAs among 5 independent ccRCC GEO datasets. The AB8/13 undifferentiated podocyte cells were used for functional assays using luciferase reporter constructs and the developmental transcription factor TFCP2L1 was proved to be a true target of miR-489, which was the second most upregulated miRNA in ccRCC.ConclusionsWe identified novel miRNAs specific for each RCC subtype and UT-UC, we investigated their putative targets, the networks and pathways in which they participate and we functionally verified the true targets of the top deregulated miRNAs.

Dataset Information

Association between polymorphisms in the CYP1A1, CYP2E1 and GSTM1 genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Publications

Association between polymorphisms in the <i>CYP1A1, CYP2E1 and GSTM1</i> genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Similar Datasets

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