|
1
|
DeBenedictis JN, Baars E, Ochoteco-Asensio J, van Breda SG, de Kok TM. Genetic Variability Impacts Genotoxic and Transcriptome Responses in the Human Colon after the Consumption of Processed Red Meat Products and Those with Added Phytochemical Extracts. Nutrients 2024; 16:425. [PMID: 38337709 PMCID: PMC10857093 DOI: 10.3390/nu16030425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/22/2024] [Accepted: 01/26/2024] [Indexed: 02/12/2024] Open
Abstract
The PHYTOME study investigated the effect of consuming processed meat products on outcomes related to colorectal cancer risk without testing the impact of genetic variability on these responses. This research aims to elucidate the genetic impact on apparent total N-nitroso compound (ATNC) excretion, colonic DNA adduct formation, ex vivo-induced DNA damage, and gene expression changes in colon biopsies of healthy participants. Through a systematic literature review, candidate polymorphisms were selected and then detected using TaqMan and PCR analysis. The effect of genotype on study outcomes was determined via a linear mixed model and analysis of variance. Machine learning was used to evaluate relative allele importance concerning genotoxic responses, which established a ranking of the most protective alleles and a combination of genotypes (gene scores). Participants were grouped by GSTM1 genotype and differentially expressed genes (DEGs), and overrepresented biological pathways were compared between groups. Stratifying participants by ten relevant genes revealed significant variations in outcome responses. After consumption of processed red meat, variations in NQO1 and COMT impacted responses in ATNC levels (µmol/L) (+9.56 for wildtype vs. heterozygous) and DNA adduct levels (pg/µg DNA) (+1.26 for variant vs. wildtype and +0.43 for variant vs. heterozygous), respectively. After phytochemicals were added to the meat, GSTM1 variation impacted changes in DNA adduct levels (-6.12 for deletion vs. wildtype). The gene scores correlated with these responses and DEGs were identified by GSTM1 genotype. The altered pathways specific to the GSTM1 wildtype group included 'metabolism', 'cell cycle', 'vitamin D receptor', and 'metabolism of water-soluble vitamins and co-factors'. Genotype impacted both the potential genotoxicity of processed red meat and the efficacy of protective phytochemical extracts.
Collapse
Affiliation(s)
| | | | | | - Simone G. van Breda
- Toxicogenomics Department, GROW School of Oncology & Reproduction, Faculty of Health, Medicine & Life Sciences, Maastricht University, 6211 LK Maastricht, The Netherlands (J.O.-A.)
| | | |
Collapse
|
|
2
|
Pu Y, Liu Q, Hu K, Liu X, Bai H, Wu Y, Zhou M, Fan P. CYP2E1 C-1054T and 96-bp I/D genetic variations and risk of gestational diabetes mellitus in chinese women: a case-control study. BMC Pregnancy Childbirth 2023; 23:403. [PMID: 37264354 DOI: 10.1186/s12884-023-05742-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 05/27/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND Cytochrome P450 2E1 (CYP2E1) plays a key role in the metabolism of xenobiotic and endogenous low-molecular-weight compounds. This study aimed to determine if the genetic variations of 96-bp insertion/deletion (I/D) and C-1054T (rs2031920) in CYP2E1 were associated with the risk of gestational diabetes mellitus (GDM). METHODS CYP2E1 polymorphisms were genotyped in a case-control study of 1,134 women with uncomplicated pregnancies and 723 women with GDM. The effects of genotype on the clinical, metabolic, and oxidative stress indices were assessed. RESULTS The CYP2E1 C-1054T variant was associated with an increased risk of GDM based on the genotype, recessive, dominant, and allele genetic models (P < 0.05). The TT + CT genotype remained a significant predictive factor for GDM risk after correcting for maternal age and pre-pregnancy body mass index (OR = 1.277, 95% CI: 1.042-1.563, P = 0.018). Moreover, fasting insulin concentrations and homeostatic model assessment of insulin resistance were significantly higher in GDM patients carrying the T allele than in those with the CC genotype (P < 0.05). Furthermore, the combined genotype II + ID/TT + CT of the 96-bp I/D and C-1054T polymorphisms further increased the risk of GDM when the combined genotype DD/CC was set as the reference category (OR = 1.676, 95% CI: 1.182-2.376, P = 0.004). CONCLUSIONS The T allele of the C-1054T polymorphism and its combination with the I allele of the 96-bp I/D variation in CYP2E1 are associated with an increased risk of GDM in the Chinese population. The - 1054T allele may be associated with more serious insulin resistance in patients.
Collapse
Affiliation(s)
- Yifu Pu
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Qingqing Liu
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Kaifeng Hu
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Xinghui Liu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Huai Bai
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Yujie Wu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Mi Zhou
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
| | - Ping Fan
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.
| |
Collapse
|
|
3
|
Pu Y, Liu Q, Liu H, Bai H, Huang W, Xi M, Fan P. Association between CYP2E1 C-1054T and 96-bp I/D genetic variations and the risk of polycystic ovary syndrome in Chinese women. J Endocrinol Invest 2023; 46:67-78. [PMID: 35943720 DOI: 10.1007/s40618-022-01885-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/27/2022] [Indexed: 01/12/2023]
Abstract
PURPOSE To investigate the association of cytochrome P450 2E1 (CYP2E1) C-1054T (rs2031920) and 96-bp I/D genetic variations with the risk of polycystic ovary syndrome (PCOS), and to estimate the effects of genotypes on the clinical, metabolic, hormonal, and oxidative stress indicators. METHODS This case-control study included 762 control women and 1034 patients with PCOS. Genotypes were determined using polymerase chain reaction and/or restriction fragment length polymorphism analysis. Clinical and biochemical parameters were also analyzed. RESULTS Frequencies of the TT + CT genotype (35.4 vs. 28.9%) and T allele (19.6 vs. 16.0%) of the CYP2E1 C-1054T polymorphism were significantly higher in the PCOS group than in the control group (OR = 1.350, 95% CI 1.103-1.652, P = 0.004 for the dominant model). Genotype TT + CT remained a significant predictor of PCOS in a logistic regression model including age, body mass index (BMI), and recruitment year of participants (OR = 1.345, 95% CI 1.071-1.688, P = 0.011). No statistical differences were found in the genotype and allele frequencies of CYP2E1 96-bp I/D polymorphism. However, the combined genotype DD/TT + CT was related to an increased risk of PCOS when the DD/CC wild-type combined genotype was used as a reference. Patients with the I allele of 96-bp I/D polymorphism had a lower BMI but higher plasma apolipoprotein B and oxidized low-density lipoprotein cholesterol levels than those with the DD genotype. CONCLUSION CYP2E1 C-1054T, but not 96-bp I/D, genetic polymorphism is associated with an increased risk of PCOS in Chinese women.
Collapse
Affiliation(s)
- Y Pu
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Q Liu
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - H Liu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - H Bai
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - W Huang
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - M Xi
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - P Fan
- Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
| |
Collapse
|
|
4
|
Sharzehan MAK, Sito H, Abdullah N, Alexiou A, Papadakis M, Jamal R, Tan SC. Association between CYP2E1 polymorphisms and colorectal cancer risk: a systematic review and meta-analysis. Sci Rep 2022; 12:20149. [PMID: 36418904 PMCID: PMC9684517 DOI: 10.1038/s41598-022-24398-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 11/15/2022] [Indexed: 11/24/2022] Open
Abstract
CYP2E1 encodes an enzyme that participates in the activation of several carcinogenic substances. Thus, numerous studies have investigated the association between CYP2E1 polymorphisms and colorectal cancer (CRC) risk, but inconclusive results have been obtained. We performed a meta-analysis to precisely evaluate the relationship of CYP2E1 rs2031920, rs3813867, and rs6413432 polymorphisms with the susceptibility to CRC. Scopus, Web of Science and PubMed databases were searched to identify eligible studies, and the association between the polymorphisms and CRC risk was then quantitatively synthesized using different genetic models. Eighteen studies with 23,598 subjects were selected for inclusion into the analysis. Significant association between rs2031920 and an increased CRC risk was observed in homozygous (OR = 1.496, 95% CI 1.177-1.901, P = 0.001), recessive (OR = 1.467, 95% CI 1.160-1.857, P = 0.001) and allele (OR = 1.162, 95% CI 1.001-1.349, P = 0.048) models. Significant association was not found for rs3813867 and rs6413432 (P > 0.05). In conclusion, our results suggest that rs2031920, but not rs3813867 and rs6413432, is associated with the risk of CRC.
Collapse
Affiliation(s)
| | - Hilary Sito
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Noraidatulakma Abdullah
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, Australia
- AFNP Med Austria, Wien, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.
| | - Rahman Jamal
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.
| |
Collapse
|
|
5
|
The Search for Cancer Biomarkers: Assessing the Distribution of INDEL Markers in Different Genetic Ancestries. Curr Issues Mol Biol 2022; 44:2275-2286. [PMID: 35678683 PMCID: PMC9164054 DOI: 10.3390/cimb44050154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 11/17/2022] Open
Abstract
Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of the population in this country, composed mainly by European (EUR), Native American (NAM), African (AFR), and Asian (ASN) ancestries. Among different populations, genetic markers commonly present diverse allelic frequencies, but in admixed populations, such as the Brazilian population, data is still limited, which is an issue that might influence cancer incidence. Therefore, we analyzed the allelic and genotypic distribution of 12 INDEL polymorphisms of interest in populations from the five Brazilian geographic regions and in populations representing EUR, NAM, AFR, and ASN, as well as tissue expression in silico. Genotypes were obtained by multiplex PCR and the statistical analyses were done using R, while data of tissue expression for each marker was extracted from GTEx portal. We highlight that all analyzed markers presented statistical differences in at least one of the population comparisons, and that we found 39 tissues to be differentially expressed depending on the genotype. Here, we point out the differences in genotype distribution and gene expression of potential biomarkers for risk of cancer development and we reinforce the importance of this type of study in populations with different genetic backgrounds.
Collapse
|
|
6
|
Effects of gene polymorphisms of metabolic enzymes on the association between red and processed meat consumption and the development of colon cancer; a literature review. J Nutr Sci 2018; 7:e26. [PMID: 30305892 PMCID: PMC6176493 DOI: 10.1017/jns.2018.17] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 06/08/2018] [Accepted: 08/17/2018] [Indexed: 12/15/2022] Open
Abstract
The role of environmental factors and genetic susceptibility in the development of colon cancer (CC) has been already proven, but the role of gene polymorphisms in modifying the risk of environmental factors such as nutritional factors is still unknown. This study aimed to investigate the effect of polymorphisms of involved genes in the association between red meat consumption and the development of CC. The present review was carried out using keywords such as polymorphism and/or protein and/or red meat and/or processed meat and/or colon cancer. PubMed and Science Direct databases were used to collect all related articles published from 2001 to 2017. The presence of SNP in the coding genes of proteins involved in metabolism of nutrients could play significant roles in the extent of the effects of nutrition in the development of CC. The effect of dietary proteins greatly depends on the polymorphisms in the metabolising genes of these substances. Gene polymorphisms may have a role in colorectal cancer risk, especially in people with high meat intake, and this leads to a difference in the effects of meat consumption in different individuals. To conclude, dietary recommendations for the prevention and control of CC should be modified based on the genotype of different individuals. Increasing our knowledge on this field of nutritional genomics can lead to personalised preventive and therapeutic recommendations for CC patients.
Collapse
|
|
7
|
Angel J, DiGiovanni J. Genetic Determinants of Cancer Susceptibility. COMPREHENSIVE TOXICOLOGY 2018:330-360. [DOI: 10.1016/b978-0-12-801238-3.65251-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
8
|
Cavalcante GC, Amador MAT, Ribeiro dos Santos AM, Carvalho DC, Andrade RB, Pereira EEB, Fernandes MR, Costa DF, Santos NPC, Assumpção PP, Ribeiro dos Santos Â, Santos S. Analysis of 12 variants in the development of gastric and colorectal cancers. World J Gastroenterol 2017; 23:8533-8543. [PMID: 29358861 PMCID: PMC5752713 DOI: 10.3748/wjg.v23.i48.8533] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 10/25/2017] [Accepted: 11/07/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC).
METHODS 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.
RESULTS 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.
CONCLUSION These findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.
Collapse
Affiliation(s)
- Giovanna C Cavalcante
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Marcos AT Amador
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
| | | | - Darlen C Carvalho
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Roberta B Andrade
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Esdras EB Pereira
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Marianne R Fernandes
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Danielle F Costa
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Ney PC Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Paulo P Assumpção
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Ândrea Ribeiro dos Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Sidney Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| |
Collapse
|
|
9
|
Fernandes GMM, Russo A, Proença MA, Gazola NF, Rodrigues GH, Biselli-Chicote PM, Silva AE, Netinho JG, Pavarino &EC, Goloni-Bertollo EM. CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms. World J Gastroenterol 2016; 22:9974-9983. [PMID: 28018104 PMCID: PMC5143764 DOI: 10.3748/wjg.v22.i45.9974] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 10/08/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
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.
Collapse
|
|
10
|
Peng H, Xie SK, Huang MJ, Ren DL. Associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk: a systemic review and meta-analysis. Tumour Biol 2013; 34:2389-95. [PMID: 23595220 DOI: 10.1007/s13277-013-0788-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2013] [Accepted: 04/01/2013] [Indexed: 02/07/2023] Open
Abstract
Cytochrome P450 2E1 (CYP2E1) is a natural enzyme involved in the metabolic activation of many carcinogens, and the functional polymorphisms in the CYP2E1 gene might have impacts on colorectal cancer risk. Many studies were published to assess the associations of CYP2E1 rs2031920 and rs3813867 polymorphisms with colorectal cancer risk, but no consistent findings were reported. A systemic review and meta-analysis of eligible studies was performed to comprehensively assess the associations above. Odds ratios (ORs) with 95 % confidence interval (95 % CIs) were used to assess the strength of the associations. Seventeen studies from 15 publications with 17,082 individuals were finally included into this meta-analysis. Meta-analysis of the 13 studies on CYP2E1 rs2031920 polymorphism showed that there was a significant association between CYP2E1 rs2031920 polymorphism and colorectal cancer risk under two genetic models (c2 versus c1: OR = 1.19, 95 % CI 1.03-1.37, P = 0.022; c2c2/c2c1 versus c1c1: OR = 1.16, 95 % CI 1.00-1.35, P = 0.046). Meta-analysis of those four case-control studies on CYP2E1 rs3813867 polymorphism showed that there was no significant association between CYP2E1 rs3813867 polymorphism and colorectal cancer risk under all contrast models (c2 versus c1: OR = 0.96, 95 % CI 0.80-1.16, P = 0.672; c2c2 versus c1c1: OR = 1.26, 95 % CI 0.43-3.67, P = 0.672; c2c2/c1c2 versus c1c1: OR = 0.95, 95 % CI 0.78-1.16, P = 0.114; and c2c2 versus c1c2/c1c1: OR = 1.17, 95 % CI 0.41-3.36, P = 0.775). Therefore, the findings from this meta-analysis suggest that CYP2E1 rs2031920 polymorphism is associated with colorectal cancer risk, but CYP2E1 rs3813867 polymorphism is not associated with colorectal cancer risk. In addition, more well-designed studies with large sample size are needed to provide a more precise evaluation on the associations above.
Collapse
Affiliation(s)
- Hui Peng
- Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, SunYat-sen University, 26 Yuancun Heng 2 Road, Guangzhou, 510655, Guangdong, China
| | | | | | | |
Collapse
|
|
11
|
Lanara Z, Giannopoulou E, Fullen M, Kostantinopoulos E, Nebel JC, Kalofonos HP, Patrinos GP, Pavlidis C. Comparative study and meta-analysis of meta-analysis studies for the correlation of genomic markers with early cancer detection. Hum Genomics 2013; 7:14. [PMID: 23738773 PMCID: PMC3686617 DOI: 10.1186/1479-7364-7-14] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Accepted: 05/01/2013] [Indexed: 12/12/2022] Open
Abstract
A large number of common disorders, including cancer, have complex genetic traits, with multiple genetic and environmental components contributing to susceptibility. A literature search revealed that even among several meta-analyses, there were ambiguous results and conclusions. In the current study, we conducted a thorough meta-analysis gathering the published meta-analysis studies previously reported to correlate any random effect or predictive value of genome variations in certain genes for various types of cancer. The overall analysis was initially aimed to result in associations (1) among genes which when mutated lead to different types of cancer (e.g. common metabolic pathways) and (2) between groups of genes and types of cancer. We have meta-analysed 150 meta-analysis articles which included 4,474 studies, 2,452,510 cases and 3,091,626 controls (5,544,136 individuals in total) including various racial groups and other population groups (native Americans, Latinos, Aborigines, etc.). Our results were not only consistent with previously published literature but also depicted novel correlations of genes with new cancer types. Our analysis revealed a total of 17 gene-disease pairs that are affected and generated gene/disease clusters, many of which proved to be independent of the criteria used, which suggests that these clusters are biologically meaningful.
Collapse
Affiliation(s)
- Zoi Lanara
- Faculty of Mathematical, Physical and Natural Sciences, Department of Biological Sciences, University of Trieste, Trieste, 34128, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
12
|
CYP2E1 T7632A and 9-bp insertion polymorphisms and colorectal cancer risk: a meta-analysis based on 4,592 cases and 5,918 controls. Tumour Biol 2013; 34:2225-31. [PMID: 23636797 DOI: 10.1007/s13277-013-0762-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 03/22/2013] [Indexed: 12/21/2022] Open
Abstract
UNLABELLED Previous studies suggest that genetic factors play important roles in the development of colorectal cancer. CYP2E1 T7632A and 9-bp insertion polymorphisms may influence the risk of colorectal cancer, but published results are conflicting. We therefore conducted a meta-analysis comprising 9 case-control studies with 4,592 cases and 5,918 controls. Odds ratios (ORs) with 95 % confidence interval (95 % CI) were used to assess the strength of the associations of CYP2E1 T7632A and 9-bp insertion polymorphisms with colorectal cancer. For CYP2E1 T7632A polymorphism, meta-analysis showed that there was no significant association between the CYP2E1 T7632A polymorphism and colorectal cancer risk under all contrast models (A vs. T: OR = 1.06, 95 % CI 0.88-1.29, P = 0.528; AA vs. TT: OR = 0.85, 95 % CI 0.61-1.19, P = 0.351; AA/TA vs. TT: OR = 1.08, 95 % CI 0.87-1.34, P = 0.484; and AA vs. TT/TA OR = 0.87, 95 % CI 0.62-1.21, P = 0.395). For CYP2E1 96-bp insertion polymorphism, meta-analysis showed that there was a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk under the allele contrast model and the dominant contrast model (for the allele contrast model: OR = 1.20, 95 % CI 1.06-1.36, P = 0.005; for the dominant contrast model: OR = 1.25, 95 % CI 1.07-1.45, P = 0.005). Subgroup analysis by race suggested that there was an obvious association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk in Asians under the codominant contrast model. In conclusion, our meta-analysis demonstrates that there is a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk, and CYP2E1 9-bp insertion polymorphism is a risk factor for developing colorectal cancer.
Collapse
|
|
13
|
Jiang O, Zhou R, Wu D, Liu Y, Wu W, Cheng N. CYP2E1 polymorphisms and colorectal cancer risk: a HuGE systematic review and meta-analysis. Tumour Biol 2013; 34:1215-24. [PMID: 23355335 DOI: 10.1007/s13277-013-0664-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Accepted: 01/11/2013] [Indexed: 01/28/2023] Open
Abstract
Studies investigating the associations between Cytochrome P4502E1 (CYP2E1) polymorphisms and colorectal cancer (CRC) risk report conflicting results. We conducted a meta-analysis to assess the association between CYP2E1 gene Rsa I/Pst I, Dral T/A and 96-bp insertion polymorphisms and CRC susceptibility. Two investigators independently searched the Medline, Embase, CNKI, Wanfang, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for CYP2E1 polymorphisms and CRC were calculated in a fixed-effect model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Ultimately, 12, 5, and 4 studies were found to be eligible for meta-analyses of Rsa I/Pst I, Dral T/A, and 96-bp insertion polymorphisms, respectively. Our analysis suggested that the variant genotype of Rsa I/Pst I were associated with a significantly increased CRC risk (c2/c2 vs. c1/c1, OR = 1.36, 95 % CI = 1.04-1.77; recessive model, OR = 1.35, 95 % CI = 1.04-1.75). Moreover, similar results were observed between CYP2E1 96-bp insertion polymorphism and CRC risk (dominant model, OR = 1.25, 95 % CI = 1.07-1.45), while no association was observed between CYP2E1 Dral T/A polymorphism and CRC susceptibility in any genetic model. No publication bias was found in the present study. This meta-analysis shows that CYP2E1 Rsa I/Pst I and 96-bp insertion polymorphisms may be associated with CRC risk. The CYP2E1 Dral T/A polymorphism was not detected to be related to the risk for CRC.
Collapse
Affiliation(s)
- Ou Jiang
- Department of Surgical Oncology, The Second People's Hospital of Neijiang, 244 Xin Jiang Road, Neijiang, 641100, Sichuan Province, China
| | | | | | | | | | | |
Collapse
|