|
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
|
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
|
|
3
|
Pan B, Xia Y, Fang S, Ai J, Wang K, Zhang J, Du C, Chen Y, Liu L, Yan S. Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction. Front Pharmacol 2022; 13:1043252. [PMID: 36313348 PMCID: PMC9607907 DOI: 10.3389/fphar.2022.1043252] [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: 09/13/2022] [Accepted: 09/28/2022] [Indexed: 12/01/2022] Open
Abstract
Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWD on CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions.
Collapse
Affiliation(s)
- Boyu Pan
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, ITCWM Hospital, Tianjin University, Tianjin, China
- Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Yafei Xia
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, ITCWM Hospital, Tianjin University, Tianjin, China
| | - Senbiao Fang
- Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Jun Ai
- Department of Laboratory Animal Science, Tianjin Medical University, Tianjin, China
| | - Kunpeng Wang
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Tianjin Medical University, Tianjin, China
| | - Jian Zhang
- Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Chunshuang Du
- Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Yuzhou Chen
- Department of Pharmaceutics, College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Shu Yan, ; Liren Liu, ; Yuzhou Chen,
| | - Liren Liu
- Department of Molecular Pharmacology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- *Correspondence: Shu Yan, ; Liren Liu, ; Yuzhou Chen,
| | - Shu Yan
- Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, ITCWM Hospital, Tianjin University, Tianjin, China
- *Correspondence: Shu Yan, ; Liren Liu, ; Yuzhou Chen,
| |
Collapse
|
|
4
|
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
|
|
5
|
Xu S, Zhang F, Chen D, Su K, Zhang L, Jiang R. In vitro inhibitory effects of ganoderic acid A on human liver cytochrome P450 enzymes. PHARMACEUTICAL BIOLOGY 2020; 58:308-313. [PMID: 32285742 PMCID: PMC7178866 DOI: 10.1080/13880209.2020.1747500] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
Context: Ganoderic acid A (GAA) is usually used to prevent cancers or other diseases, which make it likely to be used with other drugs metabolized by cytochromes P450.Objective: This study investigates the effect of GAA on eight major cytochrome P450 isoforms in human liver microsomes.Material and method: The effects of GAA (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific substrates for the CYPs, and the enzyme kinetic parameters were calculated.Results: The results showed that GAA inhibited the activity of CYP3A4, 2D6, and 2E1, but did not affect other isoforms. The inhibition of CYP3A4, 2D6, and 2E1 was concentration-dependent with IC50 values of 15.05, 21.83, and 28.35 μM, respectively. Additionally, GAA was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2D6 and 2E1, with Ki values of 7.16, 10.07, and 13.45 μM. Meanwhile, the inhibition of CYP3A4 was time-dependent, with the KI/Kinact value of 7.91/0.048 μM/min.Discussion and conclusion: The in vitro study indicated that GAA has the potential to result in drug-drug interactions with other drugs metabolized by CYP3A4, 2D6, and 2E1. Further clinical studies are needed for the identification of this interaction.
Collapse
Affiliation(s)
- Shangchen Xu
- Department of Neurosurgery, Shandong Provincial Hospital, Jinan, Shandong, China
| | - Fengqing Zhang
- Department of Tumor Intervention, Municipal Official Hospital of WeiFang, Weifang, Shandong, China
| | - Dali Chen
- Department of Laboratory, Yidu Central Hospital of Weifang, Weifang, Shandong, China
| | - Keren Su
- Department of Pharmacy, Shanxian Central Hospital (Affiliated Huxi Hospital of Jining Medical University), Heze, Shandong, China
| | - Li Zhang
- Department of Pharmacy, Shanxian Central Hospital (Affiliated Huxi Hospital of Jining Medical University), Heze, Shandong, China
| | - Rui Jiang
- Department of Minimally Invasive Tumor, Shandong Provincial Hospital, Jinan, Shandong, China
- CONTACT Rui Jiang Department of Minimally Invasive Tumor, Shandong Provincial Hospital, No. 324, Jingweuweiqi Road, Jinan, Shandong250000, China
| |
Collapse
|
|
6
|
Li M, Liu X, Wang Y, Ju X. In vitro effects of peimine on the activity of cytochrome P450 enzymes. Xenobiotica 2020; 50:1202-1207. [PMID: 32338127 DOI: 10.1080/00498254.2020.1761572] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Peimine is a major component of Fritillaria ussuriensis, which is a widely used herb in pediatric. It is very common in Chinese traditional medicine to combine with two or more herbs in the clinic. To investigate the effect of peimine on the activity of cytochrome P450 enzymes (CYP450) is necessary for the clinical application of peimine.The effects of peimine on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro in human liver microsomes (HLMs) with the specific inhibitors as positive control and without peimine or inhibitors as negative control. The enzyme kinetic parameters were calculated.It was found that peimine inhibited the activity of CYP3A4, 2E1, and 2D6 in a concentration-dependent manner with the IC50 values of 13.43, 21.93, and 22.46 μM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the Ki value of 6.49 μM, and the inhibition of CYP2E1 and 2D6 was performed in a competitive manner with Ki values of 10.76 and 11.95 μM. Additionally, peimine inhibited the activity of CYP3A4 in a time-dependent manner with the KI/Kinact value of 6.17/0.049 min-1 μM-1.Peimine inhibited the activity of CYP3A4, 2E1, and 2D6, which indicated the potential interaction between peimine and drugs metabolized by CYP3A4, 2E1, and 2D6. Further studies are needed to verify the drug-drug interaction and the in vivo effects.
Collapse
Affiliation(s)
- Meng Li
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Xiaoyan Liu
- Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, China
| | - Yuzhen Wang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Xiuli Ju
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| |
Collapse
|
|
7
|
Tan SC. Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition. J Gene Med 2018; 20:e3010. [PMID: 29424105 DOI: 10.1002/jgm.3010] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 01/12/2018] [Accepted: 01/19/2018] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer is a leading form of cancer in both males and females. Early detection of individuals at risk of colorectal cancer allows proper treatment and management of the disease to be implemented, which can potentially reduce the burden of colorectal cancer incidence, morbidity and mortality. In recent years, the role of genetic susceptibility factors in mediating predisposition to colorectal cancer has become more and more apparent. Identification of high-frequency, low-penetrance genetic polymorphisms associated with the cancer has therefore emerged as an important approach which can potentially aid prediction of colorectal cancer risk. However, the overwhelming amount of genetic epidemiology data generated over the past decades has made it difficult for one to assimilate the information and determine the exact genetic polymorphisms that can potentially be used as biomarkers for colorectal cancer. This review comprehensively consolidates, based primarily on results from meta-analyses, the recent progresses in the search of colorectal cancer-associated genetic polymorphisms, and discusses the possible mechanisms involved.
Collapse
Affiliation(s)
- Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| |
Collapse
|
|
8
|
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]
|
|
9
|
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
|
|
10
|
Fang Z, Wu Y, Zhang N. Association between CYP2E1 genetic polymorphisms and urinary cancer risk: a meta-analysis. Oncotarget 2017; 8:86853-86864. [PMID: 29156840 PMCID: PMC5689730 DOI: 10.18632/oncotarget.20993] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 08/29/2017] [Indexed: 12/19/2022] Open
Abstract
Objective Studies investigating the contribution of Cytochrome P4502E1 (CYP2E1) polymorphisms to the etiology of urinary cancer draw inconsistent conclusions. Thus, we performed a meta-analysis to evaluate the association between CYP2E1 Rsa I/Pst I and Dra I polymorphisms and urinary cancer susceptibility. Materials and Methods Meta-analysis based on the eligible case-control studies that assess the association of CYP2E1 Rsa I/Pst I and Dra I polymorphisms with urinary cancer was conducted. Subgroup analyses based on ethnicity and cancer type were also carried out. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the associations between the two polymorphisms. Funnel plot and Begg’s test were used for publication bias diagnosis. Results We found decreased urinary cancer risk among subjects carrying CYP2E1 RsaI/PstI c1c2 + c2c2 genotype and c2 allele (OR = 0.73, 95% CI = 0.68–0.79 and OR = 0.79, 95% CI = 0.74–0.85, respectively), with 3,301 cases and 3,786 controls from 14 studies. We also observed a significant difference in c1c2 + c2c2 vs. c1c1 and c2 vs. c1 among Asians (OR = 0.68, 95% CI = 0.60–0.78 and OR = 0.75, 95% CI = 0.66–0.85, respectively). However, the meta-analysis based on 5 eligible studies showed no significant association between CYP2E1 Dra I polymorphism and urinary cancer susceptibility in either dominant model or the allele model. Conclusions Our meta-analysis concluded that CYP2E1 Rsa I/Pst I polymorphism correlates with urinary cancers risk in Asian population; while CYP2E1 Dra I polymorphism might be not significantly associated with the urinary cancer risks. Large and well-designed studies are needed to confirm these results.
Collapse
Affiliation(s)
- Zhiqing Fang
- Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yun Wu
- Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ning Zhang
- Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| |
Collapse
|
|
11
|
Hartman JH, Miller GP, Meyer JN. Toxicological Implications of Mitochondrial Localization of CYP2E1. Toxicol Res (Camb) 2017; 6:273-289. [PMID: 28989700 DOI: 10.1039/c7tx00020k] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Cytochrome P450 2E1 (CYP2E1) metabolizes an extensive array of pollutants, drugs, and other small molecules, often resulting in bioactivation to reactive metabolites. Therefore, it is unsurprising that it has been the subject of decades of research publications and reviews. However, while CYP2E1 has historically been studied in the endoplasmic reticulum (erCYP2E1), active CYP2E1 is also present in mitochondria (mtCYP2E1). Relatively few studies have specifically focused on mtCYP2E1, but there is growing interest in this form of the enzyme as a driver in toxicological mechanisms given its activity and location. Many previous studies have linked total CYP2E1 to conditions that involve mitochondrial dysfunction (fasting, diabetes, non-alcoholic steatohepatitis, and obesity). Furthermore, a large number of reactive metabolites that are formed by CYP2E1 through metabolism of drugs and pollutants have been demonstrated to cause mitochondrial dysfunction. Finally, there appears to be significant inter-individual variability in targeting to the mitochondria, which could constitute a source of variability in individual response to exposures. This review discusses those outcomes, the biochemical properties and toxicological consequences of mtCYP2E1, and highlights important knowledge gaps and future directions. Overall, we feel that this exciting area of research is rich with new and important questions about the relationship between mtCYP2E1, mitochondrial dysfunction, and pathology.
Collapse
Affiliation(s)
| | - Grover P Miller
- Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Joel N Meyer
- Nicholas School of the Environment, Duke University, Durham, NC
| |
Collapse
|
|
12
|
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: 13] [Impact Index Per Article: 1.4] [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
|
|
13
|
Abstract
Esophageal cancer (EC) is one of the most common malignancies in low- and medium-income countries and represents a disease of public health importance because of its poor prognosis and high mortality rate in these regions. The striking variation in the prevalence of EC among different ethnic groups suggests a significant contribution of population-specific environmental and dietary factors to susceptibility to the disease. Although individuals within a demarcated geographical area are exposed to the same environment and share similar dietary habits, not all of them will develop the disease; thus genetic susceptibility to environmental risk factors may play a key role in the development of EC. A wide range of xenobiotic-metabolizing enzymes are responsible for the metabolism of carcinogens introduced via the diet or inhaled from the environment. Such dietary or environmental carcinogens can bind to DNA, resulting in mutations that may lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are all subject to genetic polymorphisms that can lead to altered expression or activity of the encoded proteins. Genetic polymorphisms may, therefore, act as molecular biomarkers that can provide important predictive information about carcinogenesis. The aim of this review is to discuss our current knowledge on the genetic risk factors associated with the development of EC in different populations; it addresses mainly the topics of genetic polymorphisms, gene-environment interactions, and carcinogenesis. We have reviewed the published data on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and discuss some of the potential gene-environment interactions underlying esophageal carcinogenesis. The main enzymes discussed in this review are the glutathione S-transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs), sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide hydrolases (EHs), all of which have key roles in the detoxification of environmental and dietary carcinogens. Finally, we discuss recent advances in the study of genetic polymorphisms associated with EC risk, specifically with regard to genome-wide association studies, and examine possible challenges of case-control studies that need to be addressed to better understand the interaction between genetic and environmental factors in esophageal carcinogenesis.
Collapse
Affiliation(s)
- Marco Matejcic
- a International Centre for Genetic Engineering and Biotechnology, Cape Town Component , Observatory , Cape Town , South Africa , and
| | | |
Collapse
|
|
14
|
Mittal B, Tulsyan S, Kumar S, Mittal RD, Agarwal G. Cytochrome P450 in Cancer Susceptibility and Treatment. Adv Clin Chem 2015; 71:77-139. [PMID: 26411412 DOI: 10.1016/bs.acc.2015.06.003] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cytochrome 450 (CYP450) designates a group of enzymes abundant in smooth endoplasmic reticulum of hepatocytes and epithelial cells of small intestines. The main function of CYP450 is oxidative catalysis of various endogenous and exogenous substances. CYP450 are implicated in phase I metabolism of 80% of drugs currently in use, including anticancer drugs. They are also involved in synthesis of various hormones and influence hormone-related cancers. CYP450 genes are highly polymorphic and their variants play an important role in cancer risk and treatment. Association studies and meta-analyses have been performed to decipher the role of CYP450 polymorphisms in cancer susceptibility. Cancer treatment involves multimodal therapies and evaluation of CYP450 polymorphisms is necessary for pharmacogenetic assessment of anticancer therapy outcomes. In addition, CYP450 inhibitors are being evaluated for improved pharmacokinetics and oral formulation of several anticancer drugs.
Collapse
Affiliation(s)
- Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
| | - Sonam Tulsyan
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Surendra Kumar
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Rama Devi Mittal
- Department of Urology and Renal Transplant, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Gaurav Agarwal
- Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| |
Collapse
|
|
15
|
Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 2014; 134:2403-2413. [PMID: 24122750 DOI: 10.1002/ijc.28536] [Citation(s) in RCA: 334] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 09/19/2013] [Accepted: 09/30/2013] [Indexed: 12/12/2022]
Abstract
The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta-analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression-free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.
Collapse
Affiliation(s)
- Mu-Xing Li
- Research Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
Gao J, Kang AJ, Lin S, Dai ZJ, Zhang SQ, Liu D, Zhao Y, Yang PT, Wang M, Wang XJ. Association between MDM2 rs 2279744 polymorphism and breast cancer susceptibility: a meta-analysis based on 9,788 cases and 11,195 controls. Ther Clin Risk Manag 2014; 10:269-277. [PMID: 24790452 PMCID: PMC3999277 DOI: 10.2147/tcrm.s60680] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
PURPOSE Previous studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and cancer risk. The aim of this study was to evaluate the relationship between the MDM2 rs 2279744 polymorphism and the susceptibility of breast cancer. METHODS We searched PubMed, Web of Knowledge, Embase, and the Chinese National Knowledge Infrastructure (CNKI) database for case-control studies published up to October 2013 that investigated MDM2 rs 2279744 polymorphism and breast cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of these associations. RESULTS A total of 19 studies were identified for the meta-analysis, including 9,788 cases and 11,195 controls. The variant heterozygote (TG) was associated with breast cancer risk in the overall population (TG vs TT: OR =1.10, 95% CI =1.04-1.17, P=0.001, P=0.23 for heterogeneity test). In the subgroup analyses by ethnicity, a significantly increased risk was observed among Asians (G vs T: OR =1.12, 95% CI =1.02-1.23, P=0.02, P het=0.04; GG vs TT: OR =1.29, 95% CI =1.06-1.56, P=0.01, P het=0.04; TG vs TT: OR =1.36, 95% CI =1.15-1.60, P=0.0004, P het=0.45; dominant model TG+GG vs TT: OR =1.21, 95% CI =1.03-1.41, P=0.02, P het=0.07). However, among Caucasians, rs 2279744 was associated with breast cancer risk in only one genotype (TG vs TT: OR =1.09, 95% CI =1.00-1.18, P=0.04, P het=0.37). No publication bias was found in the present study. CONCLUSION This meta-analysis provides evidence for the association between the MDM2 rs 2279744 polymorphism and breast cancer susceptibility. The results suggest that the MDM2 rs 2279744 polymorphism plays an important role in breast cancer, especially in Asians.
Collapse
Affiliation(s)
- Jie Gao
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
- Department of Nephrology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - An-Jing Kang
- Department of Pathology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Shuai Lin
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Zhi-Jun Dai
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Shu-Qun Zhang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Di Liu
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Yang Zhao
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Peng-Tao Yang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Meng Wang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Xi-Jing Wang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| |
Collapse
|
|
17
|
Zhao H, Zhu F, Sun J, Meng X. Meta-analysis of the association between NQO1 Pro187Ser polymorphism and colorectal cancer in Asians. Tumour Biol 2013; 35:2111-6. [PMID: 24142528 DOI: 10.1007/s13277-013-1280-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2013] [Accepted: 09/27/2013] [Indexed: 01/12/2023] Open
Abstract
There were a number of studies performed to assess the association between NQO1 Pro187Ser polymorphism and colorectal cancer risk in Asians, but no consensus was available up to now. We conducted a meta-analysis to assess the association between NQO1 Pro187Ser polymorphism and colorectal cancer risk in Asians. Case-control studies investigating the association between NQO1 Pro187Ser polymorphism and colorectal cancer risk in Asians were searched in Pubmed and Wanfang databases. Pooled odds ratio (OR) and 95% confidence interval (95% CI) was calculated. Finally, seven studies involving a total of 2,051 cases and 2,798 controls met the inclusion criteria and were included into the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and colorectal cancer risk in Asians (Ser versus Pro: OR = 1.42, 95% CI 1.08-1.87, P = 0.013; SerSer versus ProPro: OR = 1.86, 95% CI 1.08-3.19, P = 0.024; SerSer/ProSer versus ProPro: OR = 1.61, 95% CI 1.10-2.35, P = 0.014; SerSer versus ProPro/ProSer: OR = 1.46, 95% CI 1.02-2.10, P = 0.041). There was low risk of publication bias in the meta-analysis. This meta-analysis suggests that there is an obvious association between NQO1 Pro187Ser polymorphism and colorectal cancer risk in Asians.
Collapse
Affiliation(s)
- Hang Zhao
- Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200097, China
| | | | | | | |
Collapse
|
|
18
|
SMAD7 rs12953717 polymorphism contributes to increased risk of colorectal cancer. Tumour Biol 2013; 35:695-9. [PMID: 23949881 DOI: 10.1007/s13277-013-1095-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 08/07/2013] [Indexed: 02/07/2023] Open
Abstract
Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism has been implicated to alter the risk of colorectal cancer (CRC), but the results are controversial. The objective of this study was to quantitatively evaluate the association between SMAD7 rs12953717 polymorphism and CRC susceptibility. A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and CRC risk. Pooled odds ratio and 95% confidence interval were calculated using a fixed or random effects model. Statistical analysis was performed with Review Manager 5.0 and Stata 11. A total of 11 case-control studies, including 12,058 cases and 11,444 controls, were identified. The combined results based on all studies suggested that rs12953717 was associated with CRC risk under all genetic models. When stratifying for race, the data showed that the rs12953717 was associated with a significantly increased CRC risk under all genetic models in Caucasians. Statistically significant association was found in all genetic models except in recessive model comparison in the subgroup of Asians. After stratifying the studies by study design, there was a significant association between rs12953717 polymorphism and CRC risk under all genetic models in the subgroup of population-based studies. Our study suggests that rs12953717 polymorphism is associated with an increased CRC risk.
Collapse
|
|
19
|
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
|