Association between the COMT Val158Met polymorphism and risk of cancer: evidence from&amp;nbsp;99 case&amp;ndash;control studies

Zhou, Quan; Wang, Yan; Chen, Aihua; Tao, Yaling; Song, Huamei; Li, Wei; Tao, Jing; Zuo, Mingzhang

doi:10.2147/ott.s90883

Cited by 10 publications

(5 citation statements)

References 98 publications

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“…COMT-Val158Met-polymorphism has been intensively studied. Associations have been found with the susceptibility and appearance of cognitive phenotypes, psychiatric disorders, changes in brain activation and structure, and cancer susceptibility [ 15 , 16 ]. Furthermore, links between COMT genotypes and the increased risk of coronary events or the outcome of patients with ischemic heart disease were revealed [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease

Mir

Bhat

Javid

et al. 2018

JCDD

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Purpose: Catechol-O-methyltransferase (COMT) plays a central role in DNA repair and estrogen-induced carcinogenesis. The nonsynonymous single nucleotide polymorphism (SNP) in exon 4 G > A or Val108 > 158Met or rs4680 G > A influences COMT enzyme activity. The three phenotypes of the COMT enzyme activities include COMT A/A with low enzyme activity, COMT A/G with medium enzyme activity and COMT G/G with high enzyme activity. The Met allele is associated with low enzymatic activity resulting in higher levels of prefrontal dopamine. Conversely, the Val allele is associated with high enzymatic activity and lower levels of prefrontal dopamine. The Met allele has been associated with several psychiatric disorders such as panic disorder. Many recent epidemiologic studies have investigated the association between the COMT Val158Met polymorphism and coronary artery diseases risk, but the results are inconclusive. Therefore our study was aimed to explore the association between COMT Val158Met polymorphism and the risk of coronary artery disease in India. Methology: This study was conducted on 100 clinically confirmed cases of coronary artery diseases and 100 healthy controls. COMT Val158Met genotyping was performed by allele-specific polymerase chain reaction (AS-PCR). Results: A significant correlation was observed in the COMT Val158Met genotype distribution between the coronary artery disease cases and healthy controls (p = 0.008). The frequencies of all three genotypes, GG, GA, AA, reported in the CAD patients were 10%, 70%, and 20%, and 30%, 60%, and 10% in the healthy controls respectively. An increased risk of coronary artery disease was observed in the codominant inheritance model for COMT-GA vs. GG genotype with an OR of 3.5, 95% CI (1.58–7.74) p = 0.002) and COMT-AA vs. GG genotype with an OR of 6.0 95% CI (2.11–17.3) p = 0.003). The higher risk of coronary artery disease was observed in the dominant inheritance model for COMT (GA + AA) vs. GG genotype (OR 3.85, 95% CI 1.76–8.4, p < 0.007), whereas a non-significant association was found in recessive model for COMT (GG + GA vs. AA) (OR = 2.01, 95% CI (0.86–4.7) p = 0.72). The results indicated that A allele significantly increased the risk of coronary artery disease compared to the G allele (OR = 1.8, 95% CI (1.20–2.67) p = 0.004). COMT Val158Met polymorphism leads to a 6.0, 3.5 and 1.8-fold increased risk of developing coronary artery disease in the Indian population and providing novel insights into the genetic etiology and underlying biology of coronary artery disease. Conclusions: It is concluded that COMT-AA genotype and A allele are significantly associated with an increased susceptibility to coronary artery disease in Indian population. A larger sample size can be the key to progress in establishing the genetic co-relationship of COMT polymorphism and cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease

Mir

Bhat

Javid

et al. 2018

JCDD

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“…COMT polymorphism is associated with the risk of lung cancer in non-smoking women [58]. Previous reports have shown that polymorphisms of COMT played a role in the risk of esophageal cancer [57,59], lung cancer [58], breast cancer [60][61][62], prostate cancer [63], and bladder cancer [59,64]. Although these reports focused on the respective cancers, there is little to no research on the relationship between COMT gene polymorphisms and oral and pharyngeal cancer risk, particularly in OPMD.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Proteinic Linkage of MAO and COMT with Oral Potentially Malignant Disorders and Cancers of the Oral Cavity and Pharynx

Chen

Lan

et al. 2021

Cancers

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Betel quid (BQ), a group I human carcinogen, strongly contributes to an increased risk of oral potentially malignant disorders (OPMD) and cancers of the oral cavity and pharynx. This study was conducted to discover whether monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) variants play a potential role in the risk assessment of oral cavity and pharynx cancers and OPMD, particularly among BQ users. We applied a case–control study to confirm the polymorphism of MAO and COMT using single-nucleotide polymorphisms. We used qRT-PCR, Western blotting, and immunohistochemistry (IHC) to determine MAO and COMT expression. Carriers of the MAOA rs6323 G-allele, MAOB rs6324 G-allele, and COMT rs4633 C/C-genotype had a prominently increased risk of oral cavity and pharynx cancers (AOR = 56.99; p < 0.001). Compared to adjacent noncancerous tissues, a significant downregulation of MAO and COMT expression was exhibited in cancerous tissues (p < 0.01). Furthermore, in different cell models, MAO and COMT expression was significantly downregulated with an increased dose of arecoline (p < 0.01). In personalized preventive medicine for oral and pharyngeal cancers, our findings are the first to demonstrate the potential role of lower MAO and COMT expression levels, with the risk polymorphisms utilized as clinical biomarkers.

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“…The single nucleotide polymorphism (SNP) G>A (rs4680) leads to an amino acid change of Val to Met in the position 108/158 in cytoplasmic/ membranous enzyme form, Submit your Manuscript | www.austinpublishinggroup.com respectively, and is generally known as Val158Met. This SNP has important (two-to fivefold) impact on the enzymatic activity as those individuals homozygous for the Val (GG) have high activity enzyme variant, those with Met/Met (AA) possess low activity protein and heterozygous genotype carriers (Val/Met, GA) have the enzyme form with intermediate activity [7,12,14,17,[19][20][21][22][23][24][25][26][27][28]. It means that alteration in the respective genotype leads to the change in efficacy of O-methylation of different endogenous and exogenous catecholic compounds (including for example catechol estrogens, but also flavonoids like quercetin, fisetin and different flavanols) and therefore also to the increased amounts of circulating catechols with significantly different bioactivities compared to their O-methylated metabolites.…”

Section: Discussionmentioning

confidence: 99%

Change of COMT Val158Met Genotype in Tumoral B Cells of a Chronic Lymphocytic Leukemia Patient: A Case Report

Sak¹

2017

Ann Hematol Oncol

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In this case report, a Chronic lymphocytic leukemia (CLL) female patient with a heterozygous polymorphism in the catechol-O-methyltransferase (COMT) gene is described. This functional change in the COMT enzyme Val158Met leads to a decreased efficacy to O-methylate different endogenous and exogenous compounds containing catechol structure, including hydroxylated estradiol intermediates, catecholamines and certain dietary flavonoids. The specific change found in tumoral B-cells as compared to the genomic DNA from the non-B fraction of peripheral blood mononuclear cells of the patient, could indicate that Val158Met might play some role in the pathogenesis of CLL that certainly needs further investigations. The possible application of this polymorphism as a potential biomarker of CLL is also worth of further largescale case-control studies. Keywords: Biomarker; Catechol-O-methyltransferase; Chronic lymphocytic leukemia; O-methylation Case PresentationThe venous blood sample was taken from a 64-year-old woman within a regular check-up. The patient had a 7-year history of chronic lymphocytic leukemia (B-CLL; Rai stage 1 and Binet stage A disease) and her hematological status was stable. As patient did not have any B symptoms, anemia or thrombocytopenia and she did not need any specific treatment according to the current CLL management approaches. Laboratorial findings revealed the white blood cell count (WBC) of 30x10 9 /L with lymphocyte count of 25x10 9 /L. Phenotype of the lymphocytes was determined as CD45+, CD19+, CD20+, CD5+, CD23+, CD43+, CD38-, FMC7-, CD79b-. Lymph nodes were observed only in cervical region with the diameter less than 1 cm. Fluorescence in situ hybridization revealed the presence of a monoallelic 13q deletion. The IGHV status of the patient as well as the expression of ZAP70 was not studied.Peripheral blood mononuclear cells (PBMCs) were further separated from the whole blood sample using a density gradient technique (Ficoll-Paque TM Premium, GE Healthcare). B cells were isolated from PBMCs by the human B-CLL Cell Isolation Kit from MACS Miltenyi Biotec. DNA was separated from whole blood sample, B cells and non-B fraction of PBMCs using QIAamp DNA Mini Kit (Qiagen) and the respective concentrations were determined by NanoDrop 2000C spectrophotometer (Thermo Scientific). Because of the recent increasing interest in possible role of phase II enzymes and their genetic variants in carcinogenesis [1], the fourth exon of catechol-O-methyltransferase (COMT) gene was amplified by polymerase chain reaction (PCR) and the COMT Val158Met (rs4680, G>A) genotype was determined by restriction analysis using FastDigest NIaIII (Hin1II, Thermo Scientific) as the restriction enzyme. Standard gel picture of three different genotypes Special Article -Acute and Chronic Myeloid Leukemia

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Association between the COMT Val158Met polymorphism and risk of cancer: evidence from 99 case–control studies

Cited by 10 publications

References 98 publications

Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease

Potential Impact of COMT-rs4680 G > A Gene Polymorphism in Coronary Artery Disease

Genetic and Proteinic Linkage of MAO and COMT with Oral Potentially Malignant Disorders and Cancers of the Oral Cavity and Pharynx

Change of COMT Val158Met Genotype in Tumoral B Cells of a Chronic Lymphocytic Leukemia Patient: A Case Report

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