CYP2D6 gene polymorphisms and breast cancer risk in Moroccan population: A case-control study

Elouilamine, Ezohra; Akil, Soumaya El; Aznag, Fatima Zahra; Izaabel, El Hassan

doi:10.1016/j.genrep.2020.100768

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…According to our results, an increased CYP2D6*3 (Null allele metabolizer) allelic frequency was observed in Moroccan population compared to others. This allele was found to be associated with acute lymphoblastic leukemia and breast cancer disease [53,57]. A similar CYP2D6*3 allele frequency was also observed within Brazilians.…”

Section: Discussionsupporting

confidence: 65%

“…The CYP2D6 enzyme is implicated in the metabolism of a wide range of clinically used drugs, such as tamoxifen. Many investigations reported an association of CYP2D6 genetic polymorphisms with susceptibility and response to treatment in many diseases such as autoimmune conditions, cardiovascular diseases and several cancers [52][53][54][55][56][57]. Furthermore, clinical studies reported that CYP2D6 genetic polymorphisms are associated with adverse responses to many drugs such as opioids including codeine, antiarrhythmic drugs and anti-cancer drugs [11][12][13].…”

Section: Discussionmentioning

confidence: 99%

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Explore the distribution of (rs35742686, rs3892097 and rs1065852) genetic polymorphisms of cytochrome P4502D6 gene in the Moroccan population

Akil

Elouilamine

Ighid

et al. 2022

Egypt J Med Hum Genet

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Background The CYP2D6 gene encodes a crucial enzyme involved in the metabolic pathways of many commonly used drugs. It is a highly polymorphic gene inducing an interethnic and interindividual variability in disease susceptibility and treatment response. The aim of this study is to evaluate the frequency of the three CYP2D6 most investigated alleles (CYP2D6*3, CYP2D6*4, and CYP2D6*10 alleles) in Morocco compared to other populations. This study enrolled 321 healthy Moroccan subjects. CYP2D6 genotypes and allele frequencies were assessed using a restriction fragment length polymorphism–polymerase chain reaction genotyping method. The Principal Component Analysis (PCA) and dendrogram were conducted to evaluate genetic proximity between Moroccans and other populations depending on CYP2D6 allele frequencies. Results According to the current study, the results observed the homozygous wild type of the three studied SNPs were predominant among the Moroccan population, while 1.4% of Moroccans carried the CYP2D6*4 allele responsible for a Poor Metabolizer phenotype and associated with low enzyme activity which may induce a treatment failure. The PCA and cluster dendrogram tools revealed genetic proximity between Moroccans and Mediterranean, European and African populations, versus a distancing from Asian populations. Conclusion The distribution of CYP2D6 polymorphisms within Morocco follows the patterns generally found among the Mediterranean, European and African populations. Furthermore, these results will help to lay a basis for clinical studies, aimed to introduce and optimize a personalized therapy in the Moroccan population.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Explore the distribution of (rs35742686, rs3892097 and rs1065852) genetic polymorphisms of cytochrome P4502D6 gene in the Moroccan population

Akil

Elouilamine

Ighid

et al. 2022

Egypt J Med Hum Genet

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“…Generally, CYP2D6 is not directly related to any disease, and the average allelic frequencies for each ethnic group provided by the Pharmacogenomics Knowledge Base (PharmGKB) were calculated based on studies of both healthy and patient individuals [ 33 , 34 ]. However, CYP2D6 is involved in metabolizing and detoxifying numerous xenobiotics [ 35 ] and some of the included studies have proved a linkage between CYP2D6 genetic polymorphisms and susceptibility to diseases [ 12 – 14 , 17 , 19 ]. Therefore, in the absence of profound evidence, we here reported the frequency of each CYP2D6 allele in the overall population rather than only healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Frequencies of CYP2D6 genetic polymorphisms in Arab populations

et al. 2022

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CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevant CYP2D6 alleles in the Arabs countries. Articles published before May 2021 that reported CYP2D6 genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. Active CYP2D6 gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function allele CYP2D6*4 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D6*10 allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function allele CYP2D6*41 was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity of CYP2D6 alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine their CYP2D6 allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.

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STAT3 gene polymorphisms and susceptibility to breast cancer in the Moroccan population

Ighid,

El Akil,

Izaabel

2023

Egypt J Med Hum Genet

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Background Breast cancer is a complex disease due to its extremely complicated and varied etiology. It is found to be linked to improper transcription factor activation that interferes with normal breast development. Among these factors, signal transducer and activator of transcription (STAT) proteins play a crucial role in regulating gene expression and cell signaling. Specifically, STAT3, a member of the STAT family, has been found to be constitutively active in various cancer types, including breast cancer. Three STAT3 SNPs (rs744166, rs229152, and rs4796793) were widely investigated in association with cancer diseases in many populations, yet the findings were conflicting. This study seeks to evaluate the association risk of these three SNPs with breast cancer in Moroccan women. Materials and methods This case–control study consisted of 200 breast cancer cases and 200 age- and sex-matched healthy controls. The extraction was carried out from whole blood by the salting-out method. Genotypes were defined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and sequence-specific primer–polymerase chain reaction (SSP–PCR) methods. Results In the over-dominant model (GG–CC vs. GC), the rs4796793*GC genotype was linked to a higher risk of breast cancer among triple-negative cases. Additionally, a significant association has been revealed between HER2 and the mutant genotype of the two polymorphisms rs744166 and rs4796793. Moreover, the STAT3 rs744166*AG genotype was less common in cases with late-stage (grade III) disease. Conclusion These findings suggest that STAT3 polymorphisms are associated with triple-negative breast cancer and HER2+ type; the top two lethal breast cancer in Moroccans.

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CYP2D6 gene polymorphisms and breast cancer risk in Moroccan population: A case-control study

Cited by 4 publications

References 30 publications

Explore the distribution of (rs35742686, rs3892097 and rs1065852) genetic polymorphisms of cytochrome P4502D6 gene in the Moroccan population

Explore the distribution of (rs35742686, rs3892097 and rs1065852) genetic polymorphisms of cytochrome P4502D6 gene in the Moroccan population

Frequencies of CYP2D6 genetic polymorphisms in Arab populations

STAT3 gene polymorphisms and susceptibility to breast cancer in the Moroccan population

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