Impact of ALDH1A1 and NQO1 gene polymorphisms on the response and toxicity of chemotherapy in Bangladeshi breast cancer patients.
ALDH1A1
NQO1
Breast cancer
Polymorphism
Response
Toxicity
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
16 Jul 2024
16 Jul 2024
Historique:
received:
13
08
2022
accepted:
05
07
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
16
7
2024
Statut:
aheadofprint
Résumé
Cyclophosphamide, Epirubicin/Doxorubicin, 5-fluorouracil (CEF or CAF) chemotherapy has long been a standard first-line treatment for breast cancer. The genetic variations of enzymes that are responsible for the metabolism of these drugs have been linked to altered treatment response and toxicity. Two drug-metabolizing enzymes ALDH1A1 and NQO1 are critically involved in the pathways of CEF/CAF metabolism. This study aimed to evaluate the effect of ALDH1A1 (rs13959) and NQO1 (rs1800566) polymorphisms on treatment response and toxicities caused by adjuvant (ACT) and neoadjuvant chemotherapy (NACT) where CEF/CAF combination was used to treat Bangladeshi breast cancer patients. A total of 330 patients were recruited from various hospitals, with 150 receiving neoadjuvant chemotherapy and 180 receiving adjuvant chemotherapy. To extract genomic DNA, a non-enzymatic simple salting out approach was adopted. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect genetic polymorphisms. Unconditional logistic regression was used to derive odds ratios (ORs) with 95% confidence intervals (CIs) to study the association between genetic polymorphisms and clinical outcome and toxicity. A statistically significant association was observed between ALDH1A1 (rs13959) polymorphism and treatment response (TT vs. CC: aOR = 6.40, p = 0.007; recessive model: aOR = 6.38, p = 0.002; allele model: p = 0.032). Patients with the genotypes TT and CT + TT of the NQO1 (rs1800566) polymorphism had a significantly higher risk of toxicities such as anemia (aOR = 0.34, p = 0.006 and aOR = 0.58, p = 0.021), neutropenia (aOR = 0.42, p = 0.044 and aOR = 0.57, p = 0.027), leukopenia (aOR = 0.33, p = 0.010 and aOR = 0.46, p = 0.005), and gastrointestinal toxicity (aOR = 0.30, p = 0.02 and aOR = 0.38, p = 0.006) when compared to the wild CC genotype, while patients with the genotype CT had a significant association with gastrointestinal toxicity (aOR = 0.42, p = 0.02) and leukopenia (aOR = 0.52, p = 0.010). The TT and CT + TT genotypes of rs13959 had a significantly higher risk of anemia (aOR = 2.00, p = 0.037 and aOR = 1.68, p = 0.029). There was no significant association between rs1800566 polymorphism and treatment response. Polymorphisms in ALDH1A1 (rs13959) and NQO1 (rs1800566) may be useful in predicting the probability of treatment response and adverse effects from CEF or CAF-based chemotherapy in breast cancer patients.
Identifiants
pubmed: 39012380
doi: 10.1007/s00280-024-04700-5
pii: 10.1007/s00280-024-04700-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Southeast University
ID : Southeast University
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Aziz MA, Akter T, Sarwar MS, Islam MS (2022) The first combined meta-analytic approach for elucidating the relationship of circulating resistin levels and RETN gene polymorphisms with colorectal and breast cancer. Egypt J Med Hum Genet 23:27. https://doi.org/10.1186/s43042-022-00240-w
doi: 10.1186/s43042-022-00240-w
Benson JR, Jatoi I (2012) The global breast cancer burden. Future Oncol 8:697–702. https://doi.org/10.2217/fon.12.61
doi: 10.2217/fon.12.61
pubmed: 22764767
WHO (2021) Breast cancer. https://www.who.int/news-room/fact-sheets/detail/breast-cancer [Accessed: December 21, 2021]
Bangladesh (2021) The International Agency for Research on Cancer. THE GLOBAL CANCER OBSERVATORY 1–2. https://gco.iarc.fr/today/data/factsheets/populations/50-bangladesh-fact-sheets.pdf [Accessed 21 May 2022]
Anadolu Agency (2021) Central database, mass awareness to address breast cancer in Bangladesh. https://www.aa.com.tr/en/asia-pacific/central-database-mass-awareness-to-address-breast-cancer-in-bangladesh/2401288 [Accessed 21 May 2022]
Cura Y, Ramírez CP, Martín AS et al (2021) Genetic polymorphisms on the effectiveness or safety of breast cancer treatment: clinical relevance and future perspectives. Rev Mutat Res 788:108391. https://doi.org/10.1016/j.mrrev.2021.108391
doi: 10.1016/j.mrrev.2021.108391
Moo TA, Sanford R, Dang C, Morrow M (2018) Overview of breast Cancer therapy. PET clin 13:339–354. https://doi.org/10.1016/j.cpet.2018.02.006
doi: 10.1016/j.cpet.2018.02.006
pubmed: 30100074
pmcid: 6092031
Miteva-Marcheva NN, Ivanov HY, Dimitrov DK, Stoyanova VK (2020) Application of pharmacogenetics in oncology. Biomark Res 8:32. https://doi.org/10.1186/s40364-020-00213-4
doi: 10.1186/s40364-020-00213-4
pubmed: 32821392
pmcid: 7429778
Stearns V, Davidson NE, Flockhart DA (2004) Pharmacogenetics in the treatment of breast cancer. Pharmacogenomics J 4:143–153. https://doi.org/10.1038/sj.tpj.6500242
doi: 10.1038/sj.tpj.6500242
pubmed: 15024382
Weinshilboum R (2003) Inheritance and drug response. NEJM 348:529–537. https://doi.org/10.1056/nejmra020021
doi: 10.1056/nejmra020021
pubmed: 12571261
Wiechec E, Hansen LL (2009) The effect of genetic variability on drug response in conventional breast cancer treatment. Eur J Pharmacol 625:122–130. https://doi.org/10.1016/j.ejphar.2009.08.045
doi: 10.1016/j.ejphar.2009.08.045
pubmed: 19836373
Chawla R, Rani V, Mishra M, Kumar K (2021) Integrated Role of Nanotechnology and Pharmacogenetics in diagnosis and treatment of diseases. Pharmacogenetics IntechOpen. https://doi.org/10.5772/intechopen.97643
doi: 10.5772/intechopen.97643
Balkhi B, Alqahtani S, Altayyar W et al (2020) Drug utilization and expenditure of anticancer drugs for breast cancer. SPJ 28:669–674. https://doi.org/10.1016/j.jsps.2020.04.007
doi: 10.1016/j.jsps.2020.04.007
pubmed: 32550797
pmcid: 7292878
Zhang J, Tian Q, Zhou SF (2006) Clinical pharmacology of Cyclophosphamide and Ifosfamide. Curr Drug ther 1:55–84
doi: 10.2174/157488506775268515
Huang Q, Feng L, Li H, Zheng L, Qi X, Wang Y (2020) Jian-Pi-Bu-Xue-Formula alleviates Cyclophosphamide-Induced Myelosuppression via Up-Regulating NRF2/HO1/NQO1 signaling. Front Pharmacol 1302. https://doi.org/10.3389/fphar.2020.01302
Nebert DW, Roe AL, Vandale SE, Bingham E, Oakley GG (2002) NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: a HuGE review. Genet Med 4:62–70. https://doi.org/10.1097/00125817-200203000-00003
doi: 10.1097/00125817-200203000-00003
pubmed: 11882782
Islam M, Islam MS, Parvin S et al (2015) Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients. Tumour Biol 36:5451–5457. https://doi.org/10.1007/s13277-015-3211-y
doi: 10.1007/s13277-015-3211-y
pubmed: 25677905
Glorieux C, Calderon PB (2019) Cancer Cell sensitivity to Redox-Cycling Quinones is influenced by NAD(P)H: Quinone Oxidoreductase 1 polymorphism. Antioxidants 8:369. https://doi.org/10.3390/antiox8090369
doi: 10.3390/antiox8090369
pubmed: 31480790
pmcid: 6770057
Nagata M, Kimura T, Suzumura T, Kira Y, Nakai T, Umekawa K (2013) C609T polymorphism of NADPH quinone oxidoreductase 1 correlates clinical hematological toxicities in lung cancer patients treated with amrubicin. Clin Med Insights Oncol 31–40. https://doi.org/10.4137/CMO.S10839
Akhtari FS, Green AJ, Small GW, Havener TM, House JS, Roell KR (2021) High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs. PLoS Genet 17:e1009732. https://doi.org/10.1371/journal.pgen.1009732
doi: 10.1371/journal.pgen.1009732
pubmed: 34437536
pmcid: 8439493
Shortall K, Djeghader A, Magner E, Soulimane T (2021) Insights into Aldehyde dehydrogenase enzymes: a structural perspective. Front Mol Biosci 8:659550. https://doi.org/10.3389/fmolb.2021.659550
doi: 10.3389/fmolb.2021.659550
pubmed: 34055881
pmcid: 8160307
Townsend AJ, Leone-Kabler S, Haynes RL, Wu Y, Szweda L, Bunting KD (2001) Selective protection by stably transfected human ALDH3A1 (but not human ALDH1A1) against toxicity of aliphatic aldehydes in V79 cells. Chem Biol Interact 130:261–273. https://doi.org/10.1016/S0009-2797(00)00270-2
doi: 10.1016/S0009-2797(00)00270-2
pubmed: 11306050
Yang L, Ren Y, Yu X et al (2014) ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma. Mod Pathol 27:775–783. https://doi.org/10.1038/modpathol.2013.189
doi: 10.1038/modpathol.2013.189
pubmed: 24201124
Kalra S, Kaur RP, Ludhiadch A et al (2018) Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array. Eur J Clin Pharmacol 74:1291–1298. https://doi.org/10.1007/s00228-018-2505-6
doi: 10.1007/s00228-018-2505-6
pubmed: 29938344
Helsby NA, Yong M, van Kan M, de Zoysa JR, Burns KE (2019) The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes. Br J Clin Pharmacol 85:1925–1934. https://doi.org/10.1111/bcp.14031
doi: 10.1111/bcp.14031
pubmed: 31218720
pmcid: 6710526
Ekhart C, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD (2008) Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin. Pharmacogenet Genomics 18:1009–1015. https://doi.org/10.1097/FPC.0b013e328313aaa4
doi: 10.1097/FPC.0b013e328313aaa4
pubmed: 18854779
Yao S, Sucheston LE, Zhao H et al (2014) Germline genetic variants in ABCB1, ABCC1 and ALDH1A1, and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer. Pharmacogenomics J 14:241–247. https://doi.org/10.1038/tpj.2013.32
doi: 10.1038/tpj.2013.32
pubmed: 23999597
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur Jour Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026
doi: 10.1016/j.ejca.2008.10.026
National Institutes of Health (2017) Protocol Development | CTEP. Cancer.gov. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm [Accessed 1 Jan. 2022]
Islam MS, Ahmed MU, Sayeed MS et al (2013) Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population. Clin Chim Acta 416:11–19. https://doi.org/10.1016/j.cca.2012.11.011
doi: 10.1016/j.cca.2012.11.011
pubmed: 23178447
Parvin MN, Aziz MA, Rabbi SNI et al (2021) Assessment of the link of ABCB1 and NR3C1 gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: a genotype and haplotype approach. J Adv Res 33:141–151. https://doi.org/10.1016/j.jare.2021.02.001
doi: 10.1016/j.jare.2021.02.001
pubmed: 34603785
pmcid: 8463901
Zhang J, Schulz WA, Li Y et al (2003) Association of NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with esophageal squamous cell carcinoma in a German caucasian and a northern Chinese population. Carcinogenesis 24(5):905–909. https://doi.org/10.1093/carcin/bgg019
doi: 10.1093/carcin/bgg019
pubmed: 12771035
Jamieson D, Cresti N, Bray J, Sludden J, Griffin MJ, Hawsawi NM, Famie E, Mould EV, Verrill MW, May FE, Boddy AV (2011) Two minor NQO1 and NQO2 alleles predict poor response of breast cancer patients to adjuvant doxorubicin and cyclophosphamide therapy. Pharmacogenet Genomics 21(12):808–819. https://doi.org/10.1097/FPC.0b013e32834b6918
doi: 10.1097/FPC.0b013e32834b6918
pubmed: 21946896
Chaturvedi P, Tulsyan S, Agarwal G et al (2015) Relationship of MTHFR and NQO1 pharmacogenetics and chemotherapy clinical outcomes in breast Cancer patients. Biochem Genet 53(7–8):211–222. https://doi.org/10.1007/s10528-015-9683-z
doi: 10.1007/s10528-015-9683-z
pubmed: 26014925
Fojo T, Coley HM (2007) The role of Efflux pumps in Drug-resistant metastatic breast Cancer: New insights and Treatment strategies. Clin Breast Cancer 7:749–756. https://doi.org/10.3816/CBC.2007.n.035
doi: 10.3816/CBC.2007.n.035
pubmed: 18021475
Wang Z, Liang S, Lian X et al (2015) Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Sci Rep 5:9301. https://doi.org/10.1038/srep09301
doi: 10.1038/srep09301
pubmed: 25818003
pmcid: 4377623
Cao J, Zhang M, Wang B, Zhang L, Fang M, Zhou F (2021) Chemoresistance and metastasis in breast Cancer Molecular mechanisms and Novel Clinical Strategies. Front Oncol 11:658552. https://doi.org/10.3389/fonc.2021.658552
doi: 10.3389/fonc.2021.658552
pubmed: 34277408
pmcid: 8281885
Meyer UA, Zanger UM (1997) Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol 37:269–296. https://doi.org/10.1146/annurev.pharmtox.37.1.269
doi: 10.1146/annurev.pharmtox.37.1.269
pubmed: 9131254
Low SK, Kiyotani K, Mushiroda T, Daigo Y, Nakamura Y, Zembutsu H (2009) Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients. J Hum Genet 54:564–571. https://doi.org/10.1038/jhg.2009.79
doi: 10.1038/jhg.2009.79
pubmed: 19696793
Delforge M, Ludwig H (2017) How I manage the toxicities of myeloma drugs. Blood 129:2359–2367. https://doi.org/10.1182/blood-2017-01-725705
doi: 10.1182/blood-2017-01-725705
pubmed: 28275090
Feinberg B, Kish J, Dokubo I, Wojtynek J, Gajra A, Lord K (2020) Comparative effectiveness of Palliative Chemotherapy in metastatic breast Cancer: a real-world evidence analysis. Oncologist 25:319–326. https://doi.org/10.1634/theoncologist.2019-0699
doi: 10.1634/theoncologist.2019-0699
pubmed: 31951300
pmcid: 7160410
Gradishar WJ, Anderson BO, Abraham J et al (2020) Breast Cancer, Version 3.2020, NCCN Clinical Practice guidelines in Oncology. JNCCN 18:452–478. https://doi.org/10.6004/jnccn.2020.0016
doi: 10.6004/jnccn.2020.0016
pubmed: 32259783
Michael M, Doherty MM (2005) Tumoral Drug Metabolism: overview and its implications for Cancer Therapy. J Clin Oncol 23:205–229. https://doi.org/10.1200/jco.2005.02.120
doi: 10.1200/jco.2005.02.120
pubmed: 15625375
Diasio RB, Johnson MR (1999) Dihydropyrimidine dehydrogenase: its role in 5-fluorouracil clinical toxicity and tumor resistance. Clin Cancer Res 5:2672–2673
pubmed: 10537327
Dutour R, Cortés-Benítez F, Roy J, Poirier D (2017) Structure-based design and synthesis of New Estrane–pyridine derivatives as cytochrome P450 (CYP) 1B1 inhibitors. ACS Med Chem 8:1159–1164. https://doi.org/10.1021/acsmedchemlett.7b00265
doi: 10.1021/acsmedchemlett.7b00265
Verma H, Bahia MS, Choudhary S, Singh PK, Silakari O (2019) Drug metabolizing enzymes-associated chemo resistance and strategies to overcome it. Drug Metab Rev 51:196–223. https://doi.org/10.1080/03602532.2019.1632886
doi: 10.1080/03602532.2019.1632886
pubmed: 31203662
Yadav A, Gupta A, Rastogi N et al (2016) Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival. Tumour Biol 37:1835–1844. https://doi.org/10.1007/s13277-015-3929-6
doi: 10.1007/s13277-015-3929-6
pubmed: 26318430
Siegel D, Anwar A, Winski SL, Kepa JK, Zolman KL, Ross D (2001) Rapid Polyubiquitination and Proteasomal Degradation of a mutant form of NAD(P)H:Quinone Oxidoreductase 1. Mol Pharmacol 59:263–268. https://doi.org/10.1124/mol.59.2.263
doi: 10.1124/mol.59.2.263
pubmed: 11160862
Yadav U, Kumar P, Rai V (2018) NQO1 gene C609T polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer risk: a Meta-analysis. Nutr Cancer 70:557–568. https://doi.org/10.1080/01635581.2018.1460674
doi: 10.1080/01635581.2018.1460674
pubmed: 29652514
Megías-Vericat JE, Martínez-Cuadrón D, Herrero MJ et al (2021) Influence of polymorphisms in anthracyclines metabolism genes in the standard induction chemotherapy of acute myeloid leukemia. Pharmacogenet Genomics 31:133–139. https://doi.org/10.1097/FPC.0000000000000431
doi: 10.1097/FPC.0000000000000431
pubmed: 33675324
Fagerholm R, Hofstetter B, Tommiska J et al (2008) NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nat Genet 40:844–853. https://doi.org/10.1038/ng.155
doi: 10.1038/ng.155
pubmed: 18511948