Evidence map›Paper›PMID 39012380›Full record

ArticleCancer chemotherapy and pharmacology2024

Impact of ALDH1A1 and NQO1 gene polymorphisms on the response and toxicity of chemotherapy in Bangladeshi breast cancer patients.

Md Siddiqul Islam, Ferdowsi Akter, Md Mosiqur Rahman, Md Rajdoula Rafe, Md Abdul Aziz, Salma Parvin, Abu Syed Md Mosaddek, Mohammad Safiqul Islam, Md Wahid Akter

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Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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5 · Who and what money

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9 authors.

Md Siddiqul IslamDepartment of Pharmacy, Southeast University, Dhaka, 1213, Bangladesh.
Ferdowsi AkterDepartment of Pharmacy, Southeast University, Dhaka, 1213, Bangladesh.
Md Mosiqur RahmanDepartment of Pharmacy, Southeast University, Dhaka, 1213, Bangladesh.
Md Rajdoula RafeDepartment of Pharmacy, Jagannath University, Dhaka, 1100, Bangladesh.
Md Abdul AzizDepartment of Pharmacy, State University of Bangladesh, Dhaka, 1205, Bangladesh.
Salma ParvinQUEST Bangladesh - Biomedical Research Centre, Dhaka, 1230, Bangladesh.
Abu Syed Md MosaddekQUEST Bangladesh - Biomedical Research Centre, Dhaka, 1230, Bangladesh.
Mohammad Safiqul IslamDepartment of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali, 3814, Bangladesh. research_safiq@yahoo.com.ORCID 0000-0003-4924-5319
Md Wahid AkterDepartment of Radiation Oncology, National Institute of Cancer Research & Hospital (NICRH), Dhaka, 1212, Bangladesh.

Funding

Southeast University Southeast University
6 · The paper itself

Abstract

purposeCyclophosphamide, 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.

methodsA 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.

resultsA 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.

conclusionPolymorphisms 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.

Indexed as

Aldehyde Dehydrogenase 1 FamilyAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCyclophosphamideFluorouracilNAD(P)H Dehydrogenase (Quinone)Neoadjuvant TherapyRetinal DehydrogenaseAdultAgedBangladeshChemotherapy, AdjuvantDoxorubicinEpirubicinFemaleGenotypeAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanCyclophosphamideDoxorubicinEpirubicinFluorouracilNAD(P)H Dehydrogenase (Quinone)NQO1 protein, humanRetinal DehydrogenaseALDH1A1Breast cancerNQO1PolymorphismResponseToxicity

Identifiers

PMID39012380

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