Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array

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dc.contributor.authorKalra, Sourav
dc.contributor.authorKaur, Raman Preet
dc.contributor.authorLudhiadch, Abhilash
dc.contributor.authorShafi, Gowhar
dc.contributor.authorVashista, Rajesh
dc.contributor.authorKumar, Raj
dc.contributor.authorMunshi, Anjana
dc.date.accessioned2018-07-14T01:18:35Z
dc.date.accessioned2024-08-14T07:41:08Z
dc.date.available2018-07-14T01:18:35Z
dc.date.available2024-08-14T07:41:08Z
dc.date.issued2018
dc.description.abstractPurpose: Cyclophosphamide and doxorubicin (adjuvant chemotherapy) are commonly used to treat breast cancer patients. Variation in the genes involved in pharmacodynamics and pharmacokinetics of these drugs plays an important role in prediction of drug response and survival. The present study was carried out with an aim to evaluate the variation in all the genes involved in pharmacokinetic and pharmacodynamics pathways of cyclophosphamide and doxorubicin, and correlate specific variants with disease outcome in breast cancer patients from the Malwa region of Punjab. Methods: A total of 250 confirmed breast cancer patients were involved in the study. Genotyping was performed on an Illumina Infinium HD assay platform using a Global Screening Array (GSA) microchip. GenomeStudio (Illumina, Inc.) was used for data preprocessing and a p value less than or equal to 5 ? 10?8 was considered statistically significant. To rule out the influence of confounding risk factors, a step-wise multivariate regression analysis was carried out to evaluate the association of genotype with overall clinical outcome. Results: Two gene variants, CYP2C19 (G681A) and ALDH1A1*2 (17 bp deletion), were found to be significantly associated with the disease outcome, including overall survival, recurrence and metastasis, in breast cancer patients on adjuvant therapy. Both these genes are involved in the pharmacokinetics of cyclophosphamide. However, none of the variants in the genes involved in pharmacokinetics and pharmacodynamics of doxorubicin were found to have any significant impact on disease outcome in the studied group. Conclusion: CYP2C19 (G681A) variant and ALDH1A1*2 emerged as two important biomarkers associated with bad outcome in breast cancer patients on adjuvant therapy. ? 2018 Springer-Verlag GmbH Germany, part of Springer Natureen_US
dc.identifier.citationKalra, S., Kaur, R. P., Ludhiadch, A., Shafi, G., Vashista, R., Kumar, R., & Munshi, A. (2018). Association of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening array. European Journal of Clinical Pharmacology, 1-8. doi: 10.1007/s00228-018-2505-6en_US
dc.identifier.doi10.1007/s00228-018-2505-6
dc.identifier.issn316970
dc.identifier.urihttp://10.2.3.109/handle/32116/1242
dc.identifier.urlhttps://link.springer.com/article/10.1007%2Fs00228-018-2505-6
dc.language.isoenen_US
dc.publisherSpringer Verlagen_US
dc.titleAssociation of CYP2C19*2 and ALDH1A1*1/*2 variants with disease outcome in breast cancer patients: results of a global screening arrayen_US
dc.title.journalEuropean Journal of Clinical Pharmacology
dc.typeArticle in Pressen_US

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