MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic outcome

P-glycoprotein (PGP), the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of carcinogens and cytostatics. It has been suggested that MDR1 polymorphisms contribute to the variability in cancer risk and therapeutic outcome. We examined the relevance of C3435T polymorphism...

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Bibliographic Details
Published in:	The pharmacogenomics journal Vol. 10; no. 1; pp. 62 - 69
Main Authors:	Cizmarikova, M, Wagnerova, M, Schonova, L, Habalova, V, Kohut, A, Linkova, A, Sarissky, M, Mojzis, J, Mirossay, L, Mirossay, A
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-02-2010 Nature Publishing Group
Subjects:	Adult Aged Aged, 80 and over Alleles Analysis Anthracycline Anthracyclines Anthracyclines - adverse effects Anthracyclines - therapeutic use ATP Binding Cassette Transporter, Sub-Family B ATP-Binding Cassette, Sub-Family B, Member 1 - genetics Biomedical and Life Sciences Biomedicine Breast cancer Breast carcinoma Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Carcinogens Chemotherapy Disease Progression Female Gene Expression Gene Frequency Genetic aspects Health aspects Hematologic Diseases - chemically induced Homozygotes Human Genetics Humans MDR1 protein Middle Aged Neoadjuvant Therapy Oncology original-article P-Glycoprotein Patient outcomes Pharmacogenetics Pharmacotherapy Polymorphism Polymorphism, Single Nucleotide Population genetics Psychopharmacology Retrospective Studies Risk Factors Treatment Outcome P-glycoprotein toxicity therapeutic outcome breast cancer polymorphism anthracycline
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Summary:	P-glycoprotein (PGP), the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of carcinogens and cytostatics. It has been suggested that MDR1 polymorphisms contribute to the variability in cancer risk and therapeutic outcome. We examined the relevance of C3435T polymorphism in relation to breast cancer susceptibility, clinical and pathological characteristics of breast carcinoma, the therapeutic response and hematologic toxicities after anthracycline-based chemotherapy. A significant association between allele frequencies and histological type, stage and histological grade was observed ( P =0.024, 0.014, 0.006, respectively, χ 2 -test or Fisher's exact test). We also found significantly higher ( P =0.019, χ 2 -test) T allele frequency in breast cancer patients ( n =221) than in controls ( n =113). A significantly enhanced therapeutic outcome after neoadjuvant therapy ( n =38; P =0.021, Fisher's exact test) and longer time to progression after anthracycline-based chemotherapy ( n =102; P =0.049, log-rank test) were observed in CC homozygotes. However, no significant association between hematologic toxicities and C3435T polymorphism was detectable.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1470-269X 1473-1150
DOI:	10.1038/tpj.2009.41