Abstract
Chemotherapeutics are commonly used in the treatment of breast cancer, adjuvant to surgery and in the treatment of metastatic disease. However the ability of cancer cells to become resistant to different drugs remains a major impediment to successful chemotherapy. It is a major challenge in the improvement of cancer treatment to be able to predict and circumvent drug resistance. Multidrug resistance may be caused by several mechanisms including genetic variants in the multidrug resistance gene, MDR1, encoding a drug efflux pump, and glutathione s-transferases, GSTs, encoding detoxifying enzymes. The following study aimed to reveal an association between different MDR1 haplotypes and GST genotypes and TP53 mutation status and response to treatment with doxorubicin in Norwegian breast cancer patients. A previously documented association of a variant GSTP1 allele with occurrence of mutations in the TP53 gene was confirmed. The study also revealed that carriers of certain genotypes of MDR1 exon 26 had a higher frequency of TP53 mutations. Further, a polymorphism in exon 11 of GSTP1 and one in exon 26 of MDR1 was found to be associated with TP53 mutation status. MDR1 haplotypes were shown to be unevenly distributed between the control and case groups, and even to be case and control specific. Significantly poorer survival was shown for the carriers of the case-frequent haplotypes as compared with the patients with control-frequent haplotypes.