Molecular genetics of plasma cell myeloma rs1045642 in P-glycoprotein : from genome to proteome in plasma cell myeloma

• Main Author: Drain, Stephen
• Published: University of Ulster 2010
• Subjects: 616.994
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.551591

Multidrug resistance (MDR) is a phenomenon in malignancy whereby tumour cells generate mechanisms to resist cytotoxic treatments and previous research has demonstrated that a prominent cause of this resistance is via the expression and activity of certain protein within the surface of the cell. However these proteins also have natural expression and function which must be taken into account when considering the true impact of these proteins in cancer. The aim of this thesis was to determine the impact of a single nucleotide polymorphism (rs1045642) on the activity of the most studied of these proteins, P-glycoprotein (P-gp) in plasma cell myeloma (PCM). The results of the studies within this thesis have demonstrated that genotype at rs1045642 mediates an advantage in overall survival, that it may indeed affect P-gp activity in PCM and that these effects are independent of two further polymorphisms which display a high degree of genetic synergy with rs1045642. Furthermore, evidence is presented in this thesis that P-gp mediated drug resistance in PCM may be due primarily to its natural intestinal expression and that ABCB4 may be a more prominent contributor to tumour cell drug efflux in PCM.