The contribution of ABCG2 G34A and C421A polymorphisms to multiple myeloma susceptibility

Katarzyna Niebudek, Ewa Balcerczak, Marek Mirowski, Jacek Pietrzak, Izabela Zawadzka, Marta Żebrowska-Nawrocka Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interfaculty Cathedral of Laboratory and Molecular Diagnostics, Medical University of Lodz, Lodz 90-151, Poland Background: Breast cancer resistance protein BCRP, belonging to superfamily G of the adenosine triphosphate-binding cassette (ABC) transporters, is an efflux pump and plays a critical role in protecting cells against xenobiotics and toxic compounds including (pro)carcinogens. BCRP is expressed in many tissues, including hematopoietic stem cells. Genetic variants such as single nucleotide polymorphisms (SNPs) can change the gene expression and/or reduce their products’ activity which may affect an individual’s susceptibility to xenobiotics and the development of carcinoma. These changes may affect the exposure of blood cells to toxic compounds, which increases the risk of multiple myeloma. The aim of this study was to determine polymorphisms at positions G34A and C421A of the ABCG2 gene in multiple myeloma in the Polish population for the first time. Materials and methods: Material for the study included DNA isolated from nucleus of cells of peripheral blood of patients diagnosed with multiple myeloma (investigated group N=181) and from healthy people (control group N=97). Research into the polymorphisms was conducted using the polymerase chain reaction-restriction fragment length polymorphism technique. Results: The present study showed a statistically significant association between SNP C421A of the ABCG2 gene and the risk of developing multiple myeloma (P=0.0218). No statistically significant relationship was found for the other parameters analyzed, such as age, gender, or type of secreted immunoglobulin. Conclusion: Preliminary studies indicate that SNP C421A may become a potential predictor for the development of multiple myeloma. Keywords: BCRP, polymorphism, ABCG2, multiple myeloma risk, plasma cell myeloma, single nucleotide polymorphis