Association of Chromosome 17 Aneuploidy, Deletion, Expression and Its rs1042522 Variant with Multiple Myeloma Risk and Response to Thalidomide/Bortezomib Treatment.

Multiple myeloma (MM) is a multifactorial genetic disorder caused by interactive effects of environmental and genetic factors. The proper of the gene (17p13.1) and its protein is essential in genomic stability. The most common variant of the gene-p.P72R (rs1042522)-shows functional variation. The aim of our study was a complex analysis of the p.P72R variant and gene expression in relation to chromosomal changes of the gene , as well as MM risk and outcome. Genomic DNA from 129 newly diagnosed MM patients was analyzed by methods of automated DNA sequencing (for variant analysis) and cIg-FISH (for chromosomal aberrations analysis). RNA was used in real-time PCR to determine the expression. In MM patients, the variant was not in Hardy-Weinberg equilibrium. The RR genotype was associated with lower MM risk (OR = 0.44, = 0.004). A higher number of plasma cells was found in patients with RR genotype in comparison to those with PP + PR genotypes (36.74% vs. 28.30%, = 0.02). A higher expression of the gene was observed in PP + PR genotypes vs. RR homozygote ( < 0.001), in smokers vs. non-smokers ( = 0.02). A positive Pearson's correlation was found between the expression level and the number of plasma cells (r = 0.26, = 0.04). The presence of chromosome 17 aberrations with or without did not affect the MM risk and outcome. Similar results were observed in the case of gene expression and the p.P72R variant.