Multiple myeloma (MM) cells interact with bone marrow stromal cells
stimulating transcription and secretion of cytokines like IL-6 and IL-10,
which are implicated in the progression and dissemination of MM. Regulation
of cytokines secretion is under genetic control through genetic polymorphisms
in their coding and promoter sequences. It seems that single nucleotide
polymorphism (SNP) in the promoter region of various genes may regulate the
plasma concentrations of cytokines. Cytokines could be also hypothesized to
function as pain modulators as peripheral nociceptors are sensitized by
cytokines. The aim was to determine if the SNP of IL-6 and IL-10 cytokines
could influence the analgesic response of radiotherapy in the treatment of
painful bone destructions in MM patients. 30 patients (19 women and 11 men,
median age: 67 years) with MM and painful bone destructions were treated with
palliative radiotherapy. Pain was evaluated according to the visual analogue
scale and analgesics intake. Pain scores and analgesics use were measured
prior to radiotherapy as well as 4, 12 and 24 weeks afterward. Opioid
analgesics were converted to the morphine-equivalent daily dose (MEDD).
Genomic DNA was extracted from peripheral blood leukocytes and IL-6 and IL-10
gene promoter polymorphisms were analysed with polymerase chain reaction. 60%
of patients reported severe pain prior to radiotherapy, which decreased to
13% at the first follow-up visit (p <0.001). The MEDD on admission to the
hospital was 75 mg/day which decreased to 46 mg/day at the first follow-up
visit (p = 0.033). A significant parameter in pain relief was: age < 65 years
(p=0.029). We analysed 6 SNPs in the gene promoter region of IL-6 (-597 G/A,
-572 G/C, -174 G/C) and IL-10 (-592 A/C, -819 C/T, -1082 A/G) as well as
their relation with pain severity and analgesic consumption. Patients who are
IL-10 -1082 A/G carriers are prone to respond better to radiotherapy than
other patients (p<0.05). A borderline association was noted for patients who
are IL-6 -597 A/A and G/G carriers - assumed to be at higher risk for severe
pain prior to radiotherapy (p=0.07) while for patients who are IL-10 - 1082
A/A carries: the median pain score decreased faster (p=0.08). Patients with
genotypes IL-6 -597 A/A and IL-6 -174 C/C required a smaller dose of opioids
(p=0.06). SNP of IL-6 and IL-10 cytokines can influence the analgesic
response of radiotherapy. Patients with genotype IL-10 -1082 A/G respond
better to radiotherapy.
Matrix metalloproteinase 9 gene promoter region -1562 C/T single nucleotide polymorphism increases the susceptibility to hypertensive disorders of pregnancy: a meta-analysis
