BackgroundInterleukin-10 and tumor necrosis factor α play an important role in breast carcinogenesis. Genes, encoding those two cytokines, contain single nucleotide polymorphisms, which are associated with differential levels of gene transcription. This study analyzes single nucleotide polymorphisms in interleukin 10 and tumor necrosis factor α genes and their contribution to breast cancer phenotype, lymph node status and survival in a group of young Lithuanian women with early-stage breast cancer patients.ResultsWe genotyped 100 premenopausal Eastern European (Lithuanian) patients with stage I-II breast cancer, ≤50 years old at the time of diagnosis, for interleukin 10 -592A > C, −819C > T and -1082A > G and tumor necrosis factor α -308G > A single nucleotide polymorphisms in the gene promoter region. We used the polymerase chain reaction, namely a restriction fragment length polymorphism method, for a SNP analysis. All genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the HapMap CEU population. Holders of IL10 -592A > C heterozygous IL10 -592 AC genotype had a higher probability of estrogen receptor positive breast cancer phenotype than homozygous variants (P = 0.017). Phased ACC haplotype of IL10 polymorphisms was associated with younger age of diagnosis (P = 0.017). Of all the tested single nucleotide polymorphisms, only TNFα -308G > A has revealed a prognostic capability for breast cancer survival. GA genotype carriers, compared to GG, showed a significant disadvantage in progression-free survival (P = 0.005, adjusted hazard ratio (HR) = 4.631, 95 % confidence interval (CI) = 1.587 – 13.512), metastasis-free survival (P = 0.010, HR = 4.708, 95 % CI = 1.445 – 15.345) and overall survival (P = 0.037, HR = 4.829, 95 % CI = 1.098 – 21.243).ConclusionsAccording to our data, IL10 -1082A > G, −819 T > C, −592A > C polymorphisms and phased haplotypes have not revealed a prognostic value for breast cancer. On the contrary, the TNFα -308 polymorphism might modulate the risk and contribute to the identification of patients at a higher risk of breast cancer recurrence, metastasis and worse overall survival among young Lithuanian early-stage breast cancer patients.
Objective: Conventional serologic typing of red blood cell systems other than ABO and RhD can be inaccurate and difficult to interpret in patients who have recently undergone blood transfusion. While molecular-based assays are not used routinely, the usefulness of genotyping was investigated in order to determine patients who may benefit from this procedure. Materials and Methods: Blood samples were taken from 101 patients with haemato-oncological, chronic renal, or gastroenterological diseases and from 50 donor controls; the samples were tested for Fya and Fyb by applying serologic and genetic methods. All patients had received 3 or more units of RBCs during the last 3 months. An average of 6.1 RBC units were transfused per patient. The average length of time from transfusion until blood sampling was 24.4 days. The haemagglutination test was applied for serological analysis, and the restriction length polymorphism assay was used for genotyping.Results: In total, 33 (32.7%) patients showed positive reactions with anti-Fya or anti-Fyb while being negative genetically. False-positive Fya results were found in 23 samples, and false-positive Fyb in 10 specimens. During the last 3 months, significantly more RBC units were transfused to patients with discrepant results than to those with accurate phenotyping/genotyping results: median of 5 (mean ± SE: 6.85±0.69) versus median of 4 (mean: 5.71±0.51), respectively (p=0.025). The median length of time after the last transfusion was 25 days (mean: 28.72±2.23 days) in the group with accurate phenotyping/genotyping results versus a median of 14 days (mean: 15.52±1.95 days) in the group with discrepant results (p=0.001). Phenotypes and genotypes coincided in all donor samples.Conclusion: Genotyping assays for the Duffy system should be considered if the patient underwent blood transfusion less than 3 or 4 weeks before the sample collection. If the time frame from RBC transfusion exceeds 6 weeks, Duffy phenotyping can provide accurate results.
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.
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