Cytokine rs361525, rs1800750, rs1800629, rs1800896, rs1800872, rs1800795, rs1800470, and rs2430561 SNPs in relation with prognostic factors in acute myeloid leukemia

Abstract

Background Cytokines were correlated with survival and disease progression in acute myeloid leukemia (AML). We aimed to evaluate the multivariate effect of TNF‐α rs361525, rs1800750, rs1800629, IL‐10 rs1800896, rs1800872, IL‐6 rs1800795, TGF‐β1 rs1800470, IFN‐γ rs2430561 single nucleotide polymorphisms (SNPs) on AML risk, the multivariate effect of SNPs on overall survival (OS) in AML and the association between the investigated SNPs and prognostic factors in AML. Methods All SNPs were genotyped in 226 adult AML cases and 406 healthy individuals. AML patients were investigated for FLT3 (ITD, D835), DNMT3A (R882), and NPM1 type A mutations. Results Univariate analysis revealed that age above 65 years had a negative influence on survival (P < .001). The presence of the rs1800750 variant genotype (P = .005) or FLT3‐ITD mutation (P = .009) in a cytogenetic high‐risk group (P = .003) negatively influenced OS. A negative association was observed between Eastern Cooperative Oncologic Group Scale status > 2, lactate dehydrogenase (LDH) level, platelet (PLT) count <40 000 cells/mm3, and OS. Multivariate Cox regression analysis showed that the presence of the rs1800750 variant genotype was a risk factor for death (P = .007), and that blast percentage, LDH level (≥600 IU/L), and cytogenetic high‐risk were independent significant predictors for death in AML (P = .04, corrected HR = 1.20; P = .022, corrected HR = 1.24; P = .021, corrected HR = 1.34, respectively). Conclusions Age above 65 years, PLT count, TNF‐α rs1800750 variant genotype, blast percentage, LDH level, and cytogenetic high‐risk may be used as independent risk factors to assess AML mortality.

Modelling the Effects of MCM7 Variants, Somatic Mutations, and Clinical Features on Acute Myeloid Leukemia Susceptibility and Prognosis

“…Our findings suggest that LDH level ≥600 IU/L could be a useful biomarker for OS. Our observation is in line with the data reported by our group in a previous study [30], as well as with studies reported by Walaa et al [13] and Hu et al [14].…”

“…The investigated MCM7 SNPs had no significant effect on OS in either univariable Cox regression analysis or multivariable regression analysis. There were significant associations between OS of AML patients and age at diagnosis > 65 years (p < 0.001), WBC count ≥ 10,000 cells/mm 3 (p = 0.025), LDH ≥ 600IU/L (p = 0.003), ECOG performance status grade ≥2 at diagnosis (p < 0.001), ELN highand intermediate-risk (p < 0.001), and presence of FLT3 ITD mutation (p < 0.001), as we previously reported [30,31]. In addition, we observed an association between lower OS and combined FLT3 ITD/D835 (p = 0.027) and FLT3/DNMT3A (p = 0.039) mutations.…”

Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification

“…Our results regarding the differences in the OS according to the clinical and biological features (WBC and PLT counts, hemoglobin and LDH levels, blast percentage) were in line with a recent study that showed a negative association between the OS and the ECOG grade of 2 or higher, PLT count lower than 40 000 cells/mm 3 , and LDH levels at diagnosis of 600 IU/l or higher. 32 Our findings revealed an association between the ELN risk category and OS (P = 0.02): patients in the high -risk category had the shortest median OS (4 months), followed by those with the intermediate -risk category (7 months) and the low -risk category (12 months).…”

“…Bănescu et al 32 also showed that the age of 65 years or older had a negative influence on the OS. 32 Our analysis of the unadjusted prognostic impact of clinical factors on survival revealed a significantly shorter OS in patients older than 65 years, with high LDH levels at diagnosis (≥600 IU/l), and with the FLT3 ITD mutation. An association between the FLT3 mutation in patients with AML and shorter survival (P <0.001) was previously reported in a smaller group of patients.…”

Genetic polymorphisms in the Interleukins IL1B, IL4, and IL6 are associated with concomitant periodontitis and type 2 diabetes mellitus in Brazilian patients

“…18 In addition, the rs1800795 SNP was already associated with T2DM, 73,74 besides obesity 75 and lots of types of cancer. 76,77 Here, our analysis of the rs1800795 SNP (IL6 gene) showed no significant results for the susceptibility to periodontitis, but when focusing the association of both T2DM and periodontitis, we found that the men with CC genotype were 88% less prone to develop P + T2DM, with a true effect on the population between 98% and 30% (adjusted OR = 0.12, 95% CI = 0.02-0.70, P = .01).…”