Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

INTRODUCTION: Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. AIMS: We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. METHODS: We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. RESULTS: In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. CONCLUSIONS: These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-ß, IL-1R1 and IL-R antagonists might be involved in the GT progression.

Association of LIN28B Gene Polymorphisms (rs221634, rs221635, rs314276, rs9404590, and rs12194974) with Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND AND AIM: Lymphoma is a common hematopoietic cancer.  It has been proposed that LIN28B gene and its variations may have function in cancer progression and metastasis. Therefore, the purpose of this investigation has been to examine the correlation among LIN28B gene polymorphisms (such as rs221634 A>T, rs221635 T> C, rs314276 C>A, rs9404590 T>G, and rs12194974 G>A) as well as the risk of NHL in an Iranian sample. MATERIALS AND METHODS: In the current case-control research, 175 individuals with Non-Hodgkin Lymphoma along with 175 normal controls participated; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology has been utilized to the genotype samples. RESULTS: Our data demonstrated that rs12194974 and the rs221635 variants have been correlated with higher NHL risk, while rs221634 and rs314276 variants were correlated with lower risk of NHL (P≤0.05). In addition, we detected an association between rs221634 and treatment with R-CHOP. No substantial correlation has discovered among rs9404590 polymorphism and NHL in any inheritance models (P≥0.05). CONCLUSION: This was the first investigation evaluating the correlation among LIN28B gene polymorphisms as well as the occurrence of NLH. Further studies in different ethnic populations and large-scale sample size are needed to support results.

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case-Control Study with Bioinformatics Analysis.

Breast cancer (BC) is a complex disease caused by molecular events that disrupt cellular survival and death. Discovering novel biomarkers is still required to better understand and treat BC. The reticulon-4 (RTN4) gene, encoding Nogo proteins, plays a critical role in apoptosis and cancer development, with genetic variations affecting its function. We investigated the rs34917480 in RTN4 and its association with BC risk in an Iranian population sample. We also predicted the rs34917480 effect on RTN4 mRNA structure and explored the RTN4's protein-protein interaction network (PPIN) and related pathways. In this case-control study, 437 women (212 BC and 225 healthy) were recruited. The rs34917480 was genotyped using AS-PCR, mRNA secondary structure was predicted with RNAfold, and PPIN was constructed using the STRING database. Our findings revealed that this variant was associated with a decreased risk of BC in heterozygous (p = 0.012), dominant (p = 0.015), over-dominant (p = 0.017), and allelic (p = 0.035) models. Our prediction model showed that this variant could modify RTN4's mRNA thermodynamics and potentially its translation. RTN4's PPIN also revealed a strong association with apoptosis regulation and key signaling pathways highly implicated in BC. Consequently, our findings, for the first time, demonstrate that rs34917480 could be a protective factor against BC in our cohort, probably via preceding mechanisms.

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.

BACKGROUND: Caspases (CASPs) are the main executors of the apoptotic process. Studies to date have shown the role of caspase-8 (CASP8) and caspase-9 (CASP9) in carcinogenesis. Therefore, the aim of this study was to investigate the associations between CASP9-rs4233532, CASP9-rs4646018, and CASP8- rs1045485 gene polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility in an Iranian population-based study. Moreover, it was examined whether such the genotype of these polymorphisms is related with clinicopathological characteristics of NHL. METHODS: 175 patients with NHL and 175 age- and sex-matched controls were enrolled in this study. We determined the genotypes of single nucleotide polymorphisms (SNPs) from CASP genes with Tetra ARMS-PCR (Amplification refractory mutation system) method. RESULTS: Statistically significant association were observed between CASP9-rs4646018 and increased risk of NHL under codominant CC, codominant TC, and dominant TC+CC genetic models. Our results showed that the A allele of CASP8-rs1045485 was a protective factor for NHL and GArs1045485 genotype significantly reduced risk of NHL. In contrast, CASP9- rs4233532 was not linked to NHL susceptibility. No relationship was detected between CASP8-rs1045485 and CASP9-rs4233532 and NHL clinicopathological characteristics, however genetic variation in CASP9-rs4646018 was associated with histology, treatment and radio therapy of NHL. CONCLUSIONS: Our study presented that the CASP8- rs1045485 and CASP9-rs4646018 polymorphisms could affect the risk of NHL in Iranian populations which was the first report to show the significant relationship between rs1045485, rs4646018 polymorphisms and NHL susceptibility. Replication large-scale case-control studies in different ethnicities are warranted to verify these findings.

Association between PAX8AS1 (rs4848320 C > T, rs1110839 G > T, and rs6726151 T > G) and MEG3 (rs7158663) gene polymorphisms and non-Hodgkin lymphoma risk.

Long non-coding RNA (lncRNA) PAX8 antisense RNA 1 (PAX8AS1) and Maternal-expressed gene 3 (MEG3) contribute to the pathogenesis of various malignancies including non-Hodgkin lymphoma (NHL). In this study, we aimed to examine the possible association of polymorphisms of PAX8 and MEG3 and the risk NHL. A total of 175 patients and 175 healthy subjects were genotyped by PCR-RFLP and Tetra-Arms PCR assays. Results demonstrated rs4848320 C > T and rs6726151 T > G of PAX8AS1 and rs7158663 of MEG3 play a potential role in the susceptibility of NHL and PAX8AS1 rs1110839 T > G variant was associated with decreased risk of NHL. Haplotype analysis of rs1110839, rs4848320, and rs6726151 demonstrated GCG haplotype is associated with increased risk of lymphoma and TTG, TTT, and GTT haplotypes are related to decreased lymphoma susceptibility.

Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families.

BACKGROUND: Intellectual disability (ID) is a heterogeneous group of neurodevelopmental disorders that is characterized by significant impairment in intellectual and adaptive functioning with onset during the developmental period. Whole-exome sequencing (WES)-based studies in the consanguineous families with individuals affected with ID have shown a high burden of relevant variants. So far, over 700 genes have been reported in syndromic and non-syndromic ID. However, genetic causes in more than 50% of ID patients still remain unclear. METHODS: Whole-exome sequencing was applied for investigation of various variants of ID, then Sanger sequencing and in silico analysis in ten patients from five Iranian consanguineous families diagnosed with autosomal recessive neurodevelopmental disorders, intellectual disability, performed for confirming the causative mutation within the probands. The most patients presented moderate-to-severe intellectual disability, developmental delay, seizure, speech problem, high level of lactate, and onset before 10 years. RESULTS: Filtering the data identified by WES, two novel homozygous missense variants in FBXO31 and TIMM50 genes and one previously reported mutation in the CEP290 gene in the probands were found. Sanger sequencing confirmed the homozygote variant's presence of TIMM50 and FBXO31 genes in six patients and two affected siblings in their respective families. Our computational results predicted that the variants are located in the conserved regions across different species and have the impacts on the protein stability. CONCLUSION: Hence, we provide evidence for the pathogenicity of two novel variants in the patients which will expand our knowledge about potential mutation involved in the heterogeneous disease.

Association between the Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Lymphoma.

Introduction: Lymphoma is a common hematopoietic cancer. Immunosuppression is one of the main risk factors for the development of lymphoma. The interleukin (IL)-1 receptor antagonist IL1RN, which binds to the IL-1 receptor, moderates a variety of immune responses related to IL-1. We aimed to assess the impact of IL1RN variable number of tandem repeats (VNTR) polymorphism on lymphoma risk in an Iranian population sample. Materials and Methods: DNA was extracted from peripheral blood of 120 subjects with non-Hodgkin Lymphoma (NHL), 50 subjects with Hodgkin's lymphoma (HL), and 186 unrelated healthy individuals. IL1RN VNTR polymorphism was detected using polymerase chain reaction. Results: Our findings revealed that the IL1RN VNTR polymorphism was associated with protection against NHL (P≤0.001, OR: 0.30, 95% CI: 0.18-0.53). The IL1RN 2 allele significantly decreased the risk of NHL (p = 0.023, OR = 0.66, 95%CI = 0.46-0.93). In addition, we found that IL1RN 1/2 was associated with a lower risk of HL (p ≤0.001, OR = 0.24, 95%CI = 0.12-0.50). Conclusion: Our results suggest that the presence of IL1RN VNTR polymorphism is associated with a decreased risk of lymphoma in an Iranian subpopulation in southeast Iran.

Association between HOTAIR Polymorphisms and Lymphoma.

INTRODUCTION: The long non-coding RNA, HOTAIR, involved in cancer initiation and development. OBJECTIVE: The aim of present study was to investigate the association of single nucleotide polymorphisms in the HOTAIR gene with lymphoma. METHODS: We conducted a case-control study of 156 individuals with non-Hodgkin Lymphoma (NHL), 53 individuals with Hodgkin's lymphoma (HL), and 245 unrelated healthy individuals to identify the genotype frequencies of each polymorphism. Genotyping of the SNPs (rs920778 T>C, rs1899663 G>T, rs4759314 A>G and rs12826786 C>T) was carried out using the polymerase chain reaction-restriction fragment length polymorphism. RESULTS AND CONCLUSION: The finding showed that rs1899663 variant of HOTAIR gene significantly decreased the risk of NHL in codominant, dominant, over-dominant and allelic inheritance models. We did not find any association between HOTAIR rs12826786, rs920788 and rs4759314 variants and NHL. The results indicated that neither the overall chi-square comparison of the cases and controls, nor the logistic regression analysis showed any association between HOTAIR polymorphisms and HL. Conclusively, our findings showed that rs1899663 of HOTAIR significantly decreased the risk of non-Hodgkin Lymphoma.

Association Between miR-146a rs2910164 Polymorphism and Breast Cancer Susceptibility: An Updated Meta-Analysis of 9545 Cases and 10030 Controls.

BACKGROUND: Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC. METHODS: Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC. RESULTS: Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility. CONCLUSION: In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.

Association between the IL-1A, IL-1B and IL-1R polymorphisms and lymphoma.

We investigate the impact of IL-1A, IL-1B and IL-1R1 polymorphism on lymphoma. This study consisted of 155 Non-Hodgkin's lymphoma (NHL) patients 55 Hodgkin's lymphoma (HL) patients and 150 healthy individuals. PCR-RFLP method and ARMS PCR were used for genotyping of IL-1A rs3783553, IL-1B rs3917356, rs16944, IL-1R1 rs10490571 and IL-1A rs3783550 polymorphism. The results showed that the CC genotype of rs3783550 as well Ins/del of rs3783553 increased the risk of NHL. In contrast the AG genotype of rs3917356 and AG also AG + AA genotype of rs10490571 decreased the risk of NHL. The result revealed that the CC genotype of rs3783550 and AG genotype of rs3917356 increased risk of HL.

Lack of Association Between TNF-alpha rs1800629 (-308G > A) Polymorphism and Nephrotic Syndrome.

INTRODUCTION: Idiopathic Nephrotic Syndrome is a multifactorial disease that accompanying with immune system dysfunction. Cytokines as potent immunomodulators have a key role in pathogenesis of the disease. We aimed to evaluate the association between TNFα -308G > A polymorphism with Idiopathic Nephrotic Syndrome and its effect on the response to steroid therapy. METHODS: This case-control study was performed on 168 patients with Nephrotic Syndrome and 153 healthy children. Genotyping of TNF-α rs1800629 (-308G > A) variant was detected by polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). RESULTS: The results revealed that there was no significant difference in allele (P > .05, OR = 0.92, 95% CI: 0.59 to 1.43) or genotype (P > .05, OR = 1.00; 95% CI: 0.62 to 1.65) frequency of TNF-α rs1800629 (-308G > A) between childhood cases of nephrotic syndrome and healthy controls. Also no association was found between genotype (P > .05, OR = 2.28; 95% CI: 1.03 to 5.04), and allele frequency (P > .05, OR = 1.93; 95% CI: 0.97 to 3.87) among the SSNS and SRNS groups. CONCLUSION: Our results did not support any association between the TNF polymorphism and the risk of nephrotic syndrome in a sample of southeast Iranian population.

Association between Genetic Polymorphisms of miR-1307, miR- 1269, miR-3117 and Breast Cancer Risk in a Sample of South East Iranian Women.

INTRODUCTION: MicroRNAs (miRNAs) play an essential role in the susceptibility and development of cancer cells. OBJECTIVE: Examining the dependency of breast cancer risk with genetic polymorphisms of miR-1307, miR-1269, and miR-3117 in a sample of Iranian women (southeast region). METHODS: The case-control study consisted of 520 individuals (260 diagnosed BC patients, 260 healthy individuals). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping of miR-1307 rs7911488, miR-1269 rs73239138, and miR-3117 (rs4655646 and rs7512692) polymorphisms. RESULTS AND CONCLUSION: This study provided evidence that miR-1307 rs7911488 polymorphism significantly reduced the risk of BC in heterozygous AG genotype, as well as dominant (AG+GG) genotype and G allele. A significant correlation was found between dominant (AA+AG) genotype, the A allele and protection against BC due to miR-1269 rs73239138 in the sample of study. In contrast, our findings suggested that AG genotype and G allele of miR-3117 rs4655646 polymorphism could increase BC's susceptibility among the southeastern Iranian females. The miR-3117 rs7512692 variant also increased the risk of BC in codominant, dominant and recessive models, as well as the T allele. The possible dependency of miR-1307, miR-1269, and miR-3117 variants with patients' clinicopathological characteristics and BC was also studied. It was concluded that there is a correlation between miR-3117 rs7512692 variant and tumor grade (p=0.031); also, a correlation between miR-1269 rs73239138 variant and progesterone receptor status (p=0.006). The current investigation revealed that miR-1307, miR-1269, and miR-3117 polymorphisms might play a crucial role in the Iranian population's vulnerability to BC.
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Evaluating the Possible Association between PD-1 (Rs11568821, Rs2227981, Rs2227982) and PD-L1 (Rs4143815, Rs2890658) Polymorphisms and Susceptibility to Breast Cancer in a Sample of Southeast Iranian Women.

INTRODUCTION: Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) play a critical role as a  regulator of immune-system cells, including T cell, natural killer T (NKT), monocytes, dendritic cells (DC), and B cells. OBJECTIVE: This study aimed to find a possible association between PD-1 (rs11568821, rs2227981, rs2227982), and PD-L1 (rs4143815, rs2890658) variants and Breast Cancer (BC) risk in a sample of southeast Iranian women. METHOD: The case-control study consisted of 520 individuals, including 260 histologically confirmed BC patients and 260 non-cancer age-matching healthy women as the control group. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) methods were used for genotyping of PD-1 (rs11568821, rs2227981, rs2227982), and PD-L1 (rs4143815, rs2890658) polymorphisms. RESULTS AND CONCLUSION: Our findings indicated that the PD-L1 rs4143815 (G/C) variant meaningfully reduced the risk of BC. However, the PD-L1 rs2890658 variant increased the BC risk in the AC genotype as well as the A allele. Furthermore, we could not find a meaningful association between PD-1 rs11568821, PD-1 rs2227981, PD-1 rs2227982, and BC. Our team examined the possible association between variants and clinicopathological characteristics, including age, size of tumour, lymph node, histology, grade of tumour, estrogen and progesterone receptors status as well as human growth factor receptor 2 (HER2). Our findings demonstrated that PD-L1 rs4143815, PD-L1 rs2890658, PD-1 rs2227982 had a significant association with age. Additionally, we found a significant relation between PD-1 rs2227982 variant and tumour size. Statistical analyzes of PD-1 rs2227981 and PD-1 rs11568821 variants showed a meaningful relation between tumour grade and tumour stage (p=0.006), respectively.
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Association of APOBEC3 deletion with cancer risk: A meta-analysis of 26 225 cases and 37 201 controls.

Previous studies have found inconsistent results regarding gene deletion in APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) and risk of cancer. We conducted a meta-analysis of all eligible case-control studies to find out the associations between APOBEC3 deletion and cancer risk by pooling the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Overall, the findings from 20 studies (13 articles) involving of a total of 26 225 cases and 37 201 controls revealed that DD genotype was associated significantly with increased cancer risk compared to II genotype (OR = 1.25, 95% CI = 1.01-1.56, P = 0.04). Stratified analysis from 10 studies including 14 757 cases and 17 930 controls revealed that I/D variant significantly increased the risk of breast cancer in heterozygous codominant (OR = 1.15, 95% CI = 1.03-1.28, P = 0.02, ID vs II), dominant (OR = 1.15, 95% CI = 1.01-1.31, P = 0.03, ID + DD vs II), overdominant (OR = 1.11, 95% CI = 1.05-1.25, P < 0.0001, ID vs DD + II) and allele (OR = 1.15, 95% CI = 1.13-1.25, P = 0.03, D vs I) inheritance models. In conclusion, the data propose that APOBEC3 deletion is significantly associated with increased susceptibility to cancer in overall and breast cancer. Our findings require well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities.

Expression of LRP Gene in Breast Cancer Patients Correlated with MRP1 as Two Independent Predictive Biomarkers in Breast Cancer

Background: Breast cancer is the most common malignancy in women. Multidrug resistance (MDR) is still a great obstacle of breast cancer chemotherapy. We have previously shown that multidrug resistance-associated protein 1 (MRP1) is associated with response to neoadjuvant chemotherapy. The lung resistance-related protein (LRP) is identified as a prognostic marker and response to treatment factor which has been studied mainly in hematological malignancy and leukemia. In this study, we aimed to analyze LRP expression and possible correlation between the expression level of this gene with MRP1 as a candidate marker for chemotherapy resistance. Materials and Methods: We collected 54 breast tumors and adjacent normal tissues from Iranian breast cancer patients and Real time RT-PCR was employed to measure the gene expression level in our samples. Results: MRP1 and LRP expression level were significantly lower in tumor tissues of the patients responding to chemotherapy compared to non-responding patients. No relation between the expression level of either of these genes and clinicopathology markers was found. Conclusion: Our results suggest that LRP gene expression is correlated to MRP1 in human breast cancer cells and may affect the clinical response to treatment.

Association between miR-218 rs11134527 polymorphism and risk of selected types of cancer in Asian population: An updated meta-analysis of case-control studies.

Several studies inspected the relationship between miR-218 rs11134527 polymorphism and the risk of some human cancers, but the findings remains controversial. We designed an update meta-analysis aiming to validate the association between rs11134527 polymorphism of miR-218 and cancer risk. Eligible studies including 7989 cancer cases and 8761 controls were recognized by searching Web of Science, PubMed, Scopus, and Google scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between rs11134527 variant and cancer risk. The overall results indicated no significant relationship between miR-218 rs11134527 polymorphism and cancer risk in codominant, dominant, recessive, overdominant, and allele inheritance model tested. Stratified analysis showed that rs11134527 variant significantly increased the risk of developing esophageal squamous cell carcinoma (ESCC) in heterozygous codominant (OR = 1.32, 95%CI = 1.03-1.69, p = 0.03, AG vs GG) inheritance model. In summary, the findings of this meta-analysis did not support an association between miR-218 rs11134527 polymorphism and cancer risk. Stratified analysis showed that rs11134527 variant significantly increased the risk of developing ESCC. Larger and well-designed researches are needed to estimate this association in detail.

Leukocyte Telomere Length Shortening, hTERT Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia

Background: Telomeres are involved in chromosomal stability, cellular immortality and tumorigenesis. Human telomerase reverse transcriptase (TERT) is essential for the maintenance of telomere DNA length. Recently, a variable tandem-repeats polymorphism, MNS16A, located in the downstream region of the TERT gene, was reported to have an effect on TERT expression and telomerase activity. Previous studies have linked both relative telomere length (RTL) and TERT variants with cancer. Therefore, we evaluated associations between RTL, TERT gene polymorphisms (hTERT, rs2735940 C/T and MNS16A Ins/Del) and risk of childhood acute lymphoblastic leukemia (ALL) in an Iranian population. Methods: RTL was determined by a multiplex quantitative PCR-based method, and variants of the hTERT, rs2735940 C/T and MNS16A Ins/Del, were genotyped by amplification refractory mutation system PCR (ARMS-PCR), and PCR, respectively. Results: Our results indicated that RTL was shorter in ALL patients (1.53±0.12) compared to the control group (2.04±0.19) (P=0.029). However, no associations between hTERT gene variants or haplotypes and the risk of childhood ALL were observed (P>0.05). Also hTERT polymorphisms were not associated with RTL or patient clinicopathological characteristics, including age (P=0.304), sex (P=0.061) organomegally (P=0.212) CSF involvement (P=0.966) or response to treatment (P=0.58). Conclusions: We found that telomere attrition may be related to the pathogenesis of childhood ALL, irrespective to TERT variants.

Evaluation of 4-bp insertion/deletion polymorphism within the 3'UTR of SGSM3 in bladder cancer using mismatch PCR-RFLP method: A preliminary report.

The small G protein signaling modulator 3 (SGSM3) has been shown to be associated with small G-protein-coupled receptor signaling. There is little data regarding the impact of SGSM3 polymorphisms on cancer risk. In the present study, we aimed to evaluate the impact of 4-bp insertion/deletion (rs56228771) polymorphism in the 3'UTR of SGSM3 and susceptibility to bladder cancer in a sample of the Iranian population. This case-control study included 143 pathologically confirmed bladder cancer patients and 144 healthy subjects. The SGSM3 4-bp ins/del (rs56228771) variant was determined by mismatch PCR-RFLP. The findings showed that ins/del genotype and ins allele of SGSM3 4-bp ins/del polymorphism significantly increased the risk of bladder cancer (OR = 3.11, 95%CI = 1.70-5.71, P < 0.0001 and OR = 2.11, 95%CI = 1.27-3.52, P = 0.004, respectively). Our findings support an association between 4-bp ins/del polymorphism in the 3'UTR of SGSM3 and the risk of bladder cancer in an Iranian population. Additional studies with larger sample sizes and diverse ethnicities are warranted to establish if such an association exists in general.

Long non-coding RNA PAX8-AS1 polymorphisms increase the risk of childhood acute lymphoblastic leukemia.

The present case-control study was conducted on 110 children with acute lymphoblastic leukemia (ALL) and 120 healthy children to determine the impact of polymorphisms in paired-box gene 8 (PAX8) antisense RNA 1 (PAX8-AS1), namely rs4848320 C>T, rs6726151 T>G and rs1110839 G>T, on ALL risk. Genotyping was performed through the polymerase chain reaction-restriction fragment length polymorphism method. The findings indicated that the rs4848320 variant increased the risk of ALL in codominant [CT vs. CC: odds ratio (OR)=2.13, 95% confidence interval (CI)=1.16-3.90, P=0.014; and TT vs. CC: OR=2.21, 95% CI=1.03-4.74, P=0.041], dominant (CT+TT vs. CC: OR=2.15, 95% CI=1.22-3.81, P=0.009,) and allele (T vs. C: OR=1.55, 95% CI=1.07-2.25, P=0.024) inheritance models. The rs6726151 variant significantly increased the risk of ALL in codominant (GT vs. GG: OR=1.88, 95% CI=1.08-3.27, P=0.036) and overdominant (GT vs. GG+TT: OR=2.08, 95% CI=1.23-3.53, P=0.008) inheritance models. No significant relationship was identified between the rs1110839 G>T variant and disease risk/protection in childhood ALL. In conclusion, the findings of the present study indicated that rs4848320 and rs6726151 polymorphisms of PAX8-AS1 may be a risk factor for the development of childhood ALL. Further studies with larger sample sizes and different ethnicities are now required to confirm these findings.