Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer.

Tumor protein 53 (TP53), a tumor suppressor gene, is a vital cellular cancer suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an oncoprotein that inhibits TP53 activity. A number of studies have examined the association of TP53 and MDM2 polymorphisms with the risk of common forms of cancer, but the findings remain inconclusive. The present study aimed to evaluate the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the MDM2 promoter region and the 16-bp I/D polymorphism (rs17878362) in TP53 on the susceptibility of prostate cancer (PCa) in a sample of the Iranian population. This case-control study included 103 patients with pathologically confirmed PCa and 142 patients with benign prostatic hyperplasia. The MDM2 40-bp I/D and TP53 16-bp I/D polymorphism was determined using polymerase chain reaction analysis. The results demonstrated that the MDM2 40-bp I/D polymorphism increased the risk of PCa in a co-dominant inheritance model [odds ratio (OR)=1.88; 95% confidence interval (CI)=1.11-3.19; P=0.023, D/D vs. I/I], while this variant marginally increased the risk of PCa in a dominant model (OR=1.69; 95% CI=1.00-2.83; P=0.051, I/D+D/D vs. I/I). No significant association was observed between the TP53 16-bp I/D polymorphism and PCa. In conclusion, the present study demonstrated that the 40-bp I/D polymorphism in the MDM2 promoter increased the risk of PCa in an Iranian population. Further investigations with diverse ethnicities and larger sample sizes are required to verify these results.

Association of TAP1 and TAP2 Gene Polymorphisms with Susceptibility to Pulmonary Tuberculosis.

TAP1 and TAP2 genes encode heterodimeric molecule involved in endogenous antigen processing. The present study was undertaken to find out the possible association between TAP1 and TAP2 polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Polymorphisms of TAP1 (rs1057141, rs1135216) and TAP2 (rs2228396, rs241447, rs67511411, rs141555015) were determined in 173 PTB patients and 164 healthy subjects. Our findings showed that rs1135216 AG, GG and AG+GG genotypes increased the risk of PTB in comparison with AA (OR=2.36, 95%CI=1.47-3.79, p<0.001; OR=19.13, 95%CI=2.47-148.2, p<0.001 and OR=2.77, 95%CI=1.74-4.39, p<0.001, respectively). The rs1135216 G allele was associated with increased risk of PTB (OR=2.65, 95%CI=1.784-3.969, p<0.001). TAP2 rs241447 AG and AG+GG genotypes decreased the risk of PTB (OR=0.41, 95%CI=0.26-0.65, p<0.001; OR=0.54, 95%CI=0.35-0.85, respectively). No significant association was found between TAP1 (rs1057141), TAP2 (rs2228396, rs67511411, rs141555015) variants and PTB. In conclusion, our findings proposed that TAP gene polymorphisms might be associated with PTB susceptibility among patients in Zahedan, southeast Iran.

The functional 4-bp insertion/deletion ATTG polymorphism in the promoter region of NF-KB1 reduces the risk of BC.

Nuclear factor kappaB (NF-kB) plays a key role in mammary gland development and breast cancer (BC) progression. A functional -94 insertion/deletion ATTG polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to affect NF-KB1 expression and confer susceptibility to different types of cancer. The current study aimed to assess the association of NFKB1 -94 insertion/deletion ATTG promoter polymorphism and BC risk in an Iranian population. A total of 439 subjects including on 236 BC patients and 203 healthy women were recruited. The NF-KB1 -94ins/del ATTG polymorphism was genotyped by Allele-Specific polymerase chain reaction (AS-PCR) method. Our results demonstrated that the NF-KB1 -94ins/del ATTG polymorphism was associated with a reduced risk of BC in Codominant (Ins/Ins vs. Del/Del: OR = 0.33, 95%CI = 0.17-0.64; P= 0.001), dominant (Ins/Ins vs. Ins/Del+Del/Del: OR = 0.64, 95%CI = 0.42-0.97; P= 0.027) and recessive (Ins/Del+Del/Del vs. Del/Del: OR = 0.40, 95%CI = 0.21-0.75; P= 0.002) tested inheritance models. Additionally, the Del allele of NF-KB1 -94ins/del ATTG variation with a higher prevalence in the control group compared to the BC patients (43.3% vs. 33.5%) was associated with a decreased risk of BC (OR = 0.66, 95%CI = 0.50-0.86, P= 0.003). In conclusion, our findings for the first time, suggest that the NF-KB1 -94ins/del Del allele and Del/Del genotype were associated with a reduced risk of BC which may contribute as protective factors against BC.

Association of DC-SIGN and DC-SIGNR Repeat Regions with Susceptibility to Pulmonary Tuberculosis in Zahedan, Southeastern Iran.

There are conflicting results concerning DC-SIGN and DC-SIGNR VNTR polymorphisms. The present study aimed to evaluate the possible association between DC-SIGN as well as DC-SIGNR VNTR polymorphisms and pulmonary tuberculosis (PTB) in a sample of Iranian population. This case-control study was done on 171 PTB and 161 healthy subjects. The variants were detected by polymerase chain reaction (PCR). DC-SIGNR VNTR genotypes in cases were 12.7% for 5/5, 2.4% for 6/5, 32.7% for 7/7, 38.2% for 7/5, 5.5% for 7/6, 1.2% for /5, 0.6% for 9/6, 6.7% for 9/7 in PTB patients and 19.7% for 5/5, 2.0% for 6/5, 31.6% for 7/7, 37.5% for 7/5, 5.7% for 7/6, 0.0% for 9/5, 0.7% for 9/6, 2.6% for 9/7 in controls. The findings showed no significant association between DC-SIGNR VNTR polymorphism and PTB. All subjects in cases and controls were 7/7 genotype regarding DC-SIGN VNTR polymorphism. Our data propose that DC-SIGNR VNTR, as well as DC-SIGN VNTR, were not associated with the risk of PTB in a sample of Iranian population.

Macrophage migration inhibitory factor -173 G/C polymorphism is associated with an increased risk of pulmonary tuberculosis in Zahedan, Southeast Iran.

Macrophage migration inhibitory factor (MIF) has an important role in controlling infection. The aim of this study was to evaluate the possible association between MIF -173 G/C functional polymorphism and pulmonary tuberculosis (PTB) in an Iranian population from Zahedan Southeast Iran. This case-control study was done on 161 PTB and 142 healthy subjects. Genomic DNA was extracted from all participants by salting out method. The MIF -173 G/C variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The finding showed that the MIF -173 G/C polymorphism increased the risk of PTB in codominant (OR=1.76, 95 % CI=1.05-2.95, p=0.038, GC vs GG) and dominant (OR=1.78, 95 % CI=1.09-2.91, p=0.027, GC+CC vs GG) tested inheritance models. Furthermore, the minor allele frequency (MAF) increased the risk of PTB in comparison with G allele (OR=1.63, 95 % CI=1.07-2.48, p=0.028). In conclusion, the present study provides evidence that -173 G/C polymorphism may increase the risk of PTB.

Effect of TP53 16-bp and ß-TrCP 9-bp INS/DEL polymorphisms in relation to risk of breast cancer.

P53 as a tumor suppressor and an apoptosis modulator, is the regulator of the cell cycle and apoptosis, and contributes to mammary gland development and breast cancer (BC) progression. BTRC gene (Homo sapiens beta-transducing repeat containing E3 ubiquitin protein ligase) encoded protein, ß-TrCP, is a novel regulator of p53. The current study aimed to assess the possible effects of TP53 IVS3 16 bp (rs17878362) and ß-TrCP 9 bp (rs16405) INS/DEL polymorphisms on BC risk in an Iranian population. A total of 439 women including 236 BC patients and 203 healthy women were recruited. The TP53 and ß-TrCP INS/DEL polymorphisms were genotyped by allele-specific polymerase chain reaction method. Our data demonstrated that the TP53 16-bp INS/DEL variation was associated with an increased risk of BC in codominant (INS/INS vs. DEL/DEL: OR=1.82; 95% CI=1.02-3.23; P=0.042) and dominant (Del/INS+INS/INS vs. DEL/DEL: OR=1.48; 95% CI=1.03-2.21; P=0.044) models. Additionally, the variant allele (INS) of TP53 DEL/INS polymorphism with a relatively higher frequency in cases than in controls (35.6 vs. 27.8) was a risk factor for BC (OR=1.43; 95% CI=1.06-1.93; P=0.017). With respect to ß-TrCP INS/DEL polymorphism, our study failed to find any difference in allele and genotype distribution between BC patients and controls in codominant, dominant and recessive tested inheritance models (P>0.05). Furthermore, no significant association among the ß-TrCP and TP53 genotype distribution and clinical characteristics of BC patients were found (P>0.05). Our findings suggest that the TP53 16-bp INS/INS and DEL/INS+INS/INS genotypes as well as the INS allele could be genetic factors related to BC risk.

Association between Programmed Cell Death 6 Interacting Protein Insertion/Deletion Polymorphism and the Risk of Breast Cancer in a Sample of Iranian Population.

It has been suggested that genetic factors contribute to patients' vulnerability to breast cancer (BC). The programmed cell death 6 interacting protein (PDCD6IP) encodes for a protein that is known to bind to the products of the PDCD6 gene, which is involved in the apoptosis pathway. The aim of this case-control study is to investigate the relationship between the PDCD6IP 15 bp insertion/deletion (I/D) polymorphism (rs28381975) and BC risk in an Iranian population. A total of 491 females, including 266 BC patients and 225 control subjects without cancer, were enrolled into the study. Our findings revealed that the PDCD6IP 15 bp I/D polymorphism decreased the risk of BC in codominant (OR = 0.44, 95% CI = 0.31-0.65, p < 0.0001, I/D versus DD; OR = 0.39, 95% CI = 0.17-0.88, p = 0.030, I/I versus DD) and dominant (OR = 0.44, 95% CI = 0.30-0.63, p < 0.0001, D/I + I/I versus D/D) tested inheritance models. Also, the PDCD6IP I allele significantly decreased the risk of BC (OR = 0.59, 95% CI = 0.45-0.78, p < 0.001) compared to the D allele.

Lack of Association between miRNA-146a rs2910164 and miRNA-499 rs3746444 Gene Polymorphisms and Susceptibility to Pulmonary Tuberculosis.

Single-nucleotide polymorphisms (SNPs) in miRNAsmay alter its expression levels or processing and contribute to susceptibility to a wide range of diseases. Our study aimed to evaluate the possible association between miRNA-146a rs2910164 and miRNA-499 rs3746444 polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in a sample of Iranian population. This case- control study was performed on 202 PTB patients and 204 healthy individuals. Genotyping was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). The results indicated that neither miRNA-499 rs3746444 nor miRNA-146a rs2910164 are associated with the risk of PTB in a sample of Iranian population. Larger studies with different ethnicities are required to validate our findings.

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

Macrophages and T-lymphocytes are involved in immune response to Mycobacterium tuberculosis. Macrophage produces interleukin (IL)-1 as an inflammatory mediator. IL-1 receptor antagonist (IL1-Ra) is a natural antagonist of IL-1 receptors. In this study we aimed to examine the possible association between the variable number of tandem repeats (VNTR) of the IL-1 receptor antagonist (IL1RN) gene and pulmonary tuberculosis (TB) in a sample of Iranian population. Our study is a case-control study and we examined the VNTR of the IL1RN gene in 265 PTB and 250 healthy subjects by PCR. Neither the overall chi-square comparison of PTB and control subjects nor the logistic regression analysis indicated any association between VNTR IL1RN polymorphism and PTB. Our data suggest that VNTR IL1RN polymorphism may not be associated with the risk of PTB in a sample of Iranian population. Larger studies with different ethnicities are needed to find out the impact of IL1RN VNTR polymorphism on risk of developing TB.

Association between CCNE1 polymorphisms and the risk of breast cancer in a sample of southeast Iranian population.

Cyclin E1 (CCNE1) is a key proto-oncogene. The present study aimed to investigate the effects of single nucleotide polymorphisms in CCNE1 on the risk of breast cancer (BC) in an Iranian population in southeast of Iran. A total of 491 subjects including 266 BC patients and 225 healthy control women were participated in the study. Genotyping of CCNE1 rs3218073 and 72010703 polymorphisms was done using allele-specific polymerase chain reaction (AS-PCR) and rs1406 by PCR-RFLP method.Our findings showed that rs1406 C/A polymorphism increased the risk of BC in codominant (OR 1.60, 95% CI 1.05-2.43, p=0.032 CA vs CC; OR 2.35, 95% CI 1.23-4.49, p=0.011 AA vs CC) and dominant (OR 1.69, 95% CI 1.22-2.56, p=0.012 CA+AA vs CC) inheritance models. The rs1406 A allele increased the risk of BC (OR 1.37, 95% CI 1.06-1.76, p=0.019) in comparison with C allele. On the other hand, CCNE1 rs72010703 (4-bp I/D) and rs3218073 polymorphisms did not show any significant association with BC. This study indicates that CCNE1 rs1406 polymorphism may contribute to BC risk.

Association between hTERT polymorphisms and the risk of breast cancer in a sample of Southeast Iranian population.

BACKGROUND: Breast cancer (BC) is considered to be one of the most important causes of death worldwide, and it affects the Iranian female population a decade earlier than female in other parts of the world. Human telomerase reverse transcriptase (hTERT) is a main subunit of the telomerase complex. MNS16A is located downstream of the hTERT gene and is recognized as the regulator of hTERT promoter activity. The aim of the present study was to access the possible impact of hTERT variants on BC risk in an Iranian population in southeast Iran. METHODS: A total of 491 subjects including 266 BC patients and 225 healthy women participated in the study. Polymerase chain reaction (PCR) was used to genotype the MNS16A variable number of tandem repeats and 177 bp ins/del polymorphisms in the hTERT gene. PCR-RFLP and ARMS-PCR were used to genotype hTERT rs2736098 and 2735940, respectively. The association between genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CI) from logistic regression analyses. A p-value of <0.05 was considered statistically significant. RESULTS: The MNS16A genotype frequency distribution in BC patients was: LL, 43.2%; LS, 51.1%; and SS, 5.7%, and in controls: LL, 29.5%; LS, 68.3%; and SS, 2.2%. The LS genotype decreased the risk of BC compared with LL (OR=0.51, 95% CI=0.35-0.75, p<0.001). The hTERT 177 bp ins/del polymorphism was not polymorphic in our population. All subjects had the ins/ins genotype. Our findings indicate that the MNS16A genotype and hTERT rs2736098 variant were associated with BC risk in the study. We also showed that the rs2736098 A/G polymorphism increased the risk of BC (OR=1.80, 95% CI=1.12-2.88, p=0.017, AG vs AA; OR=1.80, 95% CI=1.06-3.06, p=0.033, GG vs AA; OR=1.87, 95% CI=1.19-2.94, p=0.006, AG+GG vs AA). No significant association was found between the rs2735940 C/T variant and BC. CONCLUSION: Our findings indicate that the MNS16A genotype and the hTERT rs2736098 variant influence the risk of BC in an Iranian population in southeast Iran.

Evaluation of CCL5 -403 G>A and CCR5 Δ32 gene polymorphisms in patients with breast cancer.

BACKGROUND: Recent evidence has demonstrated the implication of CC chemokine ligand 5 (CCL5) and CC chemokine receptor 5 (CCR5) in breast tumor initiation and progression. OBJECTIVE: The purpose of this study was to investigate whether single nucleotide polymorphisms of CCL5 -403 G>A (rs2107538) and CCR5 Δ32 genes are associated with the breast cancer (BC) risk. METHODS: A total of 439 subjects including on 236 BC patients and 203 healthy controls from the same area were recruited. The CCL5 -403 G>A and CCR5 Δ32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR) and PCR, respectively. RESULTS: Our data demonstrated that the CCL5 -403 GA and GA+AA genotypes, with a higher frequency in the BC patients compared to the control group, were associated with an increased risk of BC in the codominant (GG vs. GA OR=1.75, 95%CI=1.07-2.86, P=0.025) and dominant models (GG vs. GA+AA: OR=1.84, 95%CI=1.15-2.93, P=0.014), respectively. Additionally, the A allele of CCL5 -403 G>A variation was found more prevalent in the BC patients than in controls (14% vs. 8%) and was a risk factor for BC (G vs. A: OR=1.87, 95% CI=1.21-2.89, P=0.004). CONCLUSIONS: Our findings highlighted that the CCL5 -403 G>A polymorphism is a risk factor for BC in our population. Our findings suggest that the CCL5 -403 GA and GA+AA genotypes and the A allele were associated with an elevated risk of BC which may function as risk factor for breast carcinoma.

Evaluation of rs3102735 and rs2073617 Osteoprotegerin Gene Polymorphisms and the Risk of Childhood Acute lymphoblastic Leukemia in Zahedan Southeast Iran.

INTRODUCTION: Osteoprotegerin (OPG), a soluble decoy receptor secreted by osteoblasts, binds RANK-L, preventing stimulation of osteoclastogenesis. In the present study we aimed to investigate the impact of OPG variants and susceptibility to childhood acute lymphocytic leukemia (ALL) in a sample of Iranian population. METHODS: This case-control study was done on 98 ALL and 124 healthy children. We genotyped the polymorphisms using tetra-primer ARMS-PCR (T-ARMS-PCR). RESULTS: Our findings showed that neither rs3102735 nor rs2073617 variants were associated with ALL in a sample of Iranian population. Concerning rs3102735 polymorphism, the age of ALL predispositions was significantly higher in TC+CC genotype than TT genotype (P=0.032). Furthermore, the CSF involvement was significantly higher in ALL subjects carrying TC+CC genotype (p=0.044). CONCLUSION: We found no association between OPG (rs3102735, rs2073617) gene polymorphisms and risk of childhood ALL. Further studies with larger sample sizes and various ethnicities are necessary to verify our findings.