Mahboubeh Ebrahimi

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

UNLABELLED 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, β-TrCP, is a novel regulator of p53. The current study aimed to assess the possible effects of TP53 IVS3 16 bp (rs17878362) and β-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 β-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 β-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 β-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.

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.

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.

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.