Breast Cancer In Iranian Population Research Articles

A Combined Nomogram Model to Preoperatively Predict Positive Sentinel Lymph Biopsy for Breast Cancer In Iranian Population.

Axillary dissection in breast cancer provides useful information on the degree of axillary nodule involvement, which serves as a reliable indicator for the prognosis and staging of breast cancer in patients. The aim of this study was to develop and validate the nomogram model by combining prognostic factors and clinical features to predict the node status of preoperative breast guard positive node cancer. Subjects consisted of patients referring to hospitals with the diagnosis of breast cancer. Patients were allowed to substitute molecular subtypes with data on breast cancer diagnosis and prognosis as well as sentinel node status. The bootstrap review was used for internal validation. The predicted performance was evaluated based on the area under the receiver operating characteristic curve. According to the logistic regression analysis, the nomograms reported material strength between predictors and final status reliability. 1172 patients participated in the study, of whom only 539 patients had axillary lymph node involvement. The subtype, family history, calcification, and necrosis were not significantly related to axillary lymph node involvement. Tumor size, histological type, and lymphovascular invasion in multivariate logistic regression were significantly and directly correlated with axillary lymph node involvement. Nomograms, depending on the population, help make decisions to prevent axillary surgery. It seems that the prediction model presented in this study, based on the results of the neuromography, can help surgeons make a more informed decision on underarm surgery. Moreover, in some cases, their surgical program will be informed by accurate medical care and preclusion of major surgeries such as ALND.

Vitamin D receptor gene polymorphisms and risk of breast cancer in Iranian women

ObjectivesVitamin D deficiency is a driving force of common cancers like breast cancer. Vitamin D receptor (VDR) can play a tumor suppressor role by helping the precise function of vitamin D in cells such as modulation TGF-β signaling pathway. This study aimed to investigate the association of VDR gene variants and susceptibility to breast cancer in Iranian women. MethodsGenomic DNAs were isolated from blood samples of 161 women with breast cancer and 150 healthy women. After amplification of five positions of VDR gene, the prepared amplicons were digested with TaqI, ApaI, BsmI, Cdx2, and FokI restriction enzymes. ResultsSubsequently, the digested products were electrophoresed on the 1.5% agarose gel. Odds ratios (ORs) for breast cancer were calculated for genotypes and estimated haplotypes. Binary logistic regression analysis showed FokI (rs2228570), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms had the significant distribution in patients than to the normal group. Analysis of linkage disequilibrium for all pairs of SNPs showed that D′-value between SNP TaqI and SNP BsmI was significantly (p ≤ 0.05). We observed that four major haplotypes of ApaI, BsmI, FokI, Cdx2, and TaqI SNPs significantly were in high frequency than predicted frequency. Among these four haplotypes, CGTAT haplotype was in a higher significant association than others with breast cancer risk (p-value = 0.0001). ConclusionOur results showed that FokI, BsmI, and ApaI of VDR polymorphisms associated with the risk of breast cancer in Iranian population.

A Case-Control Study on the p73 G4A Gene Polymorphism and Susceptibility to Breast Cancer in an Iranian Population

The tumor protein p73 (TP73) is a homolog of TP53 family. Ectopic p73 overexpression largely mimics p53 activities as a tumor suppressor and activates the transcription of p53-responsive genes and as a result induce apoptosis. This study aimed to investigate the association between p73 G4A polymorphism and the risk of breast cancer in a northeastern Iranian population. This case-control study was performed on 105 patients who admitted in educational hospitals of Mashhad University of Medical Sciences, Iran during 2013-2015, with breast cancer as case group and 120 healthy women as the control group. PCR-CTPP method was used to investigate the relationship between the p73 G4A polymorphism and the risk of breast cancer. There was no significant association between the AA genotype of the p73 G4A polymorphism and breast cancer in case and control groups. Although G allele frequency was higher in the case group, the abundance of this allele between case and control groups was not statistically meaningful and, as a result, not associated with the risk of breast cancer in this study group. There was no association between G4A p73 polymorphism and the risk of breast cancer in a northeastern Iranian population.

The NCCN Criterion "Young Age at Onset" Alone is Not an Indicator of Hereditary Breast Cancer in Iranian Population.

Because the contribution of genetic factors to the burden of breast cancer is not well investigated in Iran, we aimed to examine the prevalence of mutations in breast cancer susceptibility genes, BRCA1/2 and PALB2, and to investigate the predictive potential of hereditary breast cancer risk criteria for genetic testing in Iranian population. Next-generation sequencing was conducted on a population consisting of 299 and 125 patients with breast cancer, with and without hereditary cancer risk criteria for genetic testing, respectively. The pathogenic mutation frequency rate was 10.7% in patients with hereditary cancer criteria versus 1.6% in no criteria group (P = 0.0017). None of the 107 tested patients with only young age at onset (<40) criterion had a pathogenic mutation. Patients who had only a single heritable risk criterion [OR, 6.15; 95% confidence interval (CI), 1.26-58.59; P = 0.009] and patients with multiple heritable risk criteria (OR, 22.5; 95% CI, 5.19-201.31; P < 0.0001) had higher probabilities of carrying a mutation compared with no criteria group. Our results showed that young age at onset alone is not an indicator of hereditary breast cancer at least in the Iranian population. This is while women with multiple hereditary breast cancer risk criteria were enriched for BRCA1/2 mutations. Given such high risk of identification of a disease-causing mutation, multiple hereditary criteria should be regarded as a strong predictor for a hereditary breast cancer syndrome. These findings are important concerning the optimization of genetic counseling and furthermore establishing criteria for BRCA1/2 testing of the Iranian population.

Genomic variants within the long non-coding RNA H19 confer risk of breast cancer in Iranian population

ObjectiveThe long non-coding RNA (lncRNA) H19 is an imprinted lncRNA with acknowledged roles in carcinogenesis. MethodsIn the current study, we genotyped two single nucleotide polymorphisms (SNPs) within H19 in 111 breast cancer patients and 130 age-matched healthy subjects using tetra primer-ARMS-PCR technique. The T allele of rs2839698 conferred breast cancer risk in the assessed population (OR (95% CI) = 2.52 (1.75–3.64), adjusted P value = 1.3E-6), while and the T allele of rs217727 had a protective effect (OR (95% CI) = 0.42 (0.27–0.66), adjusted P value = 2.8E-4). Both SNPs were associated with breast cancer risk in recessive, dominant and co-dominant models. The T C haplotype (rs2839698 and rs217727) significantly increased risk of breast cancer (OR (95% CI) = 2.4 (1.65–3.45), adjusted P value = 1.2E-5), while the C T haplotype had a protective role (OR (95% CI) = 0.31 (0.18–0.52), adjusted P value = 2.03E-5). The present study highlights the role of H19 SNPs in conferring risk of breast cancer in Iranian population. Future studies with larger sample sizes are required to verify these data.

FOXP3 GENE POLYMORPHISM IS ASSOCIATED WITH BREAST CANCER IN IRANIAN PATIENTS

Breast cancer (BC) is one of the leading causes of cancer death among women. Recent studies have characterized FoxP3 as a marker of regulatory T cells and an X-linked tumor suppressor gene, which is involved in the pathogenesis of BC. Therefore, we investigated the potential influence of three single-nucleotide polymorphisms (SNPs) of FoxP3 gene on the development of BC in Iranian women. The association between FoxP3 rs2232365, rs3761548 and rs4824747 polymorphisms and BC risk was assessed in 124 BC patients and 198 healthy controls using sequence-specific primers. We identified significant difference of rs3761548 in both allele and genotype frequencies between cases and control groups. Our results showed that individuals carrying FoxP3 rs3761548 AA genotype had about 4.3-fold increased risk of BC compared with CC carriers. No significant association was found between rs3761548C>A polymorphism and clinical outcome parameters (age of onset, tumor size, lymph nodes metastasis, tumor stage, progesterone receptor status, estrogen receptor status, Ki-67 status, HER-2 status and duration of disease). This study has provided the first genetic data on the FoxP3 gene polymorphism in south of Iran and proposes the rs3761548 polymorphism of FoxP3 gene as a risk factor, but not a prognostic marker in the development of BC in Iranian population.

Significant association of TOX3/LOC643714 locus-rs3803662 and breast cancer risk in a cohort of Iranian population.

Genome-wide association studies normally focus on low penetrance and moderate to high-frequency single nucleotide polymorphisms (SNPs), which lead to genetic susceptibility to breast cancer. In this regard, the T allele of rs3803662 has been associated with breast cancer risk and with lower expression level of TOX3. We aimed to assess the risk of breast cancer associated with this polymorphism in an Iranian population. Using Tetra Primer ARMS PCR, rs3803662 was analyzed in a total of 943 individuals (430 cases and 513 healthy controls form North East of Iran). Allele frequencies and genotype distribution were analyzed in case and control samples to find out any association using the Chi-squared test and Logistic regression. All cases were pathologically confirmed; all controls were mainly healthy individuals. Genotype frequencies were found to be in agreement with HWE in controls and cases. TOX3-rs3803662 SNP was associated with breast cancer risk in our study (T vs. C allele contrast model: OR 1.36, 95% CI 1.12-1.64, Pvalue = 0.002; TT vs. CT + TT dominant model: OR 0.67, 95% CI 0.51-0.87, Pvalue = 0.003; TT vs. CT + CC recessive model: OR 1.54, 95% CI 1.02-2.30, Pvlue = 0.036). Moreover, after adjusting for age, BMI, history of previous cancer and also family history of cancer, all results, except for the recessive model, were remained significant. TOX3-rs3803662, may confer some degrees of risk of breast cancer in Iranian population. This finding is in line with similar results in other populations. It highlights the importance of TOX3 pathway in tumorigenesis.

Assessment of Genetic Aspects of Breast Cancer in Iranian Population (a Review Study)

Assessment of Genetic Aspects of Breast Cancer in Iranian Population (a Review Study)

Association between rs11614913, rs3746444, rs2910164 and occurrence of breast cancer in Iranian population

BackgroundBreast cancer is a complex and heterogeneous disease that has several subgroups with different clinical outcomes. This disease is the second leading cause of cancer after lung cancer. The incidence of this cancer is high among women, and it is one of the major causes of death among them. Determining the susceptibility of the patient to the disease and consequently using appropriate methods for early detection of the disease play a significant role in prognosis and survival rate of the patient. Therefore, studies which identify markers of susceptibility to the disease and consequently the use of early detection strategies are considered as one of the attractive areas of research in the field of cancer genetics. ObjectivesIn this study the association of rs11614913, rs3746444 and rs2910164 polymorphisms with breast cancer was examined in hsa-mir-196a2 and hsa-mir-499 and hsa-mir146a genes respectively. MethodsThe present case–control study was included 100 patients with breast cancer and 150 healthy controls. After DNA extraction, genotypic distribution of SNPs rs11614913, rs3746444 and rs2910164 was examined in hsa-mir-196a2, hsa-mir-499 and hsa-mir146a genes respectively via ARMS-PCR for both groups. The frequency of various alleles of each polymorphism was examined in both control and study groups using Pearson chi-square test. The P values less than 5% were considered as significant differences between the two groups. Finally, the odds ratio of each allele and genotype was studied. ResultsAfter comparing the frequency of polymorphisms in two groups, a significant association was found between the occurrence of breast cancer in Iranian population and rs3746444 (P-value<0.05). Other polymorphisms were not significantly associated with the incidence of breast cancer (P-value>0.05). The results indicated an increased risk of breast cancer in patients with C allele compared to patients without this allele. ConclusionAccording to our results rs3746444 has a significant association with occurrence of breast cancer in Iranian population.

CCL22 16C/a genetic variation is not associated with breast carcinoma in Southern Iranian population.

CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis. To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population. 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 age-matched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium. The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population. No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.

NADPH oxidase gene variant (rs13306294-A/G) in coronary artery disease (CAD) patients and normal subjects

Breast cancer is a complex and heterogeneous disease that has several subgroups with different clinical outcomes. This disease is the second leading cause of cancer after lung cancer. The incidence of this cancer is high among women, and it is one of the major causes of death among them. Determining the susceptibility of the patient to the disease and consequently using appropriate methods for early detection of the disease play a significant role in prognosis and survival rate of the patient. Therefore, studies which identify markers of susceptibility to the disease and consequently the use of early detection strategies are considered as one of the attractive areas of research in the field of cancer genetics.In this study the association of rs11614913, rs3746444 and rs2910164 polymorphisms with breast cancer was examined in hsa-mir-196a2 and hsa-mir-499 and hsa-mir146a genes respectively.The present case–control study was included 100 patients with breast cancer and 150 healthy controls. After DNA extraction, genotypic distribution of SNPs rs11614913, rs3746444 and rs2910164 was examined in hsa-mir-196a2, hsa-mir-499 and hsa-mir146a genes respectively via ARMS-PCR for both groups. The frequency of various alleles of each polymorphism was examined in both control and study groups using Pearson chi-square test. The P values less than 5% were considered as significant differences between the two groups. Finally, the odds ratio of each allele and genotype was studied.After comparing the frequency of polymorphisms in two groups, a significant association was found between the occurrence of breast cancer in Iranian population and rs3746444 (P-value < 0.05). Other polymorphisms were not significantly associated with the incidence of breast cancer (P-value > 0.05). The results indicated an increased risk of breast cancer in patients with C allele compared to patients without this allele.According to our results rs3746444 has a significant association with occurrence of breast cancer in Iranian population.

Estrogen Receptor-α Gene, Codon 594 (G3242A) Polymorphism Among Iranian Women with Breast Cancer: A Case Control Study

A case-control study was conducted to establish a database of ESR1 polymorphisms in Iranian population in order to compare Western and Iranian (Middle East) distributions and to evaluate ESR1 polymorphism as an indicator of clinical outcome. The ESR1 gene was scanned in Iranian patients newly diagnosed invasive breast tumors, (150 patients) and in healthy individuals (147 healthy control individuals). PCR single-strand conformation polymorphism technology and direct sequencing was performed. The silent single nucleotide polymorphism (SNPs) was found, as reported previously in other studies, but at significantly different frequencies. The frequency of genotype 01 in codon 594 (ACG-ACA), (G3242A), exon 8 was significantly higher in breast cancer patients (48.0%) than in control individuals (1.4%; p = 0.001). The allele 1 in codon 594 was significantly more common in breast cancer patients with age at menarche </=12 (40.8%) than in those which their menstruation began at older than 12 years old (23.9%; p = 0.002). The allele 1 in codon 594 exhibited, the greater the frequency, the lesser the likelihood of LN metastasis. Present results demonstrated that this particular SNP marker may increase accuracy in predicting LN. Therefore, this SNP marker further increased predictive accuracy in Iranian population. These data suggest that ESR1 polymorphisms are correlated with various aspects of breast cancer in Iranian ESR1 genotype, as determined during pre-surgical evaluation, might represent a surrogate marker to increase predicting breast cancer in Iranian population.