scholarly journals An Interdependence between Estrogen Receptor 1 Gene Polymorphisms and Susceptibility to Breast Cancer

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Maryam Saneipour ◽  
Abdolkarim Sheikhi ◽  
Abbas Moridnia

Background: Breast cancer (BC) is the most common malignant tumor in women around the world. Genetic factors do play a vital role in the development and progression of BC. Genetic alterations in the ESR1 (estrogen receptor 1) gene can lead to estrogen dysfunction and increased risk for BC. Nevertheless, due to genetic diversity, the information from different studies is contradictory and controversial. Objectives: This study aimed to investigate the potential relationship between the rs1801132 and rs2234693 single nucleotide polymorphism (SNPs) of the ESR1 gene with susceptibility to BC in the Iranian population. Methods: The genotyping of the rs2234693 and rs1801132 SNPs was assessed in 63 BC patients referred to Imam Hasan Mojtaba Center, which is a charity-based foundation for cancer care in Dezful, Iran, from March 2018 to November 2019. Also, 65 healthy women were selected as a control group. The genotyping of the SNPs was performed using the high-resolution melting (HRM) technique and confirmed by DNA sequencing. Results: The genotype distribution and allele frequency of the rs2234693 SNP were significantly different in BC patients compared to the control group (genotype frequency with P = 0.018 and allele frequency with P = 0.004, OR = 2.085, 95% CI = 1.253 -3.468). In genetic models, rs2234693 increased BC risk in recessive model (P = 0.005, OR = 2.813, 95% CI = 1.363 - 5.802). However, there was no significant difference regarding genotype distribution of the rs1801132 SNP between the BC patients and controls. Conclusions: Our results showed that the CC genotype of the rs2234693 SNP is significantly associated with BC. Accordingly, it can be suggested that the rs2234693 SNP be considered for susceptibility to BC.

2021 ◽  
Vol 32 (2) ◽  
pp. 79-84
Author(s):  
Kevin Owen ◽  
Siti Syarifah ◽  
Mutiara Indah Sari

Background: Oxidative stress induced cancer cell formation. Gene polymorphism plays roles in carcinogen metabolism, antioxidant and DNA repairing pathway was susceptibility to oxidative stress. This study aim to determine the association between CAT-21 A/T polymorphism with breast cancer susceptibility. Methods: Case control study was conducted on 65 breast cancer patient and 65 healthy control group. The whole blood samples were isolated from 65 breast cancer patients in Haji Adam Malik General Hospital Medan and 65 healthy control group. The CAT-21A/T polymorphism was analyzed by PCR-RFLP procedure. PCR-RFLP product was electrophoresed and visualized in agarose 4%. Results:The AA CAT-21 genotype were lower in breast cancer (BC) than healthy control (HC) group (31/47.7% vs 40/61.5%), in the contrary AT+TT genotype was greater in BC than HC group (34/52.3% vs 25/38.5%) with (p=0.159, OR=1.755, CI=0.874–3.525). A allele CAT-21 were found lower in BC than HC group (89/68.5% vs 105/80.8%) then T allele were greater in BC than HC group (41/31.5% vs 25/19.2%) with (p=0.033, OR=1.935;CI=1.022-3.428). Conclusions: There was significant difference in allele distribution of CAT-21 A/T between case and control group but no in genotype distribution. In this population study showed that allele of CAT -21 A/T polymorphism could represent as a risk factor to breast cancer. Bangladesh J Medicine July 2021; 32(2) : 79-84


Author(s):  
Chandan K. Jha ◽  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Naina Khullar ◽  
Suriya Rehman ◽  
...  

Aim: Studies have evaluated the association of miRNA-423 C>A genotyping with the susceptibility to various diseases such cancers, atherosclerosis and inflammatory bowel disease but the results were contradictory. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of coronary artery disease. MicroRNAs regulate expression of multiple genes involved in atherogenesis. Therefore, we investigated the association of microRNA-423C>T gene variations with susceptibility to coronary artery disease. Methodology: This study was conducted on 100 coronary artery disease patients and 117 matched healthy controls. The genotyping of the microRNA-423 rs6505162C>A was performed by using Amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution among the coronary artery disease cases and sex-matched healthy controls (P=0.048). The frequencies of all three genotypes CC, CA, AA reported in the patient’s samples were 55%, 41% and 4% and in the healthy controls samples were 55%, 41% and 4% respectively. Our findings showed that the microRNA-423 C>A variant was associated with an increased risk of coronary artery disease in codominant model (OR = 1.96, 95 % CI, 1.12-3.42; RR 1.35(1.05-1.75, p=0.017) of microRNA-423CA genotype and significant association in dominant model (OR 1.97, 95% CI (1.14-3.39), (CA+AA vs CC) and non-significant association for recessive model (OR=1.42, 95%CI=0.42-4.83, P=0.56, AA vs CC+CA).While, the A allele significantly increased the risk of coronary artery disease (OR =1.56, 95 % CI, 1.03-2.37; p=0.035) compared to C allele. Therefore, it was observed that more than 1.96, 1.97 and 1.56 fold increased risk of developing coronary artery disease. Conclusion: Our findings indicated that microRNA-423 CA genotype and A allele are associated with an increased susceptibility to Coronary artery disease.


Author(s):  
Juan Carlos Esparza-García ◽  
David Santiago-Germán ◽  
María Guadalupe Valades-Mejía ◽  
Jesus Hernández-Juárez ◽  
Eberth Aguilar-Sosa ◽  
...  

AbstractBackground: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. Materials and Methods: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. Results: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). Conclusions: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jialei Chen ◽  
Jing He ◽  
Jing Luo ◽  
Shixun Zhong

Objective: The etiology of sudden sensorineural hearing loss (SSNHL) is still unknown. It has been demonstrated that normal endolymph metabolism is essential for inner ear function and that epithelial sodium channels (ENaC) may play an important role in the regulation of endolymphatic Na+. This study aimed to explore the potential association between αENaC p. Ala663Thr gene polymorphism and SSNHL.Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype and allele frequency of the αENaC p. Ala663Thr polymorphism in 20 cases of low-frequency SSNHL (LF-SSNHL), 19 cases of high-frequency SSNHL (HF-SSNHL), 31 cases of all frequency SSNHL (AF-SSNHL), 42 cases of profound deafness SSNHL (PD-SSNHL), and 115 normal controls.Results: The T663 allele was found to be significantly associated with an increased risk of LF-SSNHL (p = 0.046, OR = 2.16, 95% CI = 1.01–4.62). The TT genotype and T663 allele, on the other hand, conferred a protective effect for PD-SSNHL (AA vs. TT: p = 0.012, OR = 0.25, 95% CI = 0.08–0.74; A vs. T: p = 0.001, OR = 0.36, 95% CI = 0.21–0.61). However, there was no statistically significant difference in genotype or allele frequency between the two groups (HF-SSNHL and AF-SSNHL) and the control group.Conclusion: The αENaC p. Ala663Thr gene polymorphism plays different roles in different types of SSNHL.


Author(s):  
Rashid Mir ◽  
Faisel M. Abu-Duhier ◽  
Ibrahim Altedlawi Albalawi

Aim: Hypoxia-inducible factor 1 (HIF-1) is responsible in regulating oxygen homeostasis in tissues. HypoxiaInducible Factor α (HIF1-α) is a central effector of the hypoxic response. HIF-1α protein overexpression has been shown to have prognostic relevance in breast cancer. HIF-1α polymorphism is associated with increased breast susceptibility reported by several case controls studies but results remained controversial. Therefore, we studied the relationship between the HIF1α gene polymorphism with the breast cancer risk in Saudi Arabia. Methods: This study was consisted of 114 histologically confirmed Breast cancer patients and 117 sex -matched healthy women. HIF-1α genotyping was done by Amplification refractory mutation system PCR method. The HIF-1α gene genotypes were correlated with different clinicopathological characteristics of breast cancer patients. Results: A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T between breast cancer cases and sex matched healthy controls (p=0.001). Our findings showed that the HIF- 1α variant was associated with an increased risk of Breast cancer for HIF-1α CC vs CT genotype OR = 0. 38, 95% CI = (0. 22 -0. 65), P = 0.005) in codominant inheritance model. The significant association was reported for HIF1A for genotypes CC vs (CT+ TT) OR = 0. 39, 95% CI = (0. 231 -0. 67), P = 0.007) in dominant inheritance model tested. In case of recessive inheritance model, a significant association of HIF-1 alpha gene variants was reported for CC VS -(CC+ CT) vs TT) OR = 3.10, 95% CI = (0. 12- 77.03), P = 0.56). During the allelic comparison, A allele significantly increased the risk of Breast cancer with odd ratio (OR = 0. 66, 95% CI = 0. 53 -1. 21, P = 0.04) and risk ratio RR= 0. 51 (0. 32 -0. 80) P= 0.004). A significant association of HIF1α polymorphism was reported with stage as well as distant metastasis of the disease. Conclusion: A significant association of HIF- 1α-CT heterozygosity and T allele significantly increased the susceptibility and is associated with the metastasis of Breast cancer. Further studies with larger data set and well-designed models are required to validate our findings.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2823-2823
Author(s):  
Kathy L. McGraw ◽  
Lan Min Zhang ◽  
William Fulp ◽  
Hui-Yi Lin ◽  
Andres Jerez ◽  
...  

Abstract Abstract 2823 Background: Mutations in TP53, or less often its regulators, increases risk for malignant transformation. Murine double minute protein 2 (MDM2), an E3 ubiquitin ligase, targets p53 for proteasomal degradation and is the most well studied negative regulator of p53. Recent investigations have highlighted the emerging importance of p53 in MDS. Haploinsufficiency for ribosomal protein S14 in deletion 5q MDS liberates free ribosomal proteins that bind to and promote degradation of MDM2, thereby activating p53 in erythroid precursors. A single nucleotide polymorphism (SNP) in an MDM2 promoter (SNP309) is linked to younger age of onset of several solid tumors and an increased risk for acute myeloid leukemia (AML) [Knappskog and Lonning. 2011. Transcription 2:207, Xiang et al. 2009. Leuk Res. 33:1454]. The thymine (T) to guanine (G) substitution introduces an additional Sp1 transcription factor binding site causing upregulation of MDM2 transcription. A second SNP in this promoter (SNP285) has also been linked to cancer susceptibility, where a guanine (G) to cytosine (C) exchange is associated with decreased ovarian and breast cancer risk (Knappskog and Lonning. 2011. Oncotarget. 2:251). The C-allele of SNP285 has diminished Sp1 promoter binding compared to the G-allele decreasing MDM2 expression. In this study we investigated genotype distribution of MDM2 SNPs in del(5q) and non-del(5q) MDS patients and compared results to healthy controls. Methods and Results: Using Sanger sequencing, we compared allele and genotype frequencies for SNP285 and SNP309 in 155 healthy controls, 97 non-del(5q), and 119 del(5q) MDS patients. For SNP285, we found no significant difference in genotype or allele frequency among non-del(5q) or del(5q) cases compared to controls (p=0.25 and 0.26, respectively). Although there was no difference in age at diagnosis by genotype in del(5q) MDS (p=0.82), there was a significant difference among non-del(5q) MDS cases [p<0.01, mean (range) for GC:80.8y (75–89) and GG:68.9y (27–91)], however, the frequency of the GC genotype was low [n=5, non-del(5q); n=11, del(5q)] with no CC genotype cases. For SNP309, there was no difference in allele frequency (p=0.68), however genotype frequency differed between controls, non-del5q, and del5q MDS (p=0.06). The genotype distribution was significantly different between non-del(5q) and del(5q) MDS (p=0.01). SNP309 genotype frequencies for controls, non-del(5q), and del(5q) MDS were GG:17.3%, 22.7%, 10.1%; TG: 42.9%, 37.1%, 53.8%; TT: 39.7%, 40.2%, 36.1%, respectively. We found no difference in age of disease onset by SNP309 genotype in either non-del(5q) or del(5q) cases (p=0.08 and 0.97, respectively). There was no significant relationship between SNP285 genotype and IPSS (p=1.0), cytogenetic risk (p=0.66), or WHO classification (p=0.16) in non-del(5q) or del(5q) cases (p=1.0, 0.78, and 0.60, respectively). Similar results were observed for SNP309 [p=0.85, 0.39, and 0.68 for non-del(5q); p= 0.06, 0.98, 0.27 for del(5q), respectively]. For SNP285 there was no difference in overall survival (OS) by genotype in either non-del(5q) (p=0.65) or del(5q) MDS (p=0.72). Progression free survival (PFS) also did not differ by genotype in non-del(5q) (p=0.82) or del(5q) (p=0.58) patients. There was a significant difference in LEN response rate in del(5q) MDS (p=0.04, non-responders: 23.8% GC and 76.2% GG, responders: 4.9% GC and 95.1% GG), however, genotype did not influence response duration (p= 0.40). For SNP309, there were no significant difference in OS by genotype (p=0.42), PFS (p=0.78), LEN response rate (p=0.17), or response duration in del(5q) MDS (p=0.65). In non-del(5q), there was no difference in OS (p=0.42), LEN response rate (p=0.91), or response duration (p=0.47). However, we found a significant difference in PFS by genotype (p=0.03) with more prolonged PFS in patients with the heterozygous TG genotype (60 mo PFS: GG 55.3%, TT 54.1%, and TG 81.7%). Finally, we found no difference in chromosome 5 deletion size or deletion location in del(5q) MDS according to SNP309 genotype. Conclusions: MDM2 SNP309 may be linked to MDS susceptibility, as well as LEN responsiveness and PFS in del(5q) and non-del(5q) MDS, respectively. These data warrant validation in a larger patient cohort. Investigation of the interaction between MDM2 SNPs and the well described TP53 R72P SNP is underway. Disclosures: List: Celgene: Consultancy.


2020 ◽  
Vol 26 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Nikolina Dukic ◽  
Zdenka Gojkovic ◽  
Jelena Vladicic-Masic ◽  
Srdjan Masic ◽  
Nenad Lalovic ◽  
...  

Background: Of all breast cancers 20-25% are HER2 positive. Overexpression of HER2 protein on the surface of the malignant cell leads to excessive cell proliferation through different signaling pathways. Trastuzumab is a human monoclonal antibody that binds to domain IV of HER2 receptor and blocks signaling pathway for proliferation. The result is an improved prognosis for HER 2 positive breast cancer patients, even when compared to patients with other types of breast cancers. Methods: The study presents 74 women patients with early HER2 positive breast cancer who were previously operated (either radicaly or using breast conserving surgery), and received adjuvant chemo- and radiotherapy. Fourty four patients received adjuvant trastuzumab for one year, and 30 patients did not (control group). Observed time to relapse of the disease was 60 months. Results: There was a significant difference in survival in favor of the group that received trastuzumab (p<0.001). Application of trastuzumab also delayed relapse of the disease by 51.7%. No significant difference was observed between estrogen receptor positive and estrogen receptor negative cancers., In the control group there was a significant difference in relapse free survival in favor of estrogen and progesteron receptor positive tumors (p<0.001). Conclusion: Survival of patients with a HER2 positive breast cancer whose prognosis was initially worse compared to HER2 negative patients, significantly improved after administration of trastuzumab.


2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Juan Wang ◽  
Hongliang Ji ◽  
Helei Jia ◽  
Dongsheng Guan

Abstract Using a case–control design, we assessed the association between single nucleotide polymorphisms of CYP3A4 gene rs4646437 polymorphism and the risk of hypertension in Chinese population. We recruited 450 hypertension patients from The First Clinical College, Henan University of Chinese Medicine between June 2017 and May 2018. There was a significant difference in genotype distribution between case group and control group (χ2=18.169, P=0.000). The minor A allele was significantly higher in the case group than that in the control group (31.0 vs 24.8%, P=0.000, odds ratio [OR]=1.36, 95% confidence interval [95% CI]: 1.12–1.66). Significant differences were also observed in other gene models: the GA/AA genotype did not increase the risk of hypertension compared with GG genotype (OR=1.16, 95% CI: 0.90–1.49, P=0.259). Compared with GG/GA genotype, the AA genotype also increased the risk of hypertension (OR=2.34, 95% CI: 1.56–3.50, P=0.000). For additive model, the AA genotype was significantly associated with GG genotype (OR=2.25, 95% CI: 1.49–3.42, P=0.000). The same results were found for AA vs GA (OR=2.50, 95% CI: 1.60–3.89, P=0.000). For the allele genotype, the A allele frequency was significantly higher in the case group than that in the control group (31.0 vs 24.8%, P=0.002). The A allele of CYP3A4 rs4646437 was associated with an increased risk for hypertension (OR=1.36, 95% CI: 1.12–1.66, P=0.002). Our results revealed a possible genetic association between CYP3A4 gene rs4646437 and hypertension, and the AA genotype of rs4646437 increased the risk of hypertension in Chinese Han population, and this effect could be confirmed by multivariable analyses.


2009 ◽  
Vol 19 (6) ◽  
pp. 1011-1014 ◽  
Author(s):  
Qifang Tian ◽  
Weiguo Lu ◽  
Huaizeng Chen ◽  
Feng Ye ◽  
Xing Xie

Background:It was suggested that single-nucleotide polymorphisms in p21 codon 31 seem to be associated with a variety of human malignancies; very few studies have focused on the association between p21 codon 31 polymorphisms and cervical cancer. This study explored whether p21 codon 31 nonsynonymous single-nucleotide polymorphisms might be associated with an increased risk of cervical cancer development among Chinese women.Methods:Peripheral blood samples were obtained from patients with cervical cancer (n = 317) and healthy controls (n = 353) for detecting the biallelic polymorphisms at codon 31 of p21 gene by the mismatch amplification mutation assay-polymerase chain reaction. Cervix brush-off samples were obtained from patients with cervical squamous cell carcinoma (SCC) and controls for detection of high-risk human papillomavirus (HR-HPV).Results:The AGA (Arg) allele frequency in patients with cervical SCCs was significantly higher than that in controls. AGA/AGA and AGA/AGC genotypes were more frequently found in cervical SCCs than in controls. There was no significant difference of allele frequency or genotype distribution between cervical adenocarcinomas and controls, or between HR-HPV-positive and HR-HPV-negative groups.Conclusions:p21 Codon 31 with AGA (Arg) allele is a genetic risk factor of cervical SCC, and the increased risk is probably not caused by increasing host susceptibility to HR-HPV infection.


2018 ◽  
Vol 4 ◽  
pp. 3-13
Author(s):  
Yuriy Dumanskiy ◽  
Oleksandr Bondar ◽  
Oleksandr Tkachenko ◽  
Evhenii Stoliachuk ◽  
Vasilii Ermakov

In recent years, breast cancer (BC) is the most common cancer pathology and the most common cause of disability among women in developed countries. Finding the most effective ways of interaction between the patient and the doctor creates the preconditions for the necessary analysis of the treatment process from an objective and subjective point of view. Therefore, an important indicator to be taken into account is the quality of life of a patient. To compare the indicators of a comprehensive assessment of the quality of life of patients to the adverse locally advanced forms (LA) of breast cancer before and after systemic intravenous polychemotherapy (SPCTx) and selective endolymphatic polychemotherapy (ELPCTx) in neoadjuvant mode. The study was conducted on the basis of a random analysis of outpatient cards from 112 patients with LA BC T4A-DN0-3M0 who received a comprehensive antitumor treatment on the basis of the Donetsk regional antitumor center and the University Clinic of the Odessa National Medical University from 2000 to 2017, which was proposed a questionnaire at various stages of preoperative treatment. The first (control) group consisted of 65 patients (58 %) with inoperable forms of LA BC, which was performed in neoadjuvant mode by SPCTx. The second (study group) included 47 patients (42 %) with inoperable forms of LA BC, which was performed as a neoadjuvant course ELPCTx. According to the integral indicators of quality of life and quality of health between patients in the control and study groups, there was no statistically significant difference. In a detailed analysis of the indicators of symptomatic scales, the difference between the groups did not exceed the critical. Based on the results of a study conducted among patients receiving endolymphatic chemotherapy in a neoadjuvant mode, the subjective evaluations of treatment in absolute numbers have better reference values without statistical superiority. The study of the integrative indicator of quality of life and its discrete elements is an ergonomic and economical means of heuristic assessment of the health of patients in order to further develop more rational and convenient ways of solving urgent issues of modern oncology by increasing compliance and finding a compromise between the physician and the patient.


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