INTERACTION BETWEEN POLYMORPHIC VARIANTS IN ТP53, XRCC1, TNFH, HMMR, MDM2,PALB2 GENES AND THEIR CONTRIBUTIONTO THE FORMATION OF A PREDISPOSITION TO BREAST CANCER IN WOMEN OF THE KYRGYZ POPULATION

2019 ◽  
Vol 65 (3) ◽  
pp. 357-367
Author(s):  
Zhaynagul Isakova ◽  
Vyacheslav Kipen ◽  
Elnura Talaybekova ◽  
Kubanych Aytbaev ◽  
N. Aldasheva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rflp Analysis ◽  
Nucleotide Polymorphisms ◽  
Heterozygous Genotype ◽  
Single Nucleotide ◽  
Polymorphic Loci ◽  
Pcr Rflp ◽  
Gene Tp53 ◽  
Polymorphic Variants ◽  
Kyrgyz Population

Aim: We studied the intergenic interactions and the contribution of polymorphic loci p.Arg72Pro (gene TP53), p.Gln399Arg (gene XRCC1), p.Arg194Trp (gene XRCC1), g.4682G>A (gene TNFa), p.Val353Ala (gene HMMR), p.14+309T>G (gene MDM2), g.38444T>G (gene PALB2) in the formation of predisposition to breast cancer (ВС) in women of Kyrgyz nationality. Material and method: The study included 103 women of the Kyrgyz ethnic group with the morphologically verified diagnosis of BC and 102 women without cancer and chronic diseases. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using PCR-RFLP. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Results: Heterozygous genotype Gln/Arg of gene XRCC1 (ОR=3,15; 95% CI 1,78-5,58), the combination of Arg/Gln // Arg/Pro of genes XRCC1 (p.Gln399Arg) / TP53 (p.Arg72Pro) (OR=3,21; 95% CI 1,21-8,47), Arg/Gln // T/T of genes XRCC1 (p.Gln399Arg) / MDM2 (o.14+309T>G) (OR=3,18; 95% CI 0,99-10,7), Arg/Gln // G/G and Arg/Gln // G/A of genes XRCC1 (p.Gln399Arg) / TNFa (g.4682G>A) (OR=3,84; 95% CI 1,847,90) and (OR=3,91 95% CI 1,29-8,51 respectively), Arg/Gln // T/T of genes XRCC1 (p.Gln399Arg) / PALB2 (p.Thr1100=) (OR=2,92; 95% CI 1,59-5,37), as well as Arg/Gln // Arg/Arg and Arg/Gln // Arg/Trp for polymorphic loci p.Gln399Arg and p.Arg194Trp of gene XRCC1 (OR=2,48; 95% CI 1,12-5,19 and 0R=2,90, 95% CI 1,04-8,12 respectively) were associated with BC in Kyrgyz women. Conclusions: The results of the present study suggest that combinations of variants of ТP53, XRCC1, TNFa, HMMR, MDM2 и PALB2 genes may contribute to the genetic susceptibility of BC in Kyrgyz women.

scholarly journals The Investigation of Associations between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344, EGFR rs2227983 Polymorphisms and Breast Cancer Phenotype and Prognosis

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1419
Author(s):  
Justina Bekampytė ◽  
Agnė Bartnykaitė ◽  
Aistė Savukaitytė ◽  
Rasa Ugenskienė ◽  
Erika Korobeinikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Cancer Prognosis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cox Regression Analysis ◽  
Pcr Rflp ◽  
Oncological Diseases ◽  
Cancer Phenotype

Breast cancer is one of the most common oncological diseases among women worldwide. Cell cycle and apoptosis—related genes TP53, BBC3, CCND1 and EGFR play an important role in the pathogenesis of breast cancer. However, the roles of single nucleotide polymorphisms (SNPs) in these genes have not been fully defined. Therefore, this study aimed to analyze the association between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344 and EGFR rs2227983 polymorphisms and breast cancer phenotype and prognosis. For the purpose of the analysis, 171 Lithuanian women were enrolled. Genomic DNA was extracted from peripheral blood; PCR-RFLP was used for SNPs analysis. The results showed that BBC3 rs2032809 was associated with age at the time of diagnosis, disease progression, metastasis and death. CCND1 rs9344 was associated with tumor size, however an association resulted in loss of significance after Bonferroni correction. In survival analysis, significant associations were observed between BBC3 rs2032809 and OS, PFS and MFS. EGFR rs2227983 also showed some associations with OS and PFS (univariate Cox regression analysis). However, the results were in loss of significance (multivariate Cox regression analysis). In conclusion, BBC3 rs2032809 polymorphism was associated with breast cancer phenotype and prognosis. Therefore, it could be applied as potential markers for breast cancer prognosis.

scholarly journals Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses

Reproduction ◽  
2006 ◽  
Vol 131 (2) ◽  
pp. 395-401 ◽  
Author(s):  
N Mtiraoui ◽  
W Zammiti ◽  
L Ghazouani ◽  
N Jmili Braham ◽  
S Saidi ◽  
...  
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Rflp Analysis ◽  
Mthfr C677t ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Recurrent Pregnancy Losses ◽  
Total Homocysteine ◽  
A1298c Polymorphism ◽  
Early Late

Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P= 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P< 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P< 0.05) and early-late (P< 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in early-late RPL (P< 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P= 0.10; odds ratio = 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P< 0.001), and combined early-late (P< 0.001), while homozygosity for A1298C was associated only with combined early-late (P= 0.026), as was secondary-level education, which was associated with early (P= 0.005), late (P= 0.026) and combined early-late (P= 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels.

The role and interaction of polymorphic variants of non-allelic genes ADIPOQ, MTHFR, PON1, KCNJ11, TCF7L2, ITLN1, PPARG in the increase in the risk of obesity in Kyrgyz Republic

2021 ◽  
pp. 44-56
Author(s):  
Ж.Т. Исакова ◽  
В.Н. Кипень ◽  
Кызы Самара Акынбек ◽  
К.А. Айтбаев ◽  
Н.М. Алдашева ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Kyrgyz Republic ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pcr Rflp ◽  
Increase Risk ◽  
Obese Control ◽  
Polymorphic Variants ◽  
Method Analysis ◽  
Kyrgyz Population

Цель исследования - оценить вклад полиморфных вариантов g.15661G> T (ген ADIPOQ), p.A222V (ген MTHFR), p.Q192R (ген PON1), p.K23E (ген KCNJ11), g.53341C>T (ген TCF7L2), p.V109D (ген ITLN1) и p.P12A (ген PPARG) в развитие ожирения для лиц кыргызской национальности. Исследование было проведено по типу «случай-контроль» и включало 130 пациентов с ожирением (мужчин - 65 (50,0%), женщин - 65 (50,0%)). Группа сравнения - 115 человек без ожирения, метаболических нарушений и сердечно-сосудистых заболеваний в анамнезе (мужчин - 62 (53,9%), женщин - 53 (46,1%). Генотипирование осуществляли методом ПЦР-ПДРФ. Анализ межгенных взаимодействий проводился с использованием программы MDR 3.0.2. Маркерами развития ожирения в кыргызской популяции являются аллель V и генотип VV локуса p.A222V (MTHFR), а также аллель K и генотип KK локуса p.K23E (KCNJ11). При наличии генетического профиля AV (p.A222V, MTHFR) / EK (p.K23E, KCNJ11) вероятность развития ожирения возрастает более чем в 3 раза, ОШ=3,49, 95% ДИ=[1,44-8,45], p=0,001. In this study, we investigated whether polymorphisms g.15661G>T (ADIPOQ), p.A222V (MTHFR), p.Q192R (PON1), p.K23E (KCNJ11), g.53341C>T (TCF7L2), p.V109D (ITLN1) and p.P12A (PPARG) are associated with obesity in the Kyrgyz population. We genotyped 245 nonrelated adults Kyrgyz individuals. 130 patients (male - 65 (50,0%), female - 65 (50,0%) with obesity and 115 non-obese control subjects (male - 62 (53,9%), female - 53 (46,1%). Genotyping of single-nucleotide polymorphism was performed by PCR-RFLP method. Analysis of intergenic interactions conducted with MDR v.3.0.2 program. Тhe V allele and the VV genotype of the p.A222V locus (MTHFR), as well as the K allele and the KK genotype of the p.K23E locus (KCNJ11) increase risk of obesity in the Kyrgyz population. Subjects having the VV genotype of p.A222V locus (MTHFR) and KK genotype of the p.K23E locus (KCNJ11) had 3-fold [OR = 3,49 (1,44-8,45); p = 0,001] higher risk of developing compared with subjects carrying neither of these genotypes.

scholarly journals miR-608 rs4919510 C>G POLYMORPHISM DECREASED THE RISK OF BREAST CANCER IN AN IRANIAN SUBPOPULATION

2016 ◽  
Vol 38 (1) ◽  
pp. 57-59 ◽  
Author(s):  
M Hashemi ◽  
S Sanaei ◽  
M Rezaei ◽  
G Bahari ◽  
S M Hashemi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Large Scale ◽  
Target Genes ◽  
Clinicopathological Characteristics ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Small Noncoding Rnas ◽  
Pcr Rflp ◽  
Mirnas Expression ◽  
The Impact

Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on breast cancer (BC) risk. Materials and Me thods: This case-control study conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of miR608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Our findings showed that GC genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.28–0.88, p = 0.018) compared to CC genotype. Furthermore the G allele decreased the risk of BC (OR = 0.53, 95%CI 0.30–0.92, p = 0.024). No significant association was found between miR-609 genotypes and clinicopathological characteristics of BC patients (p > 0.05). Conclusion: Our findings indicate that miR-608 polymorphism might be associated with decreased risk of BC in an Iranian subpopulation. Further large-scale studies with different ethnicities are needed to verify our findings.

An association of the MCP-1 and CCR2 single nucleotide polymorphisms with colorectal cancer prevalence

2017 ◽  
Vol 89 (5) ◽  
pp. 1-5 ◽  
Author(s):  
Anna Walczak ◽  
Karolina Przybyłowska-Sygut ◽  
Andrzej Sygut ◽  
Adrianna Cieślak ◽  
Michał Mik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fragment Length Polymorphism ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Cancer Prevalence ◽  
Pcr Rflp ◽  
Study Support ◽  
Polymorphic Variants ◽  
Polymerase Chain

The aim of the study: We evaluated the connection between the presence of the -2518 A/G MCP-1 as well as 190 G/A CCR2 polymorphic variants and colorectal cancer (CRC) occurrence. Material and methods: Study group consisted of subjects with different stages of CRC as well as healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: W observed an association between the colorectal cancer and the GG genotype of the -2518 A/G MCP-1 single nucleotide polymorphism. No statistically significant correlation was found between CRC and the 190 G/A CCR2 polymorphism. Conclusion: The results of this study support the hypothesis that polymorphism in the MCP-1 gene may contribute to the etiology of colorectal cancer.

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

СONTRIBUTION OF POLYMORPHIC VARIATION OF ТP53 AND XRCC1 GENES TO THE SUSCEPTIBILITY TO BREAST CANCER FOR WOMEN OF KYRGYZ AND BELARUSIAN NATIONALITY - A COMPARATIVE STUDY ON MULTIFACTOR DIMENSIONALITY REDUCTION METHODS

2018 ◽  
Vol 64 (1) ◽  
pp. 95-101
Author(s):  
Nazira Aldasheva ◽  
Vyacheslav Kipen ◽  
Zhaynagul Isakova ◽  
Sergey Melnov ◽  
Raisa Smolyakova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Rflp Analysis ◽  
Kyrgyz Republic ◽  
Increased Risk ◽  
Polymorphic Variants ◽  
The Republic

Basing on Multifactor Dimensionality Reduction method we showed that polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) correlated with increased risk of breast cancer for women from the Kyrgyz Republic and the Republic of Belarus. Cohort for investigation included patients with clinically verified breast cancer: 117 women from the Kyrgyz Republic (nationality - Kyrgyz) and 169 - of the Republic of Belarus (nationality - Belarusians). Group for comparison included (healthy patients without history of cancer pathology at the time of blood sampling) 102 patients from the Kyrgyz Republic, 185 - from the Republic of Belarus. Respectively genotyping of polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) was done by PCR-RFLP. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Both ethnic groups showed an increase of breast cancer risk in the presence of alleles for SNPs Gln p.Q399R (XRCC1) in the heterozygous state: for the group “Kyrgyz” - OR=2,78 (95% CI=[1,60-4,82]), p=0,001; for the group “Belarusians” - OR=1,85 (95% СІ=[1Д1-2,82], p=0,004. Carriers with combination of alleles Gln (p.Q399R, XRCC1) and Pro (p.P72R, TP53) showed statistically significance increases of breast cancer risk as for patients from the Kyrgyz Republic (OR=2,89, 95% CI=[1,33-6,31]), so as for patients from the Republic of Belarus (OR=3,01, 95% CI=[0,79-11,56]).

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