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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,SNP,Saudi Arabia,MAPK,pathway
- چکیده:
- چکیده انگلیسی: Background: Genetic mutations and polymorphisms play an important role in the transformation of primary cells to malignant cells as it may lead to disturbance of vital pathways regulating cell cycle, DNA damage repair, and apoptosis. In this study, we genotyped single nucleotide polymorphisms (SNPs) which were predicted to affect certain pathways and to increase the risk of breast cancer. Methods: The study included 81 Saudi breast cancer patients and 100 matching healthy controls from the Eastern Province in Saudi Arabia. The following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) were then genotyped by TaqMan genotyping assay and the allele and genotype distribution was compared. Results: The minor allele frequency of the following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) was T=0.17, A=0.28, A=0.22, and G=0.16 respectively. The G allele of the SNP rs3168891 was significantly associated with increased breast cancer risk (P = 0.00001) while the T allele of the same locus was associated with reduced risk of breast cancer in both heterozygous and homozygous states. The T allele of SNP rs2229714 which is located in the RPS6KA1 gene was also significantly associated with the increased risk of breast cancer. However, the rs2899849 SNP located in the Integrin beta-1 (ITGB1) gene was not associated with the increased risk of breast cancer in our study population. Haplotype analysis revealed the presence of three risk haplotypes that increases the risk of breast cancer (TGGT, TGTA, GATA). Conclusion: We showed that three, previously untested, SNPs are associated with increased risk of breast cancer in our population. This may be added to the list of factors involved in breast cancer risk assessment studies. The benefit and the utility of the in-silico prediction of disease risk factors and their genetic association had been demonstrated in this study, yet the predicted risk alleles have to be tested in clinical studies.
- انتشار مقاله: 20-02-1399
- نویسندگان: Ghadah Shareefi,Alaa Nabil Turkistani,Ahmed Alsayyah,Haitham Kussaibi,Maha Abdel Hadi,Khaled R Alkharsah
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: BRCA1 3’UTR variants rs8176318G/T,ER-Estrogen receptor,PR-Progesterone Receptor,Her2/neu
- چکیده:
- چکیده انگلیسی: Purpose: The impact of the BRCA1-3’UTR-variant on BRCA1 gene expression and altered responses to external
stimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in women
was also assessed but the conclusions were inconsistent. The present study concerns the relationship between the
BRCA1-3’UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of Saudi
Arabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls from
the northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3’UTR germline
variant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results:
The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% and
in healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to be
significantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32,
1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). There
were 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in our
cases. A significant correlation was also found between the BRCA1 3’UTR variants with the stage of the disease and
distant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the
3’untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breast
cancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studies
are needed to confirm this finding in other regions of Saudi Arabia.- انتشار مقاله: 15-09-1396
- نویسندگان: Rashid Mir,Jamsheed Javid,Ibrahim Abdullah Al Balawi,Khaled R Alkharsah,Maha Abdel Hadi,Mostafa Abdel Rahman,Ebtesam Hamoud,Yousef Al Alawi,Attiya Bin Mohammad Al Zahrani,F M Abu-Duhier
- مشاهده