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2019, vol. 38, iss. 1, pp. 13-21
Novel associations between BRCA1 variants c.181 t>g (rs28897672) and ovarian cancer risk in Saudi females
aKing Saud University, College of Science, Department of Biochemistry, Riyadh, Saudi Arabia
bKing Saud Bin Abdul Aziz University for Health Sciences, College of Science and Health Professions, Department of Basic Sciences, Riyadh, Saudi Arabia
cKing Saud University, College of Medicine, Department of Obs/Gyn, Riyadh, Saudi Arabia
dKing Saud University, College of Science, Department of Biochemistry, Genome Research Chair, Riyadh, Saudi Arabia
eKing Saud University, College of Medicine, Department of Pathology, Riyadh, Saudi Arabia
fKing Saud University, Center for Science and Medical Studies for Girls, Central Laboratory, Riyadh, Saudi Arabia
Keywords: ovarian cancer; BRCA1; polymorphism; Saudi Arabia; c.181 T> G
Background: Mutations in BRCA1 gene have been implicated in ovarian cancers, and BRCA testing may be conducted in high-risk women. This study was designed to determine the frequency of three single nucleotide polymorphisms (SNPs) variants in BRCA1 gene and BRCA1 expression in Saudi females with ovarian cancer. Methods: Expression levels of mRNA of BRCA1 gene were studied in 10 ovarian cancer and 10 normal ovarian tissues, by quantitative real time polymerase chain reaction (qPCR). The study also included 28 females who had suffered from ovarian cancer and had been successfully operated upon and 90 healthy females with no history of cancer. Blood was drawn in EDTA tubes and used for extraction of DNA. The genotyping was carried out using Taqman® SNP Genotyping kit by RT-PCR. The variants investigated included c.871 T> C (rs799917), c.1040 G > A (rs4986852), c.181 T> G (rs28897672) in BRCA1 gene. Results: The c.181 T> G (rs28897672) showed significantly different genotype and allele frequencies between the patients and the control subjects (p value = 0.002 and 0.02, respectively). The genotype TG was significantly protective (OR = 0.36, p value = 0.024). The mRNA expression of BRCA1 gene was found to be low in the ovarian cancer tissues. Conclusions: This study showed that c.181 T> G in BRCA1 genes is associated with the development of ovarian cancer in Saudis. More studies are needed to unveil other SNPs that may be associated with ovarian cancer and to understand the mechanism(s) involved in reducing the expression of BRCA1 gene in ovarian cancer tissues.
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article language: English
document type: Original Scientific Paper
PMC ID: PMC6298454
DOI: 10.2478/jomb-2018-0037
published in SCIndeks: 04/02/2020

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