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.
Uvod: Mutacije u genu BRCA1 dovedene su u vezu s karcinomom jajnika i kod žena sa visokim rizikom može se vršiti testiranje BRCA. Ova studija osmišljena je s namerom da se odredi učestalost tri varijante polimorfizama pojedinačnih nukleotida (SNP) u genu BRCA1 i ekspresija BRCA1 kod Saudijki sa karcinomom jajnika.
Metode: Nivoi ekspresije mRNK gena BRCA1 proučavani su u 10 uzoraka tkiva s karcinomom jajnika i 10 zdravih tkiva jajnika pomoću kvantitativne reakcije lanca polimeraze u realnom vremenu (qPCR). Ova studija je takođe obuhvatila 28 žena koje su imale karcinom jajnika i bile uspešno operisane i 90 zdravih žena bez istorije karcinoma. Uzorci krvi uzeti su u EDTA epruvete i korišćeni za ekstrahovanje DNK. Genotipizacija je izvršena pomoću seta Taqman® SNP Genotyping putem RT-PCR. Varijante uključene u istragu bile su c.871 T>C (rs799917), c.1040 G>A (rs4986852), c.181 T>G (rs28897672) u genu BRCA1.
Rezultati: Varijanta c.181 T>G (rs28897672) pokazala je značajno različite učestalosti genotipova alela između pacijenata i kontrolnih subjekata (p = 0,002, odnosno 0,02).Genotip TG imao je značajnu protektivnu ulogu (OR = 0,36, p = 0,024). Pokazalo se da je ekspresija mRNK gena BRCA1 bila niska u tkivima s karcinomom jajnika.
Zaključak: Ova studija je pokazala da je c.181 T>G u genima BRCA1 povezan s razvojem karcinoma jajnika kod sau dijskih žena. Potrebne su nove studije kako bi se otkrilo koji bi još polimorfizmi (SNP) mogli biti povezani s karcinomom jajnika i kako bi se razumeli mehanizmi uključeni u smanje nje ekspresije gena BRCA1 u tkivima s karcinomom jajnika.
Keywords: BRCA1; Saudi Arabia; c.181 T>G; ovarian cancer; polymorphism.