ABSTRACT
Background: Breast cancer (BC) is well-known as the most common malignancy and the first leading cause of cancer-related death among women worldwide. Evidence suggests that familial history and age are important risk factors for the development of this disease in Iran. Mutations in BRCA1 and BRCA2 genes are the cause of 5 to 10% of hereditary BC. Recent studies demonstrated that mutations in BRCA1 were observed in high-risk women with family histories of BC. However, to date, the mutations have not been elucidated in BC patients from east of Iran. The purpose of this study was to analyze BRCA1 mutations in BC patient from South Khorasan Province. Methods: In the present study, 88 BC patients (11 positive family history) were screened for mutations in BRCA1. The analysis of BRCA1 was carried out by SSCP (single-strand conformation polymorphism) for shorter exons and direct sequencing in the case of longer ones. Results: Twenty-eight of the patients (31.8%) had a synonymous mutation (c.4308T>C) in exon 13. A missense mutation (c. 4837A>G) was presented in exon 16 with a frequency of 56.8 %. In exon 11 three missense mutations were observed, and the frequency rate for c.3113A>G was 32.5%, for c.3119G>A was 5%, and the highest frequency belonged to c.3548A>G with 72.4% in familial BC and 45.4% in the non-familial group. Conclusion: In our study, five mutations were found, but none of the founder mutations were identified in this population. Two missense mutations in exon 16 (56.8%) and in exon 11 (65%) had the highest frequency in South Khorasan Province.
ABSTRACT
The genetic factors are determinants in required dosage changes of warfarin among which are polymorphisms of CYP2C9 and VKORC1 genes. The present study aimed to determine the allele and genotype frequency of CYP2C9 and VKORC1 genes in Birjand population. This study was conducted on 120 individuals who referred to Imam Reza and Vali-Asr hospitals for PT/INR test. After extracting the genomic DNA, the considered sequences were amplified by PCR, and restriction fragment length polymorphism analysis was done by AvaII and KpnI enzymes to determine allele polymorphisms. Moreover, related sequences of VKORC1, after amplification, were sequenced for determining the genotype. Allelic and genotypic frequencies as well as Hardy-Weinberg equilibrium, observed heterozygosity, expected heterozygosity, and polymorphism information content were calculated by PowerMarker V 3.25 software. Amongst 120 individuals in this study with the mean age of 58.12 ± 12.7 years, 80.8%, 9.1%, and 10% exhibited the alleles of 1, 2, and 3 CYP2C9 gene, respectively. The genotype frequencies of 1/1, 1/2, 2/2, 3/1, 3/2, and 3/3 of this gene were found to be 64.1, 15.8, 0, 17.5, 2.5, and 0 %, respectively. In -1639 G>A region, VKORC1 had normal homozygote genotype (GG) and in 1173 C>T region, heterozygote (CT) with the frequency of 48.7% and 45.9% had the most prevalence. Compared with other populations, there is a considerable difference between the allele frequency of CYP2C9 and VKORC1 genetic variance. Since 35.8% of the selected populations carry an abnormal allele causing sensitivity to warfarin, the specialists at medical centers must be informed about the genotypes of patients before prescribing warfarin.