Personalized and Precision Medicine Journal

Abstract Background:Breast cancer is one of the leading causes of cancer-related mortality among women worldwide. Germline mutations in the *BRCA1* gene and polymorphisms in the *TNF-α* gene have been implicated in breast cancer susceptibility. This study aimed to investigate the frequency of the *BRCA1* 185delAG and 5382insC mutations and their association with the *TNF-α* -308 G>A polymorphism for the early diagnosis of breast cancer in Iranian women.
Methods: A total of 84 archival breast tissue samples were collected from breast cancer patients treated at Khatam and Imam Khomeini hospitals. Genomic DNA was extracted using standard protocols. The *BRCA1* 185delAG and 5382insC mutations were analyzed by multiplex polymerase chain reaction (PCR), while the *TNF-α* -308 G>A polymorphism was determined using amplification refractory mutation system PCR (ARMS-PCR). Histopathological characteristics, including mitotic activity, necrosis, cellular pleomorphism, tumor grade, and the expression of ER, PR, and p53, were evaluated using standard histopathological and immunohistochemical methods. Statistical analysis was performed using the chi-square test in Epi Info version 7, with a significance level of *P* < 0.05.
Results: Among the 84 patients, 38 had a positive family history of breast cancer and 46 had no family history. In patients with a positive family history, three cases carried the *BRCA1* 5382insC mutation and two carried the 185delAG mutation, whereas only one 5382insC mutation was detected in patients without a family history. The distribution of *TNF-α* -308 genotypes (AA, AG, and GG) was 8, 14, and 16 cases, respectively, among patients with a family history, compared with 25, 12, and 9 cases in those without a family history. Conclusion: The findings suggest that the *BRCA1* 185delAG and 5382insC mutations, together with the *TNF-α* -308 GG genotype and clinicopathological characteristics, may serve as useful molecular markers for identifying women at increased risk of breast cancer. Their combined assessment may improve the early diagnosis and facilitate timely therapeutic intervention in Iranian women.

Abstract Mitochondria are the extra-nuclear source of DNA in cells and play an important role in cell death susceptibility,  oxidative stress regulation, metabolism, and signaling in normal cells. Because of this, its dysfunction can contribute to the progression of cancer and metastasis. Also, mtDNA mutations have been reported in many cancers, followed by altered mitochondrial activity and cellular signaling . This increase in mtDNA mutation is due to the proximity of the genome to the OXPHOS system which are thought to be more in extent than mutation nuclear. These mutations do not inactivate energy metabolism but change its state. Therefore, it is not surprising that the function of mitochondria is vital for cancer cells, in addition to understanding the mechanisms of mitochondrial function in the process of tumor formation and cancer progression is essential for cancer treatments.

Abstract Warning of the World Health Organization (WHO) indicates that novel coronavirus (COVID-19) is pandemic and causes global concern. COVID-19 has acute respiratory symptoms which leads to die in many cases through the world. We have found seven variants in 300 patients based on Next Generation Sequencing (NGS) which are related to infectious disease. According to the databases, we confirmed that rs2660 and rs1800450 have association with COVID-19 in the Iranian population.

Abstract Diabetes mellitus (DM) is a major public health issue in worldwide. Type 2 diabetes does not have a clear pattern of inheritance, although many affected individuals have at least one close family member, such as a parent or sibling, with the disease. The KCNJ11 gene is a member of the potassium channel gene family. polymorphisms  in KCNJ11  result  in  neonatal  diabetes and congenital hyper-insulinaemia, wherein the E23K (rs5219) polymorphism is linked with diabetes susceptibility where the K allele plays an important role in insulin secretion. In this study, we evaluate the frequency of these polymorphisms in a Kurdish population of 85 with type 2 diabetes. E23K polymorphism of KCNJ11 gene was genotyped by PCR-RFLP method. heterozygous carriers for AG are more in non‑diabetic patients (P = 0.034).

Abstract Metachromatic leukodystrophyis a kind of lysosomal storage disorder caused by a deficiency in the ARSA enzyme, which is involved in the metabolism of membrane sulfatides into galactosylceramide. ARSA gene mutation analysis is likely to be in increasing demand for the accurate detection of heterozygous carriers and for prenatal diagnosis in families with a metachromatic leukodystrophy proband. This study examined the sequence of the ARSA gene in 7 patients with metachromatic leukodystrophy by exon Sanger sequencing. Eleven mutations were found in the ARSA gene. It was further found that five mutations were probably damaging to the protein activity with a high score and specificity. The results pave the way to a more effective method for career detection , genetic diagnosis, and the counseling of Iranian patients with MLD disorder.
 

Abstract Obesity and type 2 diabetes are two complex disorders with strong genetic backgrounds, and both disorders cause other diseases and increase mortality. FTO is a protein-coding gene located on the long arm of chromosome 16 and linked to type 2 diabetes and obesity. The current study investigated the relationship between the RS16953002 polymorphism gene and type 2 diabetes and obesity in a population from Tehran. The study population included 150 people with type 2 diabetes and 150 healthy individuals. Genotyping was performed by RFLP-PCR. The results indicated the presence of the GG allele in 81% of diabetic patients but in only64% of non-diabetic participants, which shows a statistically significant difference in this regard. Thus, the current study has shown the role of FTO gene polymorphisms in the pathogenesis of people with type 2 diabetes and obesity.

Abstract Colorectal cancer is the third most common cancer and the second leading cause of cancer deaths in the world. Risk factors such as obesity, low-fiber diet, sedentary, and alcohol have been implicated in the development of this cancer. Cells have many mechanisms in place to fight malignancy and cancer, one of which is the detoxification system that protect the cell against DNA damage. One of the essential components of this system is the glutathione s-transferase. In this study, the genotype of region -69 promoter of this gene in 150 colorectal cancer patients and 150 healthy people was investigated by the RFLP method. T/T genotype is significantly associated with colorectal cancer (P = 0.0001), C/T genotype did not show a significant association with colorectal cancer and its frequency was not significantly different in both healthy and patient groups (P = 0.074), Most genotypes in the two groups were homozygous C / C and did not show a significant association with colorectal cancer.

Abstract In recent decades, there has been an increase in the incidence of cancer in the affected communities. However, the growth of therapeutic strategies has been very slow. Conventional diagnosis and subsequent treatment in medical centers originated from pathological based examinations, symptoms, and medications.