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Pesticides induce oxidative DNA damage and genotoxic effects such as DNA single-strand breaks (SSBs), double-strand breaks (DSBs), DNA adducts, chromosomal aberrations, and enhanced sister chromatid exchanges. Such DNA damage can be repaired by DNA repair mechanisms. In humans, single nucleotide polymorphisms (SNPs) are present in DNA repair genes involved in base excision repair (BER) (OGG1, XRCC1, and APE1), nucleotide excision repair (NER) (XPC, XPD, XPF, XPG, and ERCC1), and double-strand break repair (DSBR) (XRCC4 and RAD51). This systematic review intends to provide information about occupational pesticide exposure, genotoxic effects of pesticides as well as association of DNA repair gene polymorphisms with the risk of pesticide-induced DNA damage. Polymorphisms present in DNA repair genes may influence interindividual variation in DNA repair capacity (DRC) by altering the functional properties of DNA repair enzymes and thus modulate DNA damage. The mechanisms of oxidative damage and disrupted DNA repair caused by the pesticides explain the link between pesticide exposure and adverse health outcomes. These polymorphisms in DNA repair genes could be used as biomarkers of susceptibility for pesticide-induced DNA damage among agricultural workers. It could also be useful as a preventive measure by identifying the genetic susceptibility of agricultural workers to pesticide-induced oxidative stress as well as pesticide poisoning. Keywords: Biomarkers, DNA damage, DNA repair, gene polymorphisms, pesticides, Author(s): Rupinder Kaur (corresponding author) [1]; Karashdeep Kaur [2] INTRODUCTION Pesticides are complex chemical substances used in agriculture to control pests and to fight plant diseases. These are nonbiodegradable, can [...]

Background Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome caused by pathogenic variants in the gene TP53. This gene codes for the P53 protein, a crucial player in genomic stability, which functions as a tumor suppressor gene. Individuals with LFS frequently develop multiple primary tumors at a young age, such as soft tissue sarcomas, breast cancer, and brain tumors. Case presentation A 38 years-old female with a history of femur osteosarcoma, ductal carcinoma of the breast, high-grade breast sarcoma, pleomorphic sarcoma of the left upper limb, infiltrating lobular carcinoma of the breast, gastric adenocarcinoma, leiomyosarcoma of the right upper limb, and high-grade pleomorphic renal sarcoma. Complete molecular sequencing of the TP53 gene showed c.586 C > T (p.R196X) in exon 6, which is a nonsense mutation that produces a shorter and malfunctioning P53. Family history includes advanced father's age at the time of conception (75 years), which has been associated with an increased risk of de novo germline mutations. The patient had seven paternal half-siblings with no cancer history. The patient received multiple treatments including surgery, systemic therapy, and radiotherapy, but died at the age of 38. Conclusions Advanced paternal age is a risk factor to consider when hereditary cancer syndrome is suspected. Early detection of hereditary cancer syndromes and their multi-disciplinary surveillance and treatment is important to improve clinical outcomes for these patients. Further investigation of the relationship between the pathogenic variant of TP53 and its phenotype may guide the stratification of surveillance and treatment. Keywords: Li Fraumeni syndrome, TP53, P53, De novo mutation, Advanced paternal age, Severe phenotype, Author(s): Juan Pablo Arango-Ibaéez[sup.1,2], Luis Gabriel Parra-Lara[sup.1,2], Ãngela R. Zambrano[sup.3] and Lisa Ximena Rodríguez-Rojas[sup.1,4] Background Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome with an autosomal dominant pattern of inheritance [...]

Background Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed. Results The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production. Conclusions Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure. Keywords: Helicobacter pylori, Whole genome sequencing, Virulence, Biofilm formation, Antibiotic resistance, Clarithromycin, Author(s): Naim Asyraf Rosli[sup.1], Anis Rageh Al-Maleki[sup.1,2], Mun Fai Loke[sup.3], Eng Guan Chua[sup.4], Mohammed Abdelfatah Alhoot[sup.5,6] and Jamuna Vadivelu[sup.7] Introduction Helicobacter pylori is a spiral-shaped Gram-negative bacteria that thrives in [...]

Background Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. Main body Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. Conclusion Universal screening could be an option to address the problem of underdiagnosis. Keywords: Lynch Syndrome, Clinical criteria, Genetics aspects, Amsterdam, Bethesda, Author(s): Miguel Angel Trujillo-Rojas[sup.1], María de la Luz Ayala-Madrigal[sup.2], Melva Gutiérrez-Angulo[sup.3], Anahí González-Mercado[sup.2] and José Miguel Moreno-Ortiz[sup.2] Introduction Lynch Syndrome (LS), previously known as hereditary non-polyposis colorectal cancer [1, 2], [...]

Byline: Amany. Mustafa, Ghada. Shams, Eman. Fawzy, Naglaa. Alhusseini, Rana. Khashaba, Ola. EL-Shimi Background: Apolipoprotein E (APOE) gene isoforms have been found to affect the risk of superficial fungal infections [...]