مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Investigation of Common Polymorphisms in Melanoma Skin Cancer based on Gender in The Genetic Profile of The Iranian Population and Assessment of Chemotherapy Side Effects
Investigation of Common Polymorphisms in Melanoma Skin Cancer based on Gender in The Genetic Profile of The Iranian Population and Assessment of Chemotherapy Side Effects
Majid Mesgar Tehrani,1,*Ariana Esfahaian,2Mohammad Mehdi Eslami,3Reza Mirlohi,4
1. Member of the Core Committee of the National Genomics Hub, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2. Islamic Azad University, Tehran Central Branch 3. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran 4. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran
Introduction: Melanoma only accounts for about 2% of malignant skin cancer but causes most deaths. More than 2 million cases of skin cancer were diagnosed in the United States in 2010.
Over the past several decades, the incidence of melanoma has risen sharply worldwide, with the highest rates observed in fair-skinned populations, particularly in regions with intense ultraviolet (UV) radiation exposure such as Australia and New Zealand.
Melanoma is an aggressive malignant neoplasm derived from melanocytes. Melanocytes are found in the basal layer of the epidermis.
Environmental risk factors, especially chronic UV exposure, interact with host factors such as skin phenotype, genetic susceptibility, and immunologic status to drive melanoma development. On a molecular level, melanoma pathogenesis involves the accumulation of genetic mutations that activate oncogenes, inactivate tumor suppressor genes, and impair DNA repair mechanisms. This leads to uncontrolled melanocyte proliferation and tumor progression. Several genetic pathways are frequently disrupted in melanoma, including those involving the BRAF, NRAS, CDKN2A, and CDK4 genes, each of which contributes to dysregulation of the cell cycle, resistance to apoptosis, and enhanced tumor invasiveness. The identification of these mutations has significant implications for precision oncology, as it enables the design of targeted therapies and personalized treatment strategies aimed at improving patient outcomes while minimizing toxicity.
Methods: In this study, genetic data were obtained from the National Center for Biotechnology Information (NCBI) database, with a particular focus on the Single Nucleotide Polymorphism (SNP) section. Pharmacogenetic analysis was performed using the MegaGene software to evaluate polymorphism data and to identify genetically driven adverse drug reactions. This approach allowed for the assessment of patient-specific genetic variations that may influence both drug efficacy and toxicity profiles in melanoma treatment. The methodology integrated bioinformatic data retrieval with in silico pharmacogenetic modeling, providing a comprehensive framework for predicting drug–gene interactions in the context of melanoma therapy. Such an approach reflects the increasing importance of computational tools in oncology, enabling the translation of genomic information into clinically actionable insights.
The analysis identified CDK4 as one of the key genes implicated in melanoma, with common polymorphisms observed at RS11547328, RS2072052, and RS2069502. CDK4 plays a critical role in regulating the G1–S transition in the cell cycle, and mutations or polymorphisms within this gene can contribute to uncontrolled cellular proliferation. In addition to its pathogenic role, CDK4 is a potential therapeutic target, and several CDK4/6 inhibitors have been developed and tested for cancer treatment, including melanoma. However, the clinical application of these inhibitors is associated with potential adverse effects. CDK4 inhibitors used in cancer therapy may cause adverse effects, including gastrointestinal disturbances, hepatic dysfunction, hematologic abnormalities, and other treatment-related toxicities. Understanding the patient’s genetic background, particularly the presence of CDK4 polymorphisms, could therefore be critical for predicting the likelihood and severity of such side effects.
Results: This study emphasizes the necessity of pre-treatment genetic screening in melanoma patients. Prior to prescribing drugs and initiating therapy, genetic testing should be performed to detect polymorphisms in common genes such as BRAF, CDK4, and MC1R. If such polymorphisms are identified, treatment plans can be adjusted to incorporate alternative drugs or dosing regimens that are associated with fewer adverse effects. This patient-tailored approach is consistent with the principles of precision medicine, which aim to maximize therapeutic efficacy while minimizing harm. By integrating genomic profiling into routine clinical practice, oncologists can make more informed decisions regarding drug selection and therapy design.
The findings underscore the potential of pharmacogenetic analysis not only as a tool for understanding melanoma biology but also as a practical means of improving patient outcomes. As melanoma incidence continues to rise globally, particularly in populations with high UV exposure and genetic susceptibility, the integration of molecular diagnostics into treatment planning becomes increasingly vital. Advances in bioinformatics, genomic databases, and analytical software such as MegaGene have made it possible to perform such analyses efficiently and at relatively low cost.
Conclusion: In conclusion, melanoma remains a significant global health challenge due to its aggressive nature, rising incidence, and potential for rapid metastasis. The results of this study highlight the importance of integrating genomic data analysis into melanoma care and suggest that broader adoption of pharmacogenetic testing could significantly enhance the safety and efficacy of melanoma treatment strategies worldwide.