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INTERNATIONAL CONGRESS OF

PharmacoGenetics

• Evaluation and bioinformatic analysis of the genetic origin of colorectal cancer patients and their response to new chemotherapy drugs

• Majid Mesgartehrani,^1,* Saba Ghoreishi,² Mohammad Mahdi Eslami,³ Saeid Mirlohi,⁴
  1. Iran Genomics Scientific Pole, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. Islamic Azad University of Urmia
  3. Tehran University of Medical Sciences, Tehran, Iran
  4. Tehran University of Medical Sciences, Tehran, Iran
  
  
  
• Introduction: CRC is the third most common cancer and the fourth leading cause of cancer-related deaths, with a higher incidence in Western countries. The probability of developing CRC is about 4%-5%. Risk factors include age, chronic disease history, lifestyle, and gut microbiota imbalances. CRC is caused by mutations in oncogenes, tumor suppressor genes, and DNA repair genes. It can be classified as sporadic (70%), inherited (5%), or familial (25%). Common symptoms include rectal bleeding, abdominal pain, changes in bowel habits (constipation or diarrhea), unexplained weight loss, and anemia. Rectal bleeding is the most frequently reported symptom. Pathogenic mechanisms include chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Key mutations affect pathways like WNT, MAPK/PI3K, TGF-β, and TP53. Treatment typically involves surgical resection followed by chemotherapy and targeted therapies (e.g., monoclonal antibodies against VEGF and EGFR). Alternative therapies are also being explored to enhance effectiveness and reduce side effects.
• Methods: One of the most reliable sources in this research is the NCBI database. The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). First, we found genes related to colorectal cancer through the NCBI site, and then entered the abbreviations of genes related to colorectal cancer from the SNP section of the same site in the search section. Then we analyzed the data related to polymorphisms and after preparing this information, we entered the MagaGene software. In the meta-analysis stage, we first entered the names of genes involved in colorectal cancer, phenotypes, alleles, and the number of population and citations of each gene. In the next step, the names of the drugs and the side effects of taking the drugs in colorectal cancer were investigated.
• Results: With the investigations carried out on the MegaGene site, we found out that among the 96 genes that play a role in the occurrence of colorectal cancer, three genes account for the highest percentage, which means that they have the highest polymorphism statistics. These 3 genes are: 1)CRP with 6 SNPs and 3.87% influence 2)TNF with 5 SNPs and 3.22% influence 3)IL10 with 4 SNPs and 2.58% influence
• Conclusion: By examining the effects and side effects of drugs in people with colorectal cancer despite the presence of polymorphisms in the genes involved in this disease, while examining 8 different drugs for the treatment of CRC, we found that patients should not use multiple drugs to treat their symptoms. These drugs include: 1) The side effect of Eloxatin for people with ABCC2 genetic background is diarrhea. 2) The side effect of A.S.A for people with MLH1 genetic background is nausea. 3) The side effect of Celebrex for people with MLH1 genetic background is nausea. 4) The side effect of Adrucil for people with MLH1 genetic background is nausea.
• Keywords: Key words:Colorectal cancer ,CRC symptoms, Polymorphism, Bioinformatics analysis, chemotherapy drug