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Document Type |
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Thesis |
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Document Title |
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GENETIC VARIANTS OF THE DRUG RESISTANCE (ABCB1) GENE AND THE RISK OF CHEMORESISTANCE IN COLORECTAL CANCER التغيرات الوراثية في جين (ABCB1) المقاوم للعقاقير وخطورة مقاومة العلاج الكيميائي في سرطان القولون والمستقيم |
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Subject |
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Faculty of Sciences |
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Document Language |
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Arabic |
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Abstract |
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ABCB1 gene, also known as multidrug resistance member 1 (MDR1), is located on chromosome 7 and encodes a P-glycoprotein (Pgp) that is universally accepted as a drug resistance biomarker. ABCB1 polymorphisms may either change its protein expression or alter its function, suggesting its possible association with cancers including colorectal cancer (CRC). Therefore, this study aimed to determine the genotypes distribution and alleles frequency of four major ABCB1 polymorphisms namely (T129C, C3435T, G2677T, and T1236C) in Saudi CRC patients. Then, these genetic results were correlated with CRC development and drug resistance. To the best of our knowledge, this study is the first study that performed on patients with CRC in Saudi Arabia. DNA samples were obtained from 62 CRC patients and 100 healthy controls. The frequencies of the genotypes and alleles of the four SNPs were determined by PCR-RFLP technique. All statistical correlations were performed by Chi-square test (P values <0.05 were considered statistically significant). The results showed that there was no significant difference (P>0.05) in genotypes distributions and allele frequencies of C3435T, T1236C, and T129C between CRC patients and controls. However, we found that SNP G2677T play a highly significant protection against the development of CRC particularly when the heterozygous (GT) and homozygous (TT) genotypes were compared with normal (GG) genotype. Moreover, the results showed that none of the genotypes in the (T1236C, G2677T, and C3435T) SNPs in ABCB1 gene can increase the risk of developing chemo-resistance to the currently used drugs such as Xeliri and Xelox. In conclusion, the results of the current study showed no association between SNPs T129C, C3435T and T1236C in ABCB1 drug resistant gene and the risk of CRC development except for the SNP G2677T that play a highly significant protection against the development of CRC in our population. Moreover, we also determined a non-significant association between these SNPs with the risk of chemo-resistance. Further examinations using larger number of samples and tissues are necessary to confirm our findings with more reliable conclusions. |
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Supervisor |
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Dr. Ayat Bader Al-Gafari |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1439 AH
2018 AD |
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Added Date |
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Thursday, June 7, 2018 |
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Researchers
| أريج مسفر القحطاني | Al-Qahtani, Areej Mesfer | Researcher | Master | |
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