Al-Ghafari Ayat B, Al Qahtani Areej M, Alturki Suzan N, Al Doghaither Huda A, Elmorsy Ekramy M, Tashkandi Hanaa M, Abusanad Atlal M, Alkhayyat Shadi S, Omar Ulfat M, Zeeneldin Ahmed A
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Kingdom of Saudi Arabia.
Unit of Experimental Biochemistry, Faculty of Science, King Fahd Medical Research Center, Jeddah 21589, Kingdom of Saudi Arabia.
Oncol Lett. 2020 Nov;20(5):155. doi: 10.3892/ol.2020.12016. Epub 2020 Aug 24.
Multidrug resistance member 1 (MDR1) is located on chromosome 7 and encodes P-glycoprotein, which is universally accepted as a drug resistance biomarker. polymorphisms can alter protein expression or function, which has been previously reported to associate with various types of malignancies, such as colorectal cancer (CRC). Therefore, the present study aimed to determine the effects of polymorphisms on drug responses of Saudi patients with CRC. DNA samples were obtained from 62 patients with CRC and 100 healthy controls. Genotypes and allele frequencies of single nucleotide polymorphisms (SNPs) G2677T and T1236C were determined using the PCR-restriction fragment length polymorphism procedure. The results showed no significant differences in the genotype distribution and allele frequency of T1236C between patients with CRC and controls. However, G2677T was found to serve a highly significant role in protecting against the progression of CRC. In addition, none of the genotypes in SNPs T1236C and G2677T was found to affect chemoresistance to XELIRI and XELOX. In conclusion, although T1236C in the gene is not associated with CRC risk, G2677T protects against the development of CRC. Neither of the SNPs tested were associated with the risk of chemoresistance. Therefore, these two SNPs cannot be used as molecular markers for predicting drug response in patients with CRC.
多药耐药蛋白1（MDR1）位于7号染色体上，编码P-糖蛋白，它被广泛认为是一种耐药生物标志物。多态性可改变蛋白质表达或功能，此前已有报道称其与多种类型的恶性肿瘤相关，如结直肠癌（CRC）。因此，本研究旨在确定多态性对沙特CRC患者药物反应的影响。从62例CRC患者和100例健康对照中获取DNA样本。使用聚合酶链反应-限制性片段长度多态性方法测定单核苷酸多态性（SNP）G2677T和T1236C的基因型和等位基因频率。结果显示，CRC患者与对照组之间T1236C的基因型分布和等位基因频率无显著差异。然而，发现G2677T在预防CRC进展中起高度显著作用。此外，未发现SNP T1236C和G2677T中的任何基因型影响对XELIRI和XELOX的化疗耐药性。总之，尽管该基因中的T1236C与CRC风险无关，但G2677T可预防CRC的发生。所检测的两个SNP均与化疗耐药风险无关。因此，这两个SNP不能用作预测CRC患者药物反应的分子标志物。
