Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 22252, Saudi Arabia.
Curr Oncol. 2023 Aug 30;30(9):8039-8053. doi: 10.3390/curroncol30090583.
We assess the contributions of genetic variants for the enzymes involved in capecitabine metabolism to colorectal cancer (CRC) development risk. In this case-control study, DNA samples were collected from 66 patients (King Abdulaziz University Hospital) and 65 controls (King Fahad General Hospital) between April and November 2022 to be used in PCR-RFLP. The chi-square (χ) test at a significance level of ˂ 0.05 was used to estimate genotype and allele frequencies. The Lys27Gln variant of cytidine deaminase (CDA) showed a risk ratio (RR) of 1.47 for heterozygous (AC) carriers, with genotype distributions for patients (χ = 1.97) and controls (χ = 14.7). Homozygous (AA) Ala70Thr carriers demonstrated a three-fold higher risk, with genotype distributions for patients (χ = 3.85) and controls (χ = 4.23). Genotype distributions of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T variant for patients were (χ = 22.43) and for controls were (χ = 0.07); for the A1298C variant, they were (χ = 54.44) for patients and (χ = 4.58) for controls. Heterozygous (AC) carriers of the A1298C variant demonstrated highly significant protection against CRC development (RR = 0.2, = 0.001), while a two-fold higher risk for CRC was estimated for homozygous genotype (CC) carriers. In conclusion, the heterozygous genotype of Lys27Gln, the homozygous genotype of Ala70Thr, and the homozygous genotype of A1298C were associated with CRC development risk. The heterozygous genotype of A1298C variant provided highly significant protection against CRC development. Further examinations using a larger population size are needed to reliably confirm our findings.
我们评估了参与卡培他滨代谢的酶的遗传变异对结直肠癌（CRC）发展风险的贡献。在这项病例对照研究中，于 2022 年 4 月至 11 月期间从 66 名患者（阿卜杜勒阿齐兹国王大学医院）和 65 名对照（法赫德国王综合医院）收集 DNA 样本，用于 PCR-RFLP。使用卡方检验（ ˂ 0.05）来估计基因型和等位基因频率。胞苷脱氨酶（CDA）的 Lys27Gln 变体的杂合（AC）携带者的风险比（RR）为 1.47，患者的基因型分布（ = 1.97）和对照组（ = 14.7）。Ala70Thr 纯合（AA）携带者的风险增加了三倍，患者的基因型分布（ = 3.85）和对照组（ = 4.23）。5,10-亚甲基四氢叶酸还原酶（MTHFR）C677T 变体的患者基因型分布为（ = 22.43），对照组为（ = 0.07）；对于 A1298C 变体，患者为（ = 54.44），对照组为（ = 4.58）。A1298C 变体的杂合（AC）携带者对 CRC 发展具有高度显著的保护作用（RR = 0.2， = 0.001），而纯合基因型（CC）携带者的 CRC 风险估计增加了两倍。总之，Lys27Gln 的杂合基因型、Ala70Thr 的纯合基因型和 A1298C 的纯合基因型与 CRC 发展风险相关。A1298C 变体的杂合基因型对 CRC 发展具有高度显著的保护作用。需要使用更大的人群规模进行进一步检查，以可靠地证实我们的发现。
