PDF(Pubmed)
Abstract：
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 (χ2) test at a significance level of p ˂ 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 (χ2 = 1.97) and controls (χ2 = 14.7). Homozygous (AA) Ala70Thr carriers demonstrated a three-fold higher risk, with genotype distributions for patients (χ2 = 3.85) and controls (χ2 = 4.23). Genotype distributions of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T variant for patients were (χ2 = 22.43) and for controls were (χ2 = 0.07); for the MTHFR A1298C variant, they were (χ2 = 54.44) for patients and (χ2 = 4.58) for controls. Heterozygous (AC) carriers of the A1298C variant demonstrated highly significant protection against CRC development (RR = 0.2, p = 0.001), while a two-fold higher risk for CRC was estimated for homozygous genotype (CC) carriers. In conclusion, the heterozygous genotype of CDA Lys27Gln, the homozygous genotype of CDA Ala70Thr, and the homozygous genotype of MTHFR A1298C were associated with CRC development risk. The heterozygous genotype of MTHFR A1298C variant provided highly significant protection against CRC development. Further examinations using a larger population size are needed to reliably confirm our findings.
摘要：
我们评估了遗传变异对卡培他滨代谢酶对大肠癌（CRC）发展风险的贡献。在这项病例对照研究中，2022年4月至11月，从66名患者（阿卜杜勒阿齐兹国王大学医院）和65名对照（法赫德国王总医院）收集DNA样本，用于PCR-RFLP。在P=0.05的显著性水平下的卡方(χ2)检验用于估计基因型和等位基因频率。胞苷脱氨酶（CDA）的Lys27Gln变体显示杂合（AC）携带者的风险比（RR）为1.47，患者(χ2=1.97)和对照组(χ2=14.7)的基因型分布。纯合（AA）Ala70Thr携带者表现出三倍的风险，患者（χ2=3.85）和对照组（χ2=4.23）的基因型分布。患者的5,10-亚甲基四氢叶酸还原酶（MTHFR）C677T变体的基因型分布为（χ2=22.43），对照组为（χ2=0.07）；对于MTHFRA1298C变体，患者为（χ2=54.44），对照组为（χ2=4.58）。A1298C变体的杂合（AC）携带者表现出对CRC发展的高度显着的保护作用（RR=0.2，p=0.001），而估计纯合基因型（CC）携带者的CRC风险高2倍。总之,CDALys27Gln的杂合基因型，CDAAla70Thr的纯合基因型，MTHFRA1298C纯合基因型与CRC发生风险相关。MTHFRA1298C变体的杂合基因型提供了针对CRC发展的高度显著的保护。需要使用更大的人口规模进行进一步的检查，以可靠地确认我们的发现。
