2025 年第 7 期 第 20 卷

二氢嘧啶脱氢酶基因多态性与晚期结直肠癌患者临床病理特征和化疗毒副作用及疗效的相关性分析

Analysis of the correlation between dihydropyrimidine dehydrogenase gene polymorphism and clinicopathological features, toxicity and efficacy of chemotherapy in patients with advanced colorectal cancer

作者：王福花1王馨焱2王春艳1刘娟3刘晓玲3

英文作者：Wang Fuhua1 Wang Xinyan2 Wang Chunyan1 Liu Juan3 Liu Xiaoling3

单位：1山西省肿瘤医院中国医学科学院肿瘤医院山西医院山西医科大学附属肿瘤医院检验科，太原030013；2山西医科大学第一临床医学院，太原030001；3山西省肿瘤医院中国医学科学院肿瘤医院山西医院山西医科大学附属肿瘤医院特需医疗部，太原030013

英文单位：1Department of Clinical Laboratory Shanxi Cancer Hospital Cancer Hospital Affiliated to Shanxi Medical University Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences Taiyuan 030013 China; 2First Clinical Medicine College of Shanxi Medical University Taiyuan 030001 China; 3Department of VIP Medical Services Shanxi Cancer Hospital Cancer Hospital Affiliated to Shanxi Medical University Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences Taiyuan 030013 China

关键词：结直肠癌；二氢嘧啶脱氢酶；基因多态性；化疗敏感性；无进展生存期

英文关键词：Colorectalcancer;Dihydropyrimidinedehydrogenase;Genepolymorphism;Chemotherapysensitivity;Progression-freesurvival

• 摘要：

• 目的 探讨二氢嘧啶脱氢酶（DPYD）基因多态性与晚期结直肠癌患者的临床病理特征、化疗毒副作用及疗效的相关性。方法 选取2020年4月1日至2021年4月1日山西省肿瘤医院消化内科收治的晚期结直肠癌一线治疗患者84例。对患者DPYD基因进行单核苷酸多态性分型，比较不同基因型患者临床病理特征、化疗毒副作用及疗效的差异。结果 84例结直肠癌患者中DPYD A1627G野生型AA者58例（69.0%），纯合突变型GG者2例（2.4%），杂合突变型AG者24例（28.6%）。结直肠癌患者DPYD基因状态与性别、年龄、肿瘤部位、组织学分级、转移部位等均无显著相关性（均P＞0.05）。DPYD基因状态与≥3级消化道反应和≥3级骨髓抑制有显著相关性（均P＜0.05）。不同基因型患者化疗敏感性比较，差异有统计学意义（χ2=4.719，P=0.046）。DPYD AA型患者无进展生存期（PFS）约10.0个月，长于AG型的6.4个月和GG型的5.5个月（χ2=6.130，P=0.047）。多因素分析显示，DPYD基因多态性（风险比=2.740，95%置信区间：1.444～5.199，P=0.002）和组织学分级（风险比=2.393，95%置信区间：1.196～4.785，P=0.014）是影响结直肠癌患者PFS的独立危险因素。结论 结直肠癌患者DPYD基因状态与性别、年龄、肿瘤部位、组织学分级、转移部位等均无显著相关性，而与≥3级消化道反应和≥3级骨髓抑制有显著相关性。DPYD基因多态性状态与化疗敏感性之间有一定的关联。DPYD AA型患者有较长的PFS。DPYD基因多态性是PFS的独立危险因素。

• Objective  To investigate the correlation between dihydropyrimidine dehydrogenase(DPYD) gene polymorphism and clinicopathological features, toxicity and efficacy of chemotherapy in patients with advanced colorectal cancer. Methods A total of 84 patients with advanced colorectal cancer who were admitted to the Department of Gastroenterology, Shanxi Cancer Hospital from April 1, 2020 to April 1, 2021 were selected. The single nucleotide polymorphism of DPYD gene was genotyped, and the clinicopathological characteristics, toxicity and efficacy of chemotherapy were compared among patients with different genotypes.Results Among the 84 colorectal cancer patients, 58 cases (69.0%) had DPYD A1627G wild type AA, 2 cases (2.4%) had homozygous mutant GG, and 24 cases (28.6%) had heterozygous mutant AG. The DPYD gene status of colorectal cancer patients was not significantly correlated with gender, age, tumor location, histological grade, and metastasis site (all P>0.05). The DPYD gene status was significantly correlated with ≥ 3 grade digestive tract reaction and ≥ 3 grade bone marrow suppression (both P<0.05). There was a significant difference in chemosensitivity between patients with different genotypes (χ2=4.719, P=0.046). The progression-free survival (PFS) of patients with DPYD AA was 10.0 months, which was longer than 6.4 months of AG and 5.5 months of GG (χ2=6.130, P=0.047). Multivariate analysis showed that, DPYD gene polymorphism (hazard ratio = 2.740, 95% confidence interval: 1.444-5.199, P=0.002) and histological grade (hazard ratio =2.393, 95% confidence interval: 1.196-4.785, P=0.014) were the independent risk factors for PFS of colorectal cancer patients. Conclusion The DPYD gene status of colorectal cancer patients was not significantly correlated with gender, age, tumor location, histological grade, and metastasis site, and was significantly correlated with ≥ 3 grade digestive tract reaction and ≥ 3 grade bone marrow suppression. There is a certain correlation between DPYD gene polymorphism and chemosensitivity. DPYD AA patients have longer PFS. DPYD gene polymorphism is an independent risk factor for PFS.