转移性结直肠癌患者在接受氟尿嘧啶和奥沙利铂治疗时的性别特异性基因组分析。
Gender-specific genomic profiling in metastatic colorectal cancer patients treated with 5-fluorouracil and oxaliplatin.
机构信息
Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
出版信息
Pharmacogenomics. 2011 Jan;12(1):27-39. doi: 10.2217/pgs.10.163.
AIMS
Survival and response rates in metastatic colorectal cancer remain poor, despite advances in drug development. There is increasing evidence to suggest that gender-specific differences may contribute to poor clinical outcome. We tested the hypothesis that genomic profiling of metastatic colorectal cancer is dependent on gender.
MATERIALS & METHODS: A total of 152 patients with metastatic colorectal cancer who were treated with oxaliplatin and continuous infusion 5-fluorouracil were genotyped for 21 polymorphisms in 13 cancer-related genes by PCR. Classification and regression tree analysis tested for gender-related association of polymorphisms with overall survival, progression-free survival and tumor response.
RESULTS
Classification and regression tree analysis of all polymorphisms, age and race resulted in gender-specific predictors of overall survival, progression-free survival and tumor response. Polymorphisms in the following genes were associated with gender-specific clinical outcome: estrogen receptor β, EGF receptor, xeroderma pigmentosum group D, voltage-gated sodium channel and phospholipase A2.
CONCLUSION
Genetic profiling to predict the clinical outcome of patients with metastatic colorectal cancer may depend on gender.
目的
尽管药物研发取得了进展，但转移性结直肠癌的生存率和缓解率仍然很差。越来越多的证据表明，性别特异性差异可能导致临床结局不佳。我们检验了这样一个假设，即转移性结直肠癌的基因组分析依赖于性别。
材料与方法
对 152 名接受奥沙利铂和持续输注氟尿嘧啶治疗的转移性结直肠癌患者进行了基因分型，共涉及 13 个癌症相关基因中的 21 个多态性，方法为 PCR。分类回归树分析检测了多态性与总生存期、无进展生存期和肿瘤反应之间的性别相关性。
结果
所有多态性、年龄和种族的分类回归树分析导致了总生存期、无进展生存期和肿瘤反应的性别特异性预测因子。以下基因中的多态性与性别特异性临床结局相关：雌激素受体 β、表皮生长因子受体、着色性干皮病组 D、电压门控钠通道和磷脂酶 A2。
结论
预测转移性结直肠癌患者临床结局的基因分析可能依赖于性别。
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