University of Liverpool, Liverpool, L69 3BX, UK; Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Wirral, CH63 4JY, UK.
University of Liverpool, Liverpool, L69 3BX, UK.
Crit Rev Oncol Hematol. 2017 Dec;120:127-140. doi: 10.1016/j.critrevonc.2017.09.009. Epub 2017 Sep 25.
Chemotherapy-induced peripheral neuropathy (CIPN) can adversely affect completion of systemic anti-cancer treatment and cause long-term morbidity. Increasingly pharmacogenetic studies have been performed to explore susceptibility to this important adverse effect. A systematic review was conducted to identify pharmacogenetic studies, assess their quality and findings and undertake meta-analysis where possible. 93 studies were included. Notable methodological issues included lack of standardisation and detail in phenotype definition and acknowledgement of potential confounding factors. Insufficient data was presented in many studies meaning only a minority could be included in meta-analysis showing mainly non-significant effects. Nonetheless, SNPs in CYP2C8, CYP3A4, ARHGEF10, EPHA and TUBB2A genes (taxanes), FARS2, ACYP2 and TAC1 (oxaliplatin), and CEP75 and CYP3A5 (vincristine) are of potential interest. These require exploration in large cohort studies with robust methodology and well-defined phenotypes. Seeking standardisation of phenotype, collaboration and subsequently, individual-patient-data meta-analysis may facilitate identifying contributory SNPs which could be combined in a polygenic risk score to predict those most at risk of CIPN.
化疗引起的周围神经病（CIPN）可影响全身抗癌治疗的完成，并导致长期发病。越来越多的药物遗传学研究已经进行，以探索对这种重要不良反应的易感性。进行了系统评价，以确定药物遗传学研究，评估其质量和结果，并在可能的情况下进行荟萃分析。共纳入 93 项研究。值得注意的方法学问题包括缺乏表型定义的标准化和详细信息，以及对潜在混杂因素的认识。许多研究提供的资料不足，这意味着只有少数研究可以进行荟萃分析，表明主要是非显著影响。尽管如此，CYP2C8、CYP3A4、ARHGEF10、EPHA 和 TUBB2A 基因（紫杉烷）、FARS2、ACYP2 和 TAC1（奥沙利铂）以及 CEP75 和 CYP3A5（长春新碱）中的 SNP 具有潜在的研究意义。这些需要在具有稳健方法和明确表型的大型队列研究中进行探索。寻求表型的标准化、合作以及随后的个体患者数据荟萃分析，可能有助于确定可能导致 CIPN 的贡献性 SNP，并可将其组合成多基因风险评分，以预测最易发生 CIPN 的人群。
