Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Cancer Prev Res (Phila). 2011 Feb;4(2):173-6. doi: 10.1158/1940-6207.CAPR-10-0386.
The study reported by Lee and colleagues in this issue of the journal (beginning on page 185) incorporated global genetic variation within a new assessment of the outcome of a previously reported phase-III trial of low-dose 13-cis-retinoic acid (13-cRA) for preventing second primary tumors (SPT) or the recurrence of head-and-neck cancer. This analysis identified genotypes of common single-nucleotide polymorphisms (SNP) and cumulative effect and potential gene-gene interactions that were highly associated with increased placebo-arm risk (prognostic) and/or with reduced treatment-arm risk and longer event-free survival (predictive). For example, the wild-type rs3118570 SNP of the retinoid X receptor alpha gene (carried by 71% of the 13-cRA trial population) marked a 3.33-fold increased SPT/recurrence risk in the placebo arm and a 38% reduced risk in the treatment arm. Adding two other informative genotypes strengthened the treatment-arm risk reduction to 76%, although the genotype trio reflected only 13% of the trial population. This report extends the concept of personalized therapy to cancer prevention.
李及其同事在本期杂志上报告的研究（从第 185 页开始）纳入了全球遗传变异，对先前报道的低剂量 13-顺式维甲酸（13-cRA）预防第二原发肿瘤（SPT）或头颈部癌症复发的 III 期试验结果进行了新的评估。这项分析确定了常见单核苷酸多态性（SNP）的基因型以及累积效应和潜在的基因-基因相互作用，这些与安慰剂组风险增加（预后）和/或治疗组风险降低以及无事件生存时间延长高度相关（预测）。例如，视黄醇 X 受体 α 基因的野生型 rs3118570 SNP（13-cRA 试验人群中有 71%携带）标志着安慰剂组 SPT/复发风险增加了 3.33 倍，而治疗组风险降低了 38%。添加另外两种信息基因型可使治疗组的风险降低进一步强化至 76%，尽管该基因型三联体仅反映了试验人群的 13%。该报告将个体化治疗的概念扩展到癌症预防领域。
