ASO：IGF1基因SNP状态与前列腺癌高风险相关

胰岛素样生长因子-1 (IGF1)通路在病情恶化过程中起到了一个关键性的作用，流行病学研究同样证明，IGF1通路基因的单核苷酸多态性(SNP)与前列腺癌风险有关。然而在前列腺癌侵袭性及根治性前列腺切除术(RP)预后方面，此类SNP的临床意义尚未得到确定。

为此我国台湾中国医药大学的张绮芬(Chi-Fen Chang)博士等人进行了一项研究，该研究首次针对IGF1通路基因SNP对PSA复发的影响进行了评价。这项研究结果发表于2013年2月10日在线出版的《外科肿瘤学年鉴》(Annals of Surgical Oncology)杂志上。

该项研究的研究对象为320例接受RP治疗的局限性前列腺癌患者，研究人员对该患者队列中IGF1与IGF1R基因常见的4类SNP与确诊时年龄、术前前列腺特异性抗体(PSA)水平、Gleason病理评分、病理分期、手术切缘、淋巴结转移情况及PSA复发等因素间的关系进行了评价。同时通过Cox比例风险模型对PSA复发时间的预后意义进行了评价。

研究人员发现，IGF1 rs2946834等位基因/基因型以及IGF1基因中存在的一类特异的AT单体(含次级等位基因rs2946834)，与1.49- 2.22倍的晚期前列腺癌较高风险有关(P ≤ 0.028)。此外，包括IGF1 rs2946834 及IGF1R rs2016347在内的遗传相互作用与PSA复发存在显著关联(P = 0.033)。研究人员最终认为，IGF1 rs2946834及IGF1R rs2016347可能为根治性前列腺切除术预后的预测因素。

原文链接：

---

Common Variants in IGF1 Pathway Genes and Clinical Outcomes After Radical Prostatectomy


Abstract
Background
Insulin-like growth factor-1 (IGF1) pathway plays a critical role in malignant transformation, and epidemiology studies have also shown that single nucleotide polymorphisms (SNPs) in IGF1 pathway genes are associated with prostate cancer risk. However, the clinical significance of these SNPs on prostate cancer aggressiveness and prognosis after radical prostatectomy (RP) has not been determined.
Methods
We evaluated the associations of 4 common SNPs in IGF1 and IGF1R with age at diagnosis, preoperative prostate-specific antigen (PSA) level, pathologic Gleason score, pathologic stage, surgical margin, lymph node metastasis, and PSA recurrence in a cohort of 320 localized prostate cancer patients receiving RP. The prognostic significance on time to PSA recurrence was also assessed by Cox proportional hazards model.
Results
IGF1 rs2946834 alleles/genotypes and an IGF1 specific haplotype AT, containing the minor allele of rs2946834, were associated (P ≤ 0.028) with a 1.49- to 2.22-fold higher risk of having advanced-stage prostate cancer. In addition, a genetic interaction profile consisting of IGF1 rs2946834 and IGF1R rs2016347 was significantly associated with PSA recurrence (P = 0.033).
Conclusions
Our study is the first to evaluate the impact of SNPs in IGF1 pathway genes on PSA recurrence. A genetic interaction between IGF1 rs2946834 and IGF1R rs2016347 might be a predictor of outcomes following RP.

来源：丁香园