Hebbar Mohamed, Adenis Antoine, Révillion Françoise, Duhamel Alain, Romano Olivier, Truant Stéphanie, Libersa Christian, Giraud Claire, Triboulet Jean-Pierre, Pruvot François-René, Peyrat Jean-Philippe
Department of Medical Oncology, University Hospital, Lille, France.
Eur J Cancer. 2009 Jul;45(10):1871-6. doi: 10.1016/j.ejca.2009.03.011. Epub 2009 Apr 8.
Some host-related factors may predict the risk of metastasis after surgery of colorectal cancer (CRC). The endothelial adhesion molecule E-selectin is implicated in the metastatic spread of CRC. We postulated that some polymorphisms within the E-selectin gene, especially the S128R polymorphism, may increase the risk of metastases by facilitating adhesion of tumour cells to the endothelium. We collected blood samples for DNA extraction from 264 patients treated for stage II or III CRC and from 310 healthy controls in order to assess three polymorphisms within the E-selectin gene (S128R, G98T and L554F) and one within the P-selectin gene (V640L). Genotypes were analysed by the allelic discrimination TaqMan real-time PCR assay. The S128R polymorphism was detected in 59 patients (22.3%) and was strictly correlated with the G98T polymorphism. In multivariate analysis, the S128R polymorphism was associated with shorter event-free survival (EFS) and overall survival (OS) in the whole population (EFS: P=.003, HR 1.82, 95% CI 1.23-2.70; OS: P<10(-4), HR 4.31, 95% CI 2.46-10.99), in patients with stage II CRC(EFS: P=.04, HR 1.92, 95% CI 1.02-3.60; OS: P=.02, HR 4.44, 95% CI 1.16-17.03), and in patients with stage III CRC (EFS: P=.04, HR 1.68, 95% CI 1.01-2.80; OS: P=.001, HR 4.04, 95% CI 1.73-9.46). L554F and V640L polymorphisms had no prognostic value. The S128R polymorphism is a constitutional factor associated with a higher risk of relapse and death in patients treated for CRC. This polymorphism detection may permit better selection of patients suitable for adjuvant therapy, especially among those with stage II disease.
一些与宿主相关的因素可能预测结直肠癌（CRC）手术后转移的风险。内皮黏附分子E-选择素与CRC的转移扩散有关。我们推测E-选择素基因内的一些多态性，尤其是S128R多态性，可能通过促进肿瘤细胞与内皮的黏附而增加转移风险。我们收集了264例接受II期或III期CRC治疗的患者以及310例健康对照的血样用于DNA提取，以评估E-选择素基因内的三种多态性（S128R、G98T和L554F）以及P-选择素基因内的一种多态性（V640L）。通过等位基因鉴别TaqMan实时PCR分析对基因型进行分析。59例患者（22.3%）检测到S128R多态性，且与G98T多态性密切相关。在多变量分析中，S128R多态性与整个人群较短的无事件生存期（EFS）和总生存期（OS）相关（EFS：P = 0.003，HR 1.82，95% CI 1.23 - 2.70；OS：P < 10⁻⁴，HR 4.31，95% CI 2.46 - 10.99），在II期CRC患者中（EFS：P = 0.04，HR 1.92，95% CI 1.02 - 3.60；OS：P = 0.02，HR 4.44，95% CI 1.16 - 17.03），以及在III期CRC患者中（EFS：P = 0.04，HR 1.68，95% CI 1.01 - 2.80；OS：P = 0.001，HR 4.04，95% CI 1.73 - 9.46）。L554F和V640L多态性无预后价值。S128R多态性是CRC治疗患者复发和死亡风险较高的一个体质因素。这种多态性检测可能有助于更好地选择适合辅助治疗的患者，尤其是II期疾病患者。
