Prognostic significance of P53 mutations in colon cancer at the population level
Prognostic significance of P53 mutations in colon cancer at the population level
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DOI：
10.1002/ijc.10405
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发表时间：
2002-06-01
影响因子：
6.4
通讯作者：
Slattery, ML
中科院分区：
文献类型：
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作者：
Samowitz, WS;Curtin, K;Slattery, ML
一些研究报道p53突变或某些类型的p53突变与结肠癌的不良预后相关，而其他研究未能证明这种关系。之前的这些研究都不是以人群为基础的。因此，我们在一项大型、基于人群的研究中评估了 p53 突变的预后意义，该研究对来自犹他州和加利福尼亚州的 1,464 名结肠癌患者进行了研究。通过 SSCP 分析检测外显子 5-8 的突变，然后对异常条带进行测序。在 1,464 名个体中的 665 名（45.4%）人的结肠癌中发现了 p53 突变。 p53 突变在远端肿瘤 (p < 0.01)、相对较高阶段的肿瘤 (p = 0.04)、无 MSI 的肿瘤 (p < 0.01) 和无 Ki-ras 突变的肿瘤 (p < 0.01) 中更为常见。在单变量分析中，p53 突变的肿瘤与野生型 p53 的肿瘤相比，其 5 年生存率显着较差（53.4% vs. 58.8%，p = 0.04）；错义突变、转换、颠换、影响p53分子结构的突变、β-夹心基序内的突变和近端肿瘤的突变也导致预后明显较差。然而，在多变量分析中，预后不良的唯一显着预测因子是 G245 热点突变（HRR = 2.16，95% CI 1.06-4.40）和近端肿瘤中的 p53 突变（HRR = 1.34，95% CI 1.07-1.63）。我们得出的结论是，总体 p53 突变状态并不是结肠癌预后不良的独立预测因子。然而，特定类别的突变，即 G245 热点突变和近端肿瘤突变，即使在调整年龄和分期后也与显着较差的生存率相关。 (C) 2002 Wiley-Liss, Inc.
Some studies have reported that p53 mutations or certain types of p53 mutation are associated with poor prognosis in colon cancer, while other studies have failed to show such a relationship. None of these previous studies was population-based. We therefore evaluated the prognostic significance of p53 mutations in a large, population-based study of 1,464 individuals with colon cancer from Utah and California. Mutations in exons 5-8 were detected by SSCP analysis, followed by sequencing of aberrant bands. p53 mutations were identified in colon cancers from 665 of 1,464 (45.4%) individuals. p53 mutations were significantly more common in distal tumors (p < 0.01), tumors of relatively high stage (p = 0.04), tumors without MSI (p < 0.01) and tumors without Ki-ras mutations (p < 0.01). In a univariate analysis, tumors with p53 mutations were associated with a significantly worse 5-year survival than those with wild-type p53 (53.4% vs. 58.8%, p = 0.04); significantly worse prognosis also was seen with missense mutations, transitions, transversions, mutations affecting the structure of the p53 molecule, mutations within the beta-sandwich motif and mutations in proximal tumors. In multivariate analyses, however, the only significant predictors of poor prognosis were G245 hot spot mutations (HRR = 2.16, 95% CI 1.06-4.40) and p53 mutations in proximal tumors (HRR = 1.34, 95% CI 1.07-1.63). We conclude that overall p53 mutational status is not an independent predictor of poor prognosis in colon cancer. However, specific classes of mutations, namely, the G245 hot spot mutation and mutations in proximal tumors, are related to significantly worse survival even after adjusting for age and stage. (C) 2002 Wiley-Liss, Inc.