Lasky T, Silbergeld E
Department of Epidemiology and Preventive Medicine, University of Maryland at Baltimore 21201-1596, USA.
Environ Health Perspect. 1996 Dec;104(12):1324-31. doi: 10.1289/ehp.961041324.
In this paper we describe a statistical analysis of the European Molecular Library p53 mutation database comparing p53 mutations occurring in breast, colorectal, liver, lung, and ovarian cancers. The analyses show that mutation hot spots vary by cancer and that base pair changes and predicted amino acid changes in the gene product vary by cancer and by codon. The analyses use relative frequencies and epidemiologic measures of effect (prevalence ratios) not applied previously to these data. The five cancers in the database with the largest sample sizes were breast (418), colorectal (398), liver (341), non-small cell lung (313), and ovarian cancers (251), for a total of 1,721 reports of p53 mutations. The five cancers varied considerably in the distribution of mutations over sites, with different hot spots in each cancer. At the six most frequently reported codon sites, we compared base pair and amino acid changes by type of cancer. The comparison of base pair changes indicated a predominance of particular base pair changes at a codon (for example, C-->T and G-->A changes at Codon 248) and their association with specific cancers (C-->T changes with colorectal cancer and G-->A changes with both colorectal and breast cancers at codon 248). Comparing predicted amino acid changes by codon and cancer was also intriguing, as in codons 175 and 273, where arginine to cysteine and arginine to histidine changes were frequent in breast, colorectal, and ovarian cancers. Variations in p53 mutational distributions by cancer may be explained by different exposures to carcinogens or by organ-specific clonal selection. Further research may be stimulated by this analysis.
在本文中，我们描述了对欧洲分子文库p53突变数据库的统计分析，该分析比较了乳腺癌、结直肠癌、肝癌、肺癌和卵巢癌中发生的p53突变。分析表明，突变热点因癌症类型而异，基因产物中的碱基对变化和预测的氨基酸变化也因癌症类型和密码子而异。这些分析使用了相对频率和效应的流行病学指标（患病率比），这些指标以前未应用于这些数据。数据库中样本量最大的五种癌症是乳腺癌（418例）、结直肠癌（398例）、肝癌（341例）、非小细胞肺癌（313例）和卵巢癌（251例），共有1721份p53突变报告。这五种癌症在突变位点的分布上有很大差异，每种癌症都有不同的热点。在六个最常报告的密码子位点，我们按癌症类型比较了碱基对和氨基酸变化。碱基对变化的比较表明，密码子处特定碱基对变化占主导（例如，密码子248处的C→T和G→A变化），以及它们与特定癌症的关联（密码子248处，C→T变化与结直肠癌相关，G→A变化与结直肠癌和乳腺癌均相关）。按密码子和癌症比较预测的氨基酸变化也很有趣，如在密码子175和273处，乳腺癌、结直肠癌和卵巢癌中精氨酸到半胱氨酸和精氨酸到组氨酸的变化很常见。p53突变分布因癌症而异，可能是由于致癌物暴露不同或器官特异性克隆选择所致。该分析可能会激发进一步的研究。
