Blanck H M, Tolbert P E, Hoppin J A
Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia 30322, USA.
Environ Mol Mutagen. 1999;33(2):111-22. doi: 10.1002/(sici)1098-2280(1999)33:2<111::aid-em3>3.0.co;2-f.
Both K-ras and p53 gene mutations are found commonly in pancreatic tumors. Analysis of the mutational patterns may provide insight into disease etiology. To further describe the mutational patterns of pancreatic cancer and to assess the evidence to date, we performed a pooled analysis of the published data on genetic mutations associated with pancreatic ductal adenocarcinoma. We included data from studies that evaluated point mutations in the two genes most studied in pancreatic cancer, K-ras and p53. A majority of the 204 tumors had mutations in at least one gene, with 29% having both K-ras and p53 mutations, 39% with K-ras mutation alone, and 16% having p53 mutation alone. Sixteen percent of tumors lacked mutation in either gene. K-ras mutations were present in high frequencies in all tumor grades (>69%). A statistically significant trend was observed for p53 mutation with higher tumor grade (P = 0.04). For K-ras, G2 and G3 grades, combined, had notably higher prevalences of mutation than G1 (P = 0.004). CGT mutations in K-ras codon 12 were marginally associated with lower tumor grade (P for trend = 0.09), and these tumors were somewhat less likely to have a p53 mutation than tumors with other K-ras mutations (P = 0.06). In the 59 K-ras+/p53+ tumors, 64% had the same type of mutation (transition or transversion) in both genes, suggesting a common mechanism. The mutational pattern of p53 in pancreatic cancer is similar to bladder cancer, another smoking-related cancer, but not to lung cancer. Analyses of molecular data, such as that performed here, present new avenues for epidemiologists in the study of the etiology of specific cancers.
K-ras和p53基因突变在胰腺肿瘤中均很常见。对突变模式的分析可能有助于深入了解疾病病因。为了进一步描述胰腺癌的突变模式并评估目前的证据，我们对已发表的与胰腺导管腺癌相关的基因突变数据进行了汇总分析。我们纳入了评估胰腺癌中研究最多的两个基因K-ras和p53点突变的研究数据。204个肿瘤中的大多数至少有一个基因发生突变，其中29%同时有K-ras和p53突变，39%仅有K-ras突变，16%仅有p53突变。16%的肿瘤两个基因均无突变。K-ras突变在所有肿瘤分级中均有较高频率出现（>69%）。观察到p53突变与较高肿瘤分级存在统计学显著趋势（P = 0.04）。对于K-ras，G2和G3级合并后的突变患病率明显高于G1级（P = 0.004）。K-ras密码子12的CGT突变与较低肿瘤分级存在微弱关联（趋势P = 0.09），与其他K-ras突变的肿瘤相比，这些肿瘤发生p53突变的可能性略低（P = 0.06）。在59个K-ras+/p53+肿瘤中，64%在两个基因中具有相同类型的突变（转换或颠换），提示存在共同机制。胰腺癌中p53的突变模式与另一种与吸烟相关的癌症——膀胱癌相似，但与肺癌不同。此类分子数据分析为流行病学家研究特定癌症的病因提供了新途径。
