Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution
Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution
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DOI：
10.1093/carcin/bgm138
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发表时间：
2007-08-01
期刊：
影响因子：
4.7
通讯作者：
Hamilton, Stanley R.
中科院分区：
文献类型：
--
作者：
Soliman, Amr S.;Lo, An-Chi;Hamilton, Stanley R.
背景资料：不同地理区域之间胰腺癌基因突变的变化尚未得到广泛研究，特别是在胰腺癌相对罕见的发展中国家。研究方法：我们研究了居住在尼罗河三角洲东部重污染地区的埃及患者的54例胰腺癌的分子病理学，并将研究结果与居住在低污染地区的45例患者的肿瘤进行了比较。结果如下：高污染地区患者肿瘤中K-ras第12位密码子突变率和p53第5-8外显子突变率均高于低污染地区患者（K-ras分别为61.5%和34.2%，P = 0.01; p53分别为25.9%和11.6%，P = 0.08）。K-ras和p53突变的具体类型在两个区域之间也有明显差异。高污染区的肿瘤中G → T k-ras颠换突变（密码子12）相对于野生型的比率（0.90）显著高于非污染区的肿瘤（0.28）（P = 0.03）。相对于野生型肿瘤，高污染区肿瘤中p53外显子5、7或8突变与野生型的比率显著高于非污染区的比率（0.28 vs 0.03，P = 0.01）。Logistic回归分析显示，K-ras基因G → T颠换突变与患者居住地区有关。结论：我们的研究表明，在埃及高污染和低污染地区胰腺癌患者中发现的K-ras和p53突变的频率和类型存在差异，并表明环境因素可能解释这些差异。我们推测胰腺癌发生中的基因-环境相互作用也发生在其他人群中。
Background: Variations in genetic mutations in pancreatic carcinoma between different geographical regions have not been studied extensively, especially in developing countries where pancreatic cancer is relatively rare. Methods: We studied the molecular pathology of 54 pancreatic adenocarcinomas from Egyptian patients residing in a heavily polluted region of the eastern Nile River delta and compared the findings with 45 tumors from patients residing in low-pollution regions. Results: Rates of K-ras mutation in codon 12 and of p53 mutation in exons 5-8 were higher in tumors of patients from the high-pollution region as compared with the low-pollution regions (61.5 versus 34.2%, respectively, for K-ras, P = 0.01; 25.9 versus 11.6%, respectively, for p53, P = 0.08). There were also distinct differences in the specific types of K-ras and p53 mutations between the two regions. The ratio of G-to-T k-ras transversion mutation (codon 12) relative to wild-type was significantly higher in tumors from the highpollution region (0.90) than tumors from the non-pollution site (0.28) (P = 0.03). Relative to tumors with wild-type, the ratio of p53 mutations in exons 5, 7 or 8 to wild-type in tumors from the high-pollution region was significantly higher than the ratio from the non-pollution site (0.28 versus 0.03, P = 0.01). Logistic regression showed that G-to-T transversion mutation in K-ras was predicted by the region of residence of the patients. Conclusions: Our study reveals that there are differences in the frequencies and types of K-ras and p53 mutations found in pancreatic adenocarcinomas of patients in high-poIlution and low-pollution regions in Egypt and suggests that environmental factors may explain these differences. We speculate that gene-environment interactions in pancreatic carcinogenesis also occur in other populations.