Soliman Amr S, Lo An-Chi, Banerjee Mousumi, El-Ghawalby Nabih, Khaled Hussein M, Bayoumi Sherif, Seifeldin Ibrahim A, Abdel-Aziz Atef, Abbruzzese James L, Greenson Joel K, Hamilton Stanley R
Department of Epidemiology, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, MI 48109, USA.
Carcinogenesis. 2007 Aug;28(8):1794-9. doi: 10.1093/carcin/bgm138. Epub 2007 Jun 16.
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.
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.
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 high-pollution 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.
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-pollution 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.
不同地理区域胰腺癌基因突变的差异尚未得到广泛研究，尤其是在胰腺癌相对罕见的发展中国家。
我们研究了居住在尼罗河三角洲东部污染严重地区的埃及患者的54例胰腺腺癌的分子病理学，并将结果与居住在低污染地区的45例患者的肿瘤进行了比较。
与低污染地区相比，高污染地区患者肿瘤中第12密码子K-ras突变率和第5-8外显子p53突变率更高（K-ras分别为61.5%对34.2%，P = 0.01；p53分别为25.9%对11.6%，P = 0.08）。两个区域K-ras和p53突变的具体类型也存在明显差异。高污染地区肿瘤中G-to-T k-ras颠换突变（第12密码子）相对于野生型的比例（0.90）显著高于无污染地区肿瘤（0.28）（P = 0.03）。相对于野生型肿瘤，高污染地区肿瘤中第5、7或8外显子p53突变与野生型的比例显著高于无污染地区（0.28对0.03，P = 0.01）。逻辑回归显示，K-ras中的G-to-T颠换突变可由患者居住区域预测。
我们的研究表明，埃及高污染和低污染地区患者胰腺腺癌中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过程中的基因-环境相互作用在其他人群中也会发生。
