Soliman Amr S, Bondy Melissa, Webb Charity Renee, Schottenfeld David, Bonner Joseph, El-Ghawalby Nabih, Soultan Ahmed, Abdel-Wahab Mohamed, Fathy Omar, Ebidi Gamal, Zhang Qing, Greenson Joel K, Abbruzzese James L, Hamilton Stanley R
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Int J Cancer. 2006 Sep 15;119(6):1455-61. doi: 10.1002/ijc.21986.
Variations in genetic mutations in pancreatic carcinoma between different populations have not been studied extensively, especially in developing countries where pancreatic cancer is rare. We studied the molecular pathology of 44 pancreatic carcinomas from patients residing in a heavily polluted region in the Nile River delta and compared the findings with tumors from 44 United States (US) patients. We evaluated K-ras mutations in codon 12, p53 mutations in exons 5-8, and Gadd45a mutations in exons 1 and 4. Overall, rates of K-ras, p53 and Gadd45 mutations were not statistically different in tumors of patients from Egypt and the US (67.4 vs. 63.4%; 27.3 vs. 36.4% and 9.1 vs. 4.5%, respectively). However, there were distinct differences in the specific types of K-ras and p53 mutations between the 2 groups. In K-ras, G --> T transversion mutation was more frequent in the tumors from Egypt than from the US (58.6 vs. 26.9%), whereas G --> C transversion was detected in 26.9% of US tumors but none from Egypt (p = 0.003). We also found a trend toward differences in the p53 exons in which mutations occurred, with higher frequency of exon 5 mutation and lower frequency of exon 6 mutation in Egyptian tumors. Logistic regression showed that K-ras G --> T transversion mutations and p53 exon 6 mutations were predicted by the country of residence of the patients. Our study identifies that there are differences in the types of mutations found in tumors from pancreatic carcinoma patients in Egypt and the US, and suggests that environmental factors may explain these differences.
不同人群胰腺癌基因突变的差异尚未得到广泛研究，尤其是在胰腺癌罕见的发展中国家。我们研究了居住在尼罗河三角洲重度污染地区的44例胰腺癌患者的分子病理学，并将结果与44例美国患者的肿瘤进行了比较。我们评估了密码子12处的K-ras突变、外显子5-8处的p53突变以及外显子1和4处的Gadd45a突变。总体而言，埃及和美国患者肿瘤中K-ras、p53和Gadd45突变的发生率在统计学上没有差异（分别为67.4%对63.4%；27.3%对36.4%和9.1%对4.5%）。然而，两组之间K-ras和p53突变的具体类型存在明显差异。在K-ras中，埃及肿瘤中G→T颠换突变比美国肿瘤更常见（58.6%对26.9%），而26.9%的美国肿瘤检测到G→C颠换，埃及肿瘤中未检测到（p = 0.003）。我们还发现突变发生的p53外显子存在差异趋势，埃及肿瘤中外显子5突变频率较高，外显子6突变频率较低。逻辑回归显示，K-ras G→T颠换突变和p53外显子6突变可由患者的居住国预测。我们的研究表明，埃及和美国胰腺癌患者肿瘤中发现的突变类型存在差异，并表明环境因素可能解释这些差异。
