Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution

Amr S. Soliman, An Chi Lo, Mousumi Banerjee, Nabih El-Ghawalby, Hussein M. Khaled, Sherif Bayoumi, Ibrahim A. Seifeldin, Atef Abdel-Aziz, James L. Abbruzzese, Joel K. Greenson, Stanley R. Hamilton

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Abstract

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 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. 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-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.

Original languageEnglish (US)
Pages (from-to)1794-1799
Number of pages6
JournalCarcinogenesis
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2007

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ASJC Scopus subject areas

  • Cancer Research

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Soliman, A. S., Lo, A. C., Banerjee, M., El-Ghawalby, N., Khaled, H. M., Bayoumi, S., Seifeldin, I. A., Abdel-Aziz, A., Abbruzzese, J. L., Greenson, J. K., & Hamilton, S. R. (2007). Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution. Carcinogenesis, 28(8), 1794-1799. https://doi.org/10.1093/carcin/bgm138