Carcinogenesis Advance Access published online on June 16, 2007
Carcinogenesis, doi:10.1093/carcin/bgm138
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Differences in K-ras and P53 Gene Mutations among Pancreatic Adenocarcinomas Associated with Regional Environmental Pollution
1 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
2 Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
3 Gastrointestinal Surgery Center, Mansoura University, Mansoura, Egypt
4 National Cancer Institute of Cairo University, Cairo, Egypt
5 Tanta Cancer Center, Tanta, Egypt
6 South Valley Cancer Center, Assiut University, Assiut, Egypt
7 Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
8 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA
9 Department of Pathology and Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
* Author to whom all correspondence and reprint requests should be addressed at: Amr Soliman, M.D., Ph.D., Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory St., Ann Arbor, MI 48109. Telephone: (734) 764-5469; Fax: (734) 764-3192; email: asoliman{at}umich.edu
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% vs. 34.2%, respectively, for K-ras, P=0.01; 25.9% vs. 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 vs. 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.
Key Words: Pancreatic cancer • molecular pathology • K-ras • p53 • pollution • Egypt
Received April 20, 2007; revised June 5, 2007; accepted June 11, 2007.
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