Carcinogenesis Advance Access originally published online on June 16, 2007
Carcinogenesis 2007 28(8):1794-1799; 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
Department of Epidemiology
1 Department of Biostatistics, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, MI 48109, USA
2 Gastrointestinal Surgery Center, Mansoura University, Mansoura 35516, Egypt
3 National Cancer Institute of Cairo University, Cairo 11796, Egypt
4 Tanta Cancer Center, Tanta 31512, Egypt
5 South Valley Cancer Center, Assiut University, Assiut 71526, Egypt
6 Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
7 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
8 Department of Pathology and Division of Pathology and Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
* To whom correspondence should be addressed. Tel: +1 734 764 5469; Fax: +1 734 764 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 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.
Received April 20, 2007; revised June 5, 2007; accepted June 11, 2007.