TY - JOUR
T1 - Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution
AU - Soliman, Amr S.
AU - Lo, An Chi
AU - Banerjee, Mousumi
AU - El-Ghawalby, Nabih
AU - Khaled, Hussein M.
AU - Bayoumi, Sherif
AU - Seifeldin, Ibrahim A.
AU - Abdel-Aziz, Atef
AU - Abbruzzese, James L.
AU - Greenson, Joel K.
AU - Hamilton, Stanley R.
N1 - Funding Information:
Eli Lilly Research, Topfer Research fund from M. D. Anderson Cancer Center and grants CA K07 090241, R03 CA099513-01, R03 CA 123715 and R25 112383 and Cancer Center Support Grants from the National Cancer Institute to the University of Michigan (5 P30 CA46592) and The University of Texas M. D. Anderson Cancer Center (P30 CA16672).
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgm138
DO - 10.1093/carcin/bgm138
M3 - Article
C2 - 17575320
AN - SCOPUS:34548106268
VL - 28
SP - 1794
EP - 1799
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 8
ER -