Differing molecular pathology of pancreatic adenocarcinoma in Egyptian and United States patients.
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.
Soliman
Amr S
AS
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. asoliman@umich.edu
Bondy
Melissa
M
Webb
Charity Renee
CR
Schottenfeld
David
D
Bonner
Joseph
J
El-Ghawalby
Nabih
N
Soultan
Ahmed
A
Abdel-Wahab
Mohamed
M
Fathy
Omar
O
Ebidi
Gamal
G
Zhang
Qing
Q
Greenson
Joel K
JK
Abbruzzese
James L
JL
Hamilton
Stanley R
SR
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004534:Egypt; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014481:United States; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins