title: Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution.
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.
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, 109 Observatory Street, Ann Arbor, MI 48109, USA. asoliman@umich.edu
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
authors.forename: An-Chi
authors.initials: AC
authors.lastname: Lo
authors.forename: Mousumi
authors.initials: M
authors.lastname: Banerjee
authors.forename: Nabih
authors.initials: N
authors.lastname: El-Ghawalby
authors.forename: Hussein M
authors.initials: HM
authors.lastname: Khaled
authors.forename: Sherif
authors.initials: S
authors.lastname: Bayoumi
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Seifeldin
authors.forename: Atef
authors.initials: A
authors.lastname: Abdel-Aziz
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D004787:Environmental Pollution / Q000009:adverse effects; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000235:genetics*