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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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Soliman AS,Lo AC,Banerjee M,El-Ghawalby N,Khaled HM,Bayoumi S,Seifeldin IA,Abdel-Aziz A,Abbruzzese JL,Greenson JK,Hamilton SR

doi

10.1093/carcin/bgm138

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

1794-9

issue

eissn

0143-3334

issn

1460-2180

pii

bgm138

journal_volume

pub_type

杂志文章

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Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution.