Tumor Protein p53 and K-ras Gene Mutations in Peruvian Patients with Gallbladder Cancer

Document Type: Research Articles

Authors

1 Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.

2 Division of Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

3 Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, Niigata, Japan.

4 Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

5 Faculty of Health and Medical Sciences, Hokuriku University, Kanazawa, Ishikawa, Japan.

Abstract

Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographic
location on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factors
have not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patients
with gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a high
gallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissue
sections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection. Mutations in exons
5 to 8 of TP53 and codons 12, 13, and 61 of K-ras were examined using direct sequencing. Results: TP53 mutations
were observed in 10 (33.3%) of patients, but K-ras mutations were absent. Nine (90%) TP53 mutations were point
mutations (7 missense and 2 silent mutations), and the most frequent substitution was a G:C to A:T transition. G:C to
A:T transitions at the CpG site or G:C to T:A transversions were found in one patient each. No significant differences
were found in the frequency of TP53 and K-ras mutations among patients in the 5 countries. Conclusions: Our findings
suggest that endogenous mechanisms and exogenous carcinogens may affect the carcinogenic process in Peruvian
gallbladder cancer patients, similar to that in Bolivian patients. Further studies with a larger sample size are needed
to clarify these findings.

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