Document Type: Research Articles
Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
Division of Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, Niigata, Japan.
Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Faculty of Health and Medical Sciences, Hokuriku University, Kanazawa, Ishikawa, Japan.
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.