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

Abstract

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