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 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.

• Authors: Tatiana Vidaurre, Sandro Casavilca, Paola Montenegro, Henry Gomez, Mónica Calderón, Jeannie Navarro, Jessica Aramburu, Ebert Poquioma, Yasuo Tsuchiya, Takao Asai, Yoichi Ajioka, Ayako Sato, Toshikazu Ikoma, Kazutoshi Nakamura
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 20 Issue 1 Pg. 289-294 (Jan 25 2019) ISSN: 2476-762X [Electronic] Thailand
• PMID: 30678452 (Publication Type: Journal Article)
• Copyright: Creative Commons Attribution License

Chemical References

• KRAS protein, human
• MAS1 protein, human
• Proto-Oncogene Mas
• TP53 protein, human
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins p21(ras)

Topics

• Adult
• Aged
• Aged, 80 and over
• Bolivia
• Exons (genetics)
• Female
• Gallbladder Neoplasms (genetics)
• Humans
• Male
• Middle Aged
• Mutation (genetics)
• Peru
• Proto-Oncogene Mas
• Proto-Oncogene Proteins p21(ras) (genetics)
• Tumor Suppressor Protein p53 (genetics)