High Frequency of TP53 but not K-ras Gene Mutations in Bolivian Patients with Gallbladder Cancer

Abstract

Although genetic characteristics are considered to be a factor influencing the geographic variation in the prevalence of gallbladder cancer (GBC), they have not been well studied in Bolivia, which has a high prevalence rate of GBC. The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary. DNA was extracted from cancer sites in paraffin-embedded tissue from 36 patients using a microdissection technique. TP53 mutations at exons 5 to 8 and K-ras mutations at codons 12, 13 and 61 were examined using direct sequencing techniques. The data obtained were compared with those in the other high-GBC-prevalence countries. Of the 36 patients, 18 (50.0%) had a TP53 mutation (one mutation in each of 17 patients and three mutations in one patient), and only one (2.8%) had a K-ras mutation. Of the 20 TP53 mutations, 12 were of the transition type (60.0%). This rate was significantly lower than that in Chile (12/12, P<0.05). In addition, three mutations were of the CpG transition type (15.0%), which is a feature of endogenous mutation. All three were found in the hot spot region of the TP53 gene. In contrast, G:C to T:A transversion was found in Bolivia, suggesting the presence of exogenous carcinogens. Our findings suggest that the development of GBC in Bolivia is associated with both exogenous carcinogens and endogenous mechanisms. The identification of an environmental risk factor for GBC is needed to confirm these findings.

Gallbladder Carcinoma in the United States: A Population Based Clinical Outcomes Study Involving 22,343 Patients from the Surveillance, Epidemiology, and End Result Database (1973–2013)

“…Metaplasia most commonly arises due to inflammation caused by chronic gallstone irritation [14]. Inflammation then leads to increased expression of COX2 and inhibition of tumor suppressor genes such as p53 [14, 17, 18]. …”

High Frequency of Codon 12 but not Codon 13 and 61 K-ras Gene Mutations in Invasive Ductal Carcinoma of Breast in a South Indian Population

“…In this present study we did not found any mutation of codon 13 and 61 may be due to stage of disease as our sample consist of only stage II. Null association studies with K-RAS mutation were also reported by Mohammad et al (2013) Chronic Myloid Leukemia, Takao Asai et al (2014) in Gall bladder cancer.…”

Meta-signature of mutated genes in gallbladder cancer: evidence based high throughput screening assays

“…Cardesa et al (11) represented that TP53 gene mutations were observed in up to 50% of head and neck squamous-cell carcinomas and approximately 65% of them have aberrant expression of TP53. Szymańska et al (12) also reported that TP53 was the most frequently mutated gene in human cancer, such as hepatocellular carcinoma and oesophagus (13), exploredTP53 mutations in GBC patients, and found nearly half of GBC patients have TP53 mutations. In our meta-analysis, we also found that TP53 was the most recurrent mutated gene in GBC (crude P value =1.44×10 -6 , corrected P value =1.00×10 -3 , Table 2).…”