DOI QR코드

DOI QR Code

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

  • Asai, Takao (Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare) ;
  • Loza, Ernesto (Bolivian Japanese Institute of Gastroenterology) ;
  • Roig, Guido Villa-Gomez (Bolivian Japanese Institute of Gastroenterology) ;
  • Ajioka, Yoichi (Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences) ;
  • Tsuchiya, Yasuo (Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare) ;
  • Yamamoto, Masaharu (Department of Health Nutrition, Niigata University of Health and Welfare) ;
  • Nakamura, Kazutoshi (Division of Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences)
  • Published : 2014.07.15

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.

Keywords

References

  1. Asai T, Tsuchiya Y, Okano K, et al (2012). Aflatoxin contamination of red chili pepper from Bolivia and Peru, countries with high gallbladder cancer incidence rates. Asian Pac J Cancer Prev, 13, 5167-70. https://doi.org/10.7314/APJCP.2012.13.10.5167
  2. Carriaga MT, Henson DE (1995). Liver, gallbladder, extrahepatic bile ducts and pancreas. Cancer, 75, 171-90. https://doi.org/10.1002/1097-0142(19950101)75:1+<171::AID-CNCR2820751306>3.0.CO;2-2
  3. Chhabra D, Oda K, Jagannath P, et al (2012). Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac J Cancer Prev, 13, 187-90. https://doi.org/10.7314/APJCP.2012.13.1.187
  4. Fujii K, Yokozaki H, Yasui W, et al (1996). High frequency of p53 gene mutation in adenocarcinomas of the gallbladder. Cancer Epidemiol Biomarkers Prev, 5, 461-6.
  5. Funabiki T, Matsubara T, Miyakawa S, Ishihara S (2009). Pancreaticobiliary maljunction and carcinogenesis to biliary and pancreatic malignancy. Langenbecks Arch Surg, 394, 159-69. https://doi.org/10.1007/s00423-008-0336-0
  6. Goldin RD, Roa JC (2009). Gallbladder cancer: a morphological and molecular update. Histopathology, 55, 218-29. https://doi.org/10.1111/j.1365-2559.2008.03192.x
  7. Greenblatt MS, Bennett WP, Hollstein M, Harris CC (1994). Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 54, 4855-78.
  8. Greene FL, Page DL, Fleming ID, et al (2002). American Joint Committee On Cancer Staging Manual, 6th edn (New York, Springer).
  9. Guo RS, Shi PD, Zhou J, Chen YY (2013). Somatostatin receptors 3, 4 and 5 play important roles in gallbladder cancer. Asian Pac J Cancer Prev, 14, 4071-5. https://doi.org/10.7314/APJCP.2013.14.7.4071
  10. Hanada K, Itoh M, Fujii K, et al (1996). K-ras and p53 mutations in stage I gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct. Cancer, 77, 452-8. https://doi.org/10.1002/(SICI)1097-0142(19960201)77:3<452::AID-CNCR5>3.0.CO;2-M
  11. Hanada K, Tsuchida A, Iwao T, et al (1999). Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct. Am J Gastroenterol, 94, 1638-42. https://doi.org/10.1111/j.1572-0241.1999.01155.x
  12. Harris CC (1996). The 1995 Walter hubert lecture--molecular epidemiology of human cancer: insights from the mutational analysis of the p53 tumour-suppressor gene. Br J Cancer, 73, 261-9. https://doi.org/10.1038/bjc.1996.47
  13. Hussain SP, Harris CC (2000). Molecular epidemiology and carcinogenesis: endogenous and exogenous carcinogens. Mutat Res, 462, 311-22. https://doi.org/10.1016/S1383-5742(00)00015-6
  14. Iwase T, Nakazawa S, Yamao K, et al (1997). Ras gene point mutations in gallbladder lesions associated with anomalous connection of pancreatobiliary ducts. Hepatogastroenterology, 44, 1457-62.
  15. Jones PA, Buckley JD, Henderson BE, Ross RK, Pike MC (1991). From gene to carcinogen: a rapidly evolving field in molecular epidemiology. Cancer Res, 51, 3617-20.
  16. Lazcano-Ponce EC, Miquel JF, Munoz N, et al (2001). Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin, 51, 349-64. https://doi.org/10.3322/canjclin.51.6.349
  17. Matsubara T, Sakurai Y, Sasayama Y, et al (1996). K-ras point mutations in cancerous and noncancerous biliary epithelium in patients with pancreaticobiliary maljunction. Cancer, 77, 1752-7. https://doi.org/10.1002/(SICI)1097-0142(19960415)77:8+<1752::AID-CNCR27>3.3.CO;2-0
  18. Misra S, Chaturvedi A, Misra NC, Sharma ID (2003). Carcinoma of the gallbladder. Lancet Oncol, 4, 167-76. https://doi.org/10.1016/S1470-2045(03)01021-0
  19. Moore SP, Forman D, Pineros M, et al (2014). Cancer in indigenous people in Latin America and the Caribbean: a review. Cancer Med, 3, 70-80. https://doi.org/10.1002/cam4.134
  20. Moreno M, Pimentel F, Gazdar AF, Wistuba Ii, Miquel JF (2005). TP53 abnormalities are frequent and early events in the sequential pathogenesis of gallbladder carcinoma. Ann Hepatol, 4, 192-9.
  21. Nagahashi M, Ajioka Y, Lang I, et al (2008). Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary. World J Gastroenterol, 14, 70-5. https://doi.org/10.3748/wjg.14.70
  22. Ozturk M (1991). p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet, 338, 1356-9. https://doi.org/10.1016/0140-6736(91)92236-U
  23. Rai R, Tewari M, Kumar M, Singh AK, Shukla HS (2011). p53: its alteration and gallbladder cancer. Eur J Cancer Prev, 20, 77-85. https://doi.org/10.1097/CEJ.0b013e328341e371
  24. Randi G, Franceschi S, La Vecchia C (2006). Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer, 118, 1591-602. https://doi.org/10.1002/ijc.21683
  25. Rideout WM, 3rd, Coetzee GA, Olumi AF, Jones PA (1990). 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science, 249, 1288-90. https://doi.org/10.1126/science.1697983
  26. Serra I, Yamamoto M, Calvo A, et al (2002). Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Int J Cancer, 102, 407-11. https://doi.org/10.1002/ijc.10716
  27. Srivastava V, Patel B, Kumar M, Shukla M, Pandey M (2013). Cyclin D1, retinoblastoma and p16 protein expression in carcinoma of the gallbladder. Asian Pac J Cancer Prev, 14, 2711-5. https://doi.org/10.7314/APJCP.2013.14.5.2711
  28. Takagi S, Naito E, Yamanouchi H, et al (1994). Mutation of the p53 gene in gallbladder cancer. Tohoku J Exp Med, 172, 283-9. https://doi.org/10.1620/tjem.172.283
  29. Taner CB, Nagorney DM, Donohue JH (2004). Surgical treatment of gallbladder cancer. J Gastrointest Surg, 8, 83-9. https://doi.org/10.1016/j.gassur.2003.09.022
  30. Tsuchiya Y, Terao M, Okano K, et al (2011). Mutagenicity and mutagens of the red chili pepper as gallbladder cancer risk factor in Chilean women. Asian Pac J Cancer Prev, 12, 471-6.
  31. Wistuba Ii, Gazdar AF (2004). Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer, 4, 695-706. https://doi.org/10.1038/nrc1429
  32. Wu Q, He XD, Yu L, Liu W, Tao LY (2012). The metabolic syndrome and risk factors for biliary tract cancer: a case-control study in China. Asian Pac J Cancer Prev, 13, 1963-9. https://doi.org/10.7314/APJCP.2012.13.5.1963
  33. Yokoyama N, Hitomi J, Watanabe H, et al (1998a). Mutations of p53 in gallbladder carcinomas in high-incidence areas of Japan and Chile. Cancer Epidemiol Biomarkers Prev, 7, 297-301.
  34. Yokoyama N, Watanabe H, Ajioka Y, et al (1998b). Genetic alterations in gallbladder carcinoma: a review. Nihon Geka Gakkai Zasshi, 99, 687-95.

Cited by

  1. 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 vol.16, pp.8, 2015, https://doi.org/10.7314/APJCP.2015.16.8.3505
  2. CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians vol.17, pp.2, 2016, https://doi.org/10.7314/APJCP.2016.17.2.781
  3. 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) vol.2017, pp.1607-8462, 2017, https://doi.org/10.1155/2017/1532835