Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Prevalence of Aflatoxin Induced p53 Mutation at Codon 249 (R249s) in Hepatocellular Carcinoma Patients with and without Hepatitis B Surface Antigen (HBsAg)

  • Published : 2013.12.31
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Abstract

Background: A missense mutation in exon 7 (R249S) of the p53 tumor suppressor gene is characteristic of aflatoxin B1 (AFB1) exposure. AFB1 is believed to have a synergistic effect on hepatitis virus B (HBV) carcinogenesis. However, results of studies comparing R249S prevalence among patients are conflicting. The aim of this study was to determine the prevalence of the R249S mutation in hepatocellular carcinoma (HCC) patients with or without positive HBsAg. Materials and Methods: Paraffin embedded liver tissues were obtained from 124 HCC patients who underwent liver resection and liver biopsy in King Chulalongkorn Memorial Hospital. Restriction fragment length polymorphism (RFLP) was utilized to detect the R249S mutation. Positive results were confirmed by direct sequencing. Results: Sixty four (52%) patients were positive for HBsAg and 18 (15%) were anti-HCV positive. 12 specimens tested positive by RFLP. Ten HCC patients (8.1%) were confirmed to be R249S positive by Sanger sequencing (AGG to AGT). Out of these 10, six were HBsAg positive, and out of the remaining 4, two were anti-HCV positive. The R249S prevalence among HCC patients with positive HBsAg was 9.4% compared to 6.7% for HBsAg negative samples. Patients with the R249S mutation were younger ($55{\pm}10$ vs $60{\pm}13$ year-old) and tended to have a more advanced Edmonson-Steiner grade of HCC, although differences did not reach statistical significance. Conclusions: Our study shows moderate prevalence of aflatoxin B1-related p53 mutation (R249S) in HCC with or without HBsAg. HBsAg positive status was not associated with R249S prevalence.

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References

  1. Behn M, Qun S, Pankow W, Havemann K, Schuermann M (1998). Frequent detection of ras and p53 mutations in brush cytology samples from lung cancer patients by a restriction fragment length polymorphism-based “enriched PCR” technique. Clin Cancer Res, 4, 361-71.
  2. Besaratinia A, Kim SI, Hainaut P, Pfeifer GP (2009). In vitro recapitulating of TP53 mutagenesis in hepatocellular carcinoma associated with dietary aflatoxin B1 exposure. Gastroenterol, 137, 1127-37. https://doi.org/10.1053/j.gastro.2009.06.002
  3. Bressac B, Kew M, Wands J, Ozturk M (1991) Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature, 350, 429-31. https://doi.org/10.1038/350429a0
  4. Bridges JF, Joy SM, Gallego G, et al (2011). Needs for hepatocellular carcinoma control policy in the Asia-Pacific region. Asian Pac J Cancer Prev, 12, 2585-91.
  5. Buetow KH, Sheffield VC, Zhu M, et al (1992). Low frequency of p53 mutations observed in a diverse collection of primary hepatocellular carcinomas. Proc Natl Acad Sci USA, 89, 9622-6. https://doi.org/10.1073/pnas.89.20.9622
  6. Cuny M, Kramar A, Courjal F, et al (2000). Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations. Cancer Res, 60, 1077-83.
  7. Dupont WD, Plummer WD (1990). Power and sample size calculations. A review and computer program. Control Clin Trials, 11, 116-28. https://doi.org/10.1016/0197-2456(90)90005-M
  8. El-Kafrawy SA, Abdel-Hamid M, El-Daly M, et al (2005). P53 mutations in hepatocellular carcinoma patients in Egypt. Int J Hyg Environ Health, 208, 263-70. https://doi.org/10.1016/j.ijheh.2005.02.002
  9. El-Serag HB, Rudolph KL (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterol, 132, 2557-76. https://doi.org/10.1053/j.gastro.2007.04.061
  10. Gouas DA, Shi H, Hautefeuille AH, et al (2010). Effects of the TP53 p.R249S mutant on proliferation and clonogenic properties in human hepatocellular carcinoma cell lines: interaction with hepatitis B virus X protein. Carcinogenesis, 31, 1475-82. https://doi.org/10.1093/carcin/bgq118
  11. Hamid AS, Tesfamariam IG, Zhang Y, Zhang ZG, (2013). Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention. Oncol Lett, 5, 1087-92. https://doi.org/10.3892/ol.2013.1169
  12. Hoque A, Patt YZ, Yoffe B, et al (1999). Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States? Nutr Cancer, 35, 27-33. https://doi.org/10.1207/S1532791427-33
  13. Hsu IC, Metcalf RA, Sun T, et al (1991). Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature, 350, 427-8. https://doi.org/10.1038/350427a0
  14. Jiang W, Wang XW, Unger T, et al (2010). Cooperation of tumor-derived HBx mutants and p53-249(ser) mutant in regulating cell proliferation, anchorage-independent growth and aneuploidy in a telomerase-immortalized normal human hepatocyte-derived cell line. Int J Cancer, 127, 1011-20.
  15. Khlangwiset P, Wu F (2010). Costs and efficacy of public health interventions to reduce aflatoxin-induced human disease. Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 27, 998-1014. https://doi.org/10.1080/19440041003677475
  16. Kirk GD, Lesi OA, Mendy M, et al (2005). 249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene, 24, 5858-67. https://doi.org/10.1038/sj.onc.1208732
  17. Liu Y, Wu F (2010). Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect, 118, 818-24. https://doi.org/10.1289/ehp.0901388
  18. Nogueira JA, Ono-Nita SK, Nita ME, et al (2009). 249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients. BMC cancer, 9, 204. https://doi.org/10.1186/1471-2407-9-204
  19. O'Brien A, Williams R (2008). Nutrition in end-stage liver disease: principles and practice. Gastroenterol, 134, 1729-40. https://doi.org/10.1053/j.gastro.2008.02.001
  20. Ortiz-Cuaran S, Villar S, Gouas D, et al (2013). Association between HBX status, aflatoxin-induced R249S TP53 mutation and risk of hepatocellular carcinoma in a casecontrol study from Thailand. Cancer Lett, 331, 46-51. https://doi.org/10.1016/j.canlet.2012.11.012
  21. Poovorawan Y, Chongsrisawat V, Theamboonlers A, et al (2012). Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. Hum Vaccin Immunother, 8, 896-904. https://doi.org/10.4161/hv.19989
  22. Qian GS, Kuang SY, He X, Groopman JD, Jackson PE (2002). Sensitivity of electrospray ionization mass spectrometry detection of codon 249 mutations in the p53 gene compared with RFLP. Cancer Epidemiol Biomarkers Prev, 11, 1126-9.
  23. Qu JH, Zhu MH, Lin J, et al (2005). Effects of hepatitis B virus on p53 expression in hepatoma cell line SMMU-7721. World J Gastroenterol, 11, 6212-5. https://doi.org/10.3748/wjg.v11.i39.6212
  24. Ross RK, Yuan JM, Yu MC, et al (1992). Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet, 339, 943-6. https://doi.org/10.1016/0140-6736(92)91528-G
  25. Smela ME, Hamm ML, Henderson PT, et al (2002). The aflatoxin B(1) formamidopyrimidine adduct plays a major role in causing the types of mutations observed in human hepatocellular carcinoma. Proc Natl Acad Sci USA, 99, 6655-60. https://doi.org/10.1073/pnas.102167699
  26. Soini Y, Chia SC, Bennett WP, et al (1996). An aflatoxinassociated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico. Carcinogenesis, 17, 1007-12. https://doi.org/10.1093/carcin/17.5.1007
  27. Sripathomswat N, Thasnakorn P (1981). Survey of aflatoxinproducing fungi in certain fermented foods and beverages in Thailand. Mycopathologia, 73, 83-8. https://doi.org/10.1007/BF00562595
  28. Srivatanakul P, Sriplung H, Deerasamee S, (2004). Epidemiology of liver cancer: an overview. Asian Pac J Cancer Prev, 5, 118-25.
  29. Stern MC, Umbach DM, Yu MC, et al (2001). Hepatitis B, aflatoxin B(1), and p53 codon 249 mutation in hepatocellular carcinomas from Guangxi, people's republic of China, and a meta-analysis of existing studies. Cancer Epidemiol Biomarkers Prev, 10, 617-25.
  30. Szymanska K, Lesi OA, Kirk GD, et al (2004). Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa. Int J Cancer, 1103, 374-9.
  31. Thongbai C, Sa-nguanmoo P, Kranokpiruk P, et al (2013). Hepatitis B virus genetic variation and TP53 R249S mutation in patients with hepatocellular carcinoma in Thailand. Asian Pac J Cancer Prev, 14, 3555-9. https://doi.org/10.7314/APJCP.2013.14.6.3555
  32. Villar S, Ortiz-Cuaran S, Abedi-Ardekani B, et al (2012). Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis, PloS One, 7, 37707.
  33. Volkmann M, Hofmann WJ, Muller M, et al (1994). p53 overexpression is frequent in European hepatocellular carcinoma and largely independent of the codon 249 hot spot mutation. Oncogene, 9, 195-204.
  34. Waenlor W, Wiwanitkit V (2003). Aflatoxin contamination of food and food products in Thailand: an overview. Southeast Asian J Trop Med Public Health, 34, 184-90.
  35. Wang LY, Hatch M, Chen CJ, et al (1996). Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan. Int J Cancer, 67, 620-5. https://doi.org/10.1002/(SICI)1097-0215(19960904)67:5<620::AID-IJC5>3.0.CO;2-W
  36. Wichajarn K, Kosalaraksa P, Wiangnon S (2008). Incidence of hepatocellular carcinoma in children in Khon Kaen before and after national hepatitis B vaccine program. Asian Pac J Cancer Prev, 9, 507-9.
  37. Williams JH, Phillips TD, Jolly PE, et al (2004). Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr, 80, 1106-22. https://doi.org/10.1093/ajcn/80.5.1106
  38. Wu HC, Wang Q, Yang HI, et al (2009). Aflatoxin B1 exposure, hepatitis B virus infection, and hepatocellular carcinoma in Taiwan. Cancer Epidemiol Biomarkers Prev, 18, 846-53. https://doi.org/10.1158/1055-9965.EPI-08-0697
  39. Yang M, Zhou H, Kong RY, et al (1997). Mutations at codon 249 of p53 gene in human hepatocellular carcinomas from Tongan, China. Mutat Res, 381, 25-9. https://doi.org/10.1016/S0027-5107(97)00142-5
  40. Yoo KY (2010). Cancer prevention in the Asia Pacific region. Asian Pac J Cancer Prev, 11, 839-844.

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