Association of N-acelyltransferase-2 Phenotype and CYP1A2 Activity with Cholangiocarcinoma in Thailand
Abstract
Background/Aims: Arylamine N-acetyltransferase-2 and cytochrome P450 1A2 have been implicated in the carcinogen activation and conferred cancer susceptibility. Present study was set to determine whether acetylation phenotype and P450 1A2 were associated with cholangiocarcinoma.
Materials and Methods: Ninety-six unrelated Thais were recruited for the study: 52 healthy controls and 44 cholangiocarcinoma patients. The acetylation phenotype was assessed and P450 1A2 activity was determined in vivo using the caffeine metabolic ratio (CMR) after oral administration of a cup of coffee.
Results: The caffeine metabolic ratio in the control and patient groups varied widely and the frequency distribution was apparently non-normal. The CMR value was higher in the controls particularly in non-smokers. Taken individually rapid acetylator status was not significantly associated with cholangiocarcinoma, however the joint effect of acetylation and P450 1A2 activity resulted in a presented risk of cancer, odds ratio=3.5 (95% confident interval, 1.0 to 12.1)
Conclusions: Arylamine N-acetyltransferase-2 and cytochrome P450 1A2 may play a role in presenting susceptibility to cholangiocarcinoma in Thai population.
References
1. Vatanasapt V, Tangvoraphonkchai V, Titapant V, Pipitgool V, Viriyapap D, Sriamporn S. A high incidence of liver cancer in Khon Kaen Province, Thailand. Southeast Asian J Trop Med Public Health 1990;21: 489-94.
2. Thamavit W, Bhamarapravati N, Sahaphong S, Vajrasthira S, Angsubhakorn S. Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. Cancer Res 1978; 38: 4634-9.
3. Parkin DM, Srivatanakul P, Khlat M, et al. Liver cancer in Thailand. A case-control study of cholangiocarcinoma. Int J Cancer 1991;48: 323-8.
4. Srivatanakul P, Ohshima H, Khlat M, et al. Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand. Int J Cancer 1991:48:821-5.
5. Satarug S, Haswell Elkins MR, Tsuda M, et al. Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection. Carcinogenesis 1996; 17:1075-81.
6. Thamavit W, Pairojkul C, Tiwawech D, Shirai T, Ito N. Strong promoting effect of Opisthorchis viverrini infection on dimethylnitrosamine-initiated hamster liver. Cancer Lett 1994;78:121-5.
7. Kirby GM, Pelkonen P, Vatanasapt V, Camus AM, Wild CP, Lang MA. Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver. Mol Carcinog 1994; 11: 81-9.
8. Puangpornpitag D. Activities and expression of CYP2E1, CYP2A6 and glutathione-S-transferase in cholangiocarcinoma liver tissue. Master thesis of Science in Medical Biochemistry, Graduate School, Khon Kaen University, 2000.
9. Vatsis KP, Weber WW, Bell DA, et al. Nomenclature for N-acetyltransferases. Pharmacogenetics 1995; 5: 1-17.
10. Hein DW, Doll MA, Rustan TD, et al. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 1993; 14: 1633-8.
11. Grant DM, Josephy PD, Lord HL, Morison LD, Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: metabolism and mutagenic activation of aromatic amines. Cancer Res 1992; 52: 3961-4.
12. Hein DW. Acetylator genotype and arylamine-induced carcinogenesis. Biochim Biophys Acta 1988; 948: 37-66.
13. Wild D, Feser W, Michel S, Lord HL, Josephy PD, Metabolic activation of heterocyclic aromatic amines catalyzed by human arylamine N-acetyltransferase isozymes (NAT1 and NAT2) expressed in Salmonella typhimurium. Carcinogenesis 1995; 16:643-8.
14. Sinha R, Caporaso N. Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved in incorporating putative genetic susceptibility markers into epidemiological studies. Ann Epidemiol 1997; 7: 350-6.
15. Badawi AF, Stern SJ, Lang NP, Kadlubar FF. Cytochrome P. 450 and acetyltransferase expression as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility. Prog Clin Biol Res 1996; 395: 109-40.
16. Badawi AF, Hirvonen A, Bell DA, Lang NP, Kadlubar FF. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer Res 1995; 55:5230-7.
17. Bell DA, Badawi AF, Lang NP, llett KF, Kadlubar FF, Hirvonen A. Polymorphism in the N-acetyltransferase 1 (NATI) polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue, Cancer Res 1995;55: 5226-9.
18. Katoh T, Kaneko S, Boissy R, Watson M, Ikemura K, Bell DA. A pilot study testing the association between N-acetyl-transferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people. Carcinogenesis 1998; 19: 1803-7.
19. Katoh T, Inatomi H, Yang M, Kawamoto T, Matsumoto T, Bell DA. Arylamine N-acetyltransferase 1 (NATI) and 2 (NAT2) genes and risk of urothelial transitional cell carcinoma among Japanese. Pharmacogenetics 1999; 9: 401-4.
20. Millikan RC, Pittman GS, Newman B, et al. Cigarette smoking. N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1998; 7: 371-8.
21. Rao KVN, Mitchison DA, Nair NGK, Prema K, Tripathy SP, Sulphadimidine acetylation test for classification of patients as slow or rapid inactivation of isoniazid, Br Med J 1970; 3:495-7.
22. McQuilkin SH, Nierenberg DW, Bresnick E., Analysis of within-subject variation of caffeine metabolism when used to determine cytochrome P450 1 A2 and N-acetyltransferase-2 activities. Cancer Epidemiol Biomarkers Prev 1995; 4: 139-46.
23. FuhrU, Rost KL. Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics 1994; 4: 109-16.
24. Miners JO, Birkett DJ. The use of caffeine as a metabolic probe for human drug metabolizing enzymes. Gen Pharmacol 1996; 27: 245-9.
25. Gu L, Gonzalez FJ, Kalow W, Tang BK, Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 1992; 2: 73-7,
26. Kukongviriyapan V, Lulitanond V, Areejitranusorn C, Kongyingyose B, Laupattarakasem P. N-acetyltransferase polymorphism in Thailand. Hum Hered 1984; 34:246-9.
27. Evans DAP. An improve and simplified method of detecting the acetylalor phenotype. J Med Genet 1969; 6: 405-7.
28. Hosmer DW, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons; 1989.
29. Mazumdar M, Glassman JR. Tutorial in biostatistics - categorizing a prognostic variable: review of methods, code for easy implementation and applications to decision making about cancer treatments. Statistics Med 1999; 19:113-32.
30. Kleinbaum DG, Logistic regression: a self-Iearning text. New York: Springer-Verlag; 1994.
31. Cartwright RA, Glashan RW, Rogers HJ, et al. Role of N-acetyltransferase phenotypes in bladder carcinogenesis: a pharmacogenetic epidemiological approach to bladder cancer. Lancet 1982; 2:842-5.
32. Risch A, Smelt V, Lane D, et al. Arylamine N-acetyltransferase in erythrocytes of cystic fibrosis patients. Pharmacol Toxicol 1996; 78: 235-40.
33. Wohlleb JC, Hunter CF, Blass B, Kadlubar FF, Chu DZ, Lang NP. Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations. Int J Cancer 1990; 46: 22-30.
34. Lang NP, Butler MA, Massengill J, et al. Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501 A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiol Biomarkers Prev 1994; 3: 675-82.
35. Hein DW, Doll MA, Fretland AJ, et al. Molecular genetics and epidemiology of the NATI and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9:29-42.
36. Landi MT, Sinha R, Lang NP, Kadlubar FF. Chapter 16. Human cytochrome P4501A2, IARC Sci Publ 1999: 173-95.
37. Nakajima M, Yokoi T, Mizutani M, Shin S, Kadlubar FF, Kamataki T, Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 1994; 3: 413-21.
38. Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T. Genetic polymorphism in the 5’-flanking region of human CYP1A2 gene; effect on the CYP1A2 inducibility in humans. J Biochem Tokyo 1999; 125: 803-8.
39. Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999; 47: 445-9.
40. FuhrU, Rost KL, Engelhardt R, et al. Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations. Pharmacogenetics 1996;6:159-76.
41. Sinha R, Rothman N, Brown ED, et al. Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501 A2 activity in humans. Cancer Res 1994;54:6154-9.
42. Landi MT, Zocchetti C, Bernuccil, et al. Cytochrome P4501A2: enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels. Cancer Epidemiol Biomarkers Prev 1996; 5: 693-8.
43. Butler MA, Lang NP, Young JF, et al. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 1992;2:116-27.
44. Catteau A, Bechtel YC, Poisson N, Bechtel PR, Bonaiti Pellie C. A population and family study of CYP1A2 using caffeine urinary metabolites. Eur J Clin Pharmacol 1995; 47:423-30
45. George J, Byth K, Farrell GC, Influence of clinicopathological variables on CYP protein expression in human liver. Gastroenterol Hepatol 1996; 11: 33-9.
46. Barker CW, Fagan JB, Pasco DS. Down-regulation of P4501 A1 and P4501A2 mRNA expression in isolated hepatocytes by oxidative stress. J Biol Chem 1994;269: 3985-90.
47. Uttaravichien T, Buddhisawasdi V. Experience of non. jaundiced cholangiocarcinoma. Hepatogastroenterology 1990;37:608-11.
48. Uttaravichien T, Bhudhisawasdi V, Pairojkul C, Pugkhem A Intrahepatic cholangiocarcinoma in Thailand. A Hepatobiliary Pancreat Surg 1999; 6: 128-35.
2. Thamavit W, Bhamarapravati N, Sahaphong S, Vajrasthira S, Angsubhakorn S. Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. Cancer Res 1978; 38: 4634-9.
3. Parkin DM, Srivatanakul P, Khlat M, et al. Liver cancer in Thailand. A case-control study of cholangiocarcinoma. Int J Cancer 1991;48: 323-8.
4. Srivatanakul P, Ohshima H, Khlat M, et al. Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand. Int J Cancer 1991:48:821-5.
5. Satarug S, Haswell Elkins MR, Tsuda M, et al. Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection. Carcinogenesis 1996; 17:1075-81.
6. Thamavit W, Pairojkul C, Tiwawech D, Shirai T, Ito N. Strong promoting effect of Opisthorchis viverrini infection on dimethylnitrosamine-initiated hamster liver. Cancer Lett 1994;78:121-5.
7. Kirby GM, Pelkonen P, Vatanasapt V, Camus AM, Wild CP, Lang MA. Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver. Mol Carcinog 1994; 11: 81-9.
8. Puangpornpitag D. Activities and expression of CYP2E1, CYP2A6 and glutathione-S-transferase in cholangiocarcinoma liver tissue. Master thesis of Science in Medical Biochemistry, Graduate School, Khon Kaen University, 2000.
9. Vatsis KP, Weber WW, Bell DA, et al. Nomenclature for N-acetyltransferases. Pharmacogenetics 1995; 5: 1-17.
10. Hein DW, Doll MA, Rustan TD, et al. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 1993; 14: 1633-8.
11. Grant DM, Josephy PD, Lord HL, Morison LD, Salmonella typhimurium strains expressing human arylamine N-acetyltransferases: metabolism and mutagenic activation of aromatic amines. Cancer Res 1992; 52: 3961-4.
12. Hein DW. Acetylator genotype and arylamine-induced carcinogenesis. Biochim Biophys Acta 1988; 948: 37-66.
13. Wild D, Feser W, Michel S, Lord HL, Josephy PD, Metabolic activation of heterocyclic aromatic amines catalyzed by human arylamine N-acetyltransferase isozymes (NAT1 and NAT2) expressed in Salmonella typhimurium. Carcinogenesis 1995; 16:643-8.
14. Sinha R, Caporaso N. Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved in incorporating putative genetic susceptibility markers into epidemiological studies. Ann Epidemiol 1997; 7: 350-6.
15. Badawi AF, Stern SJ, Lang NP, Kadlubar FF. Cytochrome P. 450 and acetyltransferase expression as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility. Prog Clin Biol Res 1996; 395: 109-40.
16. Badawi AF, Hirvonen A, Bell DA, Lang NP, Kadlubar FF. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer Res 1995; 55:5230-7.
17. Bell DA, Badawi AF, Lang NP, llett KF, Kadlubar FF, Hirvonen A. Polymorphism in the N-acetyltransferase 1 (NATI) polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue, Cancer Res 1995;55: 5226-9.
18. Katoh T, Kaneko S, Boissy R, Watson M, Ikemura K, Bell DA. A pilot study testing the association between N-acetyl-transferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people. Carcinogenesis 1998; 19: 1803-7.
19. Katoh T, Inatomi H, Yang M, Kawamoto T, Matsumoto T, Bell DA. Arylamine N-acetyltransferase 1 (NATI) and 2 (NAT2) genes and risk of urothelial transitional cell carcinoma among Japanese. Pharmacogenetics 1999; 9: 401-4.
20. Millikan RC, Pittman GS, Newman B, et al. Cigarette smoking. N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1998; 7: 371-8.
21. Rao KVN, Mitchison DA, Nair NGK, Prema K, Tripathy SP, Sulphadimidine acetylation test for classification of patients as slow or rapid inactivation of isoniazid, Br Med J 1970; 3:495-7.
22. McQuilkin SH, Nierenberg DW, Bresnick E., Analysis of within-subject variation of caffeine metabolism when used to determine cytochrome P450 1 A2 and N-acetyltransferase-2 activities. Cancer Epidemiol Biomarkers Prev 1995; 4: 139-46.
23. FuhrU, Rost KL. Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics 1994; 4: 109-16.
24. Miners JO, Birkett DJ. The use of caffeine as a metabolic probe for human drug metabolizing enzymes. Gen Pharmacol 1996; 27: 245-9.
25. Gu L, Gonzalez FJ, Kalow W, Tang BK, Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 1992; 2: 73-7,
26. Kukongviriyapan V, Lulitanond V, Areejitranusorn C, Kongyingyose B, Laupattarakasem P. N-acetyltransferase polymorphism in Thailand. Hum Hered 1984; 34:246-9.
27. Evans DAP. An improve and simplified method of detecting the acetylalor phenotype. J Med Genet 1969; 6: 405-7.
28. Hosmer DW, Lemeshow S. Applied logistic regression. New York: John Wiley & Sons; 1989.
29. Mazumdar M, Glassman JR. Tutorial in biostatistics - categorizing a prognostic variable: review of methods, code for easy implementation and applications to decision making about cancer treatments. Statistics Med 1999; 19:113-32.
30. Kleinbaum DG, Logistic regression: a self-Iearning text. New York: Springer-Verlag; 1994.
31. Cartwright RA, Glashan RW, Rogers HJ, et al. Role of N-acetyltransferase phenotypes in bladder carcinogenesis: a pharmacogenetic epidemiological approach to bladder cancer. Lancet 1982; 2:842-5.
32. Risch A, Smelt V, Lane D, et al. Arylamine N-acetyltransferase in erythrocytes of cystic fibrosis patients. Pharmacol Toxicol 1996; 78: 235-40.
33. Wohlleb JC, Hunter CF, Blass B, Kadlubar FF, Chu DZ, Lang NP. Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations. Int J Cancer 1990; 46: 22-30.
34. Lang NP, Butler MA, Massengill J, et al. Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501 A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiol Biomarkers Prev 1994; 3: 675-82.
35. Hein DW, Doll MA, Fretland AJ, et al. Molecular genetics and epidemiology of the NATI and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9:29-42.
36. Landi MT, Sinha R, Lang NP, Kadlubar FF. Chapter 16. Human cytochrome P4501A2, IARC Sci Publ 1999: 173-95.
37. Nakajima M, Yokoi T, Mizutani M, Shin S, Kadlubar FF, Kamataki T, Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 1994; 3: 413-21.
38. Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T. Genetic polymorphism in the 5’-flanking region of human CYP1A2 gene; effect on the CYP1A2 inducibility in humans. J Biochem Tokyo 1999; 125: 803-8.
39. Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999; 47: 445-9.
40. FuhrU, Rost KL, Engelhardt R, et al. Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations. Pharmacogenetics 1996;6:159-76.
41. Sinha R, Rothman N, Brown ED, et al. Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501 A2 activity in humans. Cancer Res 1994;54:6154-9.
42. Landi MT, Zocchetti C, Bernuccil, et al. Cytochrome P4501A2: enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels. Cancer Epidemiol Biomarkers Prev 1996; 5: 693-8.
43. Butler MA, Lang NP, Young JF, et al. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 1992;2:116-27.
44. Catteau A, Bechtel YC, Poisson N, Bechtel PR, Bonaiti Pellie C. A population and family study of CYP1A2 using caffeine urinary metabolites. Eur J Clin Pharmacol 1995; 47:423-30
45. George J, Byth K, Farrell GC, Influence of clinicopathological variables on CYP protein expression in human liver. Gastroenterol Hepatol 1996; 11: 33-9.
46. Barker CW, Fagan JB, Pasco DS. Down-regulation of P4501 A1 and P4501A2 mRNA expression in isolated hepatocytes by oxidative stress. J Biol Chem 1994;269: 3985-90.
47. Uttaravichien T, Buddhisawasdi V. Experience of non. jaundiced cholangiocarcinoma. Hepatogastroenterology 1990;37:608-11.
48. Uttaravichien T, Bhudhisawasdi V, Pairojkul C, Pugkhem A Intrahepatic cholangiocarcinoma in Thailand. A Hepatobiliary Pancreat Surg 1999; 6: 128-35.
Downloads
Published
2004-06-30
How to Cite
1.
Kukongviriyapan V, Aiemsa-ard J, Warasiha B, Tassaneyakul W, Bhudhisawasdi V, Saeseow O-T, Thinkhamrop B. Association of N-acelyltransferase-2 Phenotype and CYP1A2 Activity with Cholangiocarcinoma in Thailand. Thai J Surg [Internet]. 2004 Jun. 30 [cited 2024 May 7];25(2):39-46. Available from: https://he02.tci-thaijo.org/index.php/ThaiJSurg/article/view/242415
Issue
Section
Original Articles
License
Articles must be contributed solely to The Thai Journal of Surgery and when published become the property of the Royal College of Surgeons of Thailand. The Royal College of Surgeons of Thailand reserves copyright on all published materials and such materials may not be reproduced in any form without the written permission.
