N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to bladder cancer in Bangladeshi population
Aim To investigate the association between the three most common single nucleotide polymorphisms of the N‐acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. Methods A case‐control study on 102 bladder cancer patients and 140 con...
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Published in | Asia-Pacific journal of clinical oncology Vol. 11; no. 1; pp. 78 - 84 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Australia
Blackwell Publishing Ltd
01.03.2015
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Abstract | Aim
To investigate the association between the three most common single nucleotide polymorphisms of the N‐acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness.
Methods
A case‐control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N‐acetyltransferase 2 alleles were differentiated by polymerase chain reaction‐based restriction fragment length polymorphism methods.
Results
Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N‐acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio = 4.45; 95% confidence interval = 2.26–8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio = 6.05; 95% confidence interval = 2.23–15.82). Patients with slow acetylating genotypes were more prone to develop high‐grade (odds ratio = 6.63; 95% confidence interval = 1.15–38.13; P < 0.05) and invasive (odds ratio = 10.6; 95% confidence interval = 1.00–111.5; P = 0.05) tumor.
Conclusion
N‐acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N‐acetyltransferase 2 slow genotypes were more likely to develop a high‐grade and invasive tumor. N‐acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. |
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AbstractList | To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness.AIMTo investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness.A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods.METHODSA case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods.Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor.RESULTSBladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor.N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population.CONCLUSIONN-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. Aim To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. Methods A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods. Results Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. Conclusion N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods. Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. Aim To investigate the association between the three most common single nucleotide polymorphisms of the N‐acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. Methods A case‐control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N‐acetyltransferase 2 alleles were differentiated by polymerase chain reaction‐based restriction fragment length polymorphism methods. Results Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N‐acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio = 4.45; 95% confidence interval = 2.26–8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio = 6.05; 95% confidence interval = 2.23–15.82). Patients with slow acetylating genotypes were more prone to develop high‐grade (odds ratio = 6.63; 95% confidence interval = 1.15–38.13; P < 0.05) and invasive (odds ratio = 10.6; 95% confidence interval = 1.00–111.5; P = 0.05) tumor. Conclusion N‐acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N‐acetyltransferase 2 slow genotypes were more likely to develop a high‐grade and invasive tumor. N‐acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. |
Author | Salam, Md. Abdus Kabir, Yearul Hosen, Md. Bayejid Hawlader, M Zakir Hossain Islam, Jahidul Islam, Md. Fakhrul |
Author_xml | – sequence: 1 givenname: Md. Bayejid surname: Hosen fullname: Hosen, Md. Bayejid organization: Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh – sequence: 2 givenname: Jahidul surname: Islam fullname: Islam, Jahidul organization: Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh – sequence: 3 givenname: Md. Abdus surname: Salam fullname: Salam, Md. Abdus organization: Department of Urology, National Institute of Kidney Diseases and Urology, Dhaka, Bangladesh – sequence: 4 givenname: Md. Fakhrul surname: Islam fullname: Islam, Md. Fakhrul organization: Department of Urology, Bangladesh Medical College and Hospital, Dhaka, Bangladesh – sequence: 5 givenname: M Zakir Hossain surname: Hawlader fullname: Hawlader, M Zakir Hossain organization: Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh – sequence: 6 givenname: Yearul surname: Kabir fullname: Kabir, Yearul email: ykabir@yahoo.com organization: Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh |
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References | Lucia KK, Viera H, Monika SO et al. Effect of NAT2 gene polymorphism on bladder cancer risk in Slovak population. Mol Biol Rep 2011; 38: 1287-1293. Zaid RB, Nargis M, Neelotpol S et al. Acetylation phenotype status in a Bangladeshi population and its comparison with that of other Asian population data. Biopharm Drug Dispos 2004; 25: 237-241. Hein H. N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene 2006; 25: 1649-1658. Inatomi H, Katoh K, Kawamoto T et al. NAT2 gene polymorphism as a possible biomarker for susceptibility to bladder cancer in Japanese. Int J Urol 1999; 6: 446-454. Rouissi K, Slah O, Bechr H et al. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia. Pathol Oncol Res 2011; 17: 879-886. Hung RJ, Boffetta P, Brennan P et al. GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population. Int J Cancer 2004; 110: 598-604. Mittal RD, Srivastava DSL, Anil M. NAT2 gene polymorphism in bladder cancer: a study from North India. Int Braz J Urol 2004; 30: 279-288. Tania C, Avima MR, Paul AS et al. NAT2 slow acetylation and bladder cancer in workers exposed to benzidine. Int J Cancer 2006; 118: 161-168. Garcia-Closas M, Malats N, Silverman D et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 2005; 366: 649-659. Badawi AF, Hirvonen A, Bell DA et al. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer Res 1995; 55: 5230-5237. Okkels H, Sigsgaard T, Wolf H et al. Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking. Cancer Epidemiol Biomarkers Prev 1997; 6: 225-231. Kadlubar FF, Badawi AF. Genetic susceptibility and carcinogen-DNA adduct formation in human urinary bladder carcinogenesis. Toxicol Lett 1995; 825: 627-632. Xie HG, Xu ZH, Ou-Yang DS. Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese population. Pharmacogenetics 1997; 7: 507-514. Miller MC, Mohrenweiser HW, Bell DA. Genetic variability in susceptibility and response to toxicants. Toxicol Lett 2001; 120: 269-280. Georgiadis P, Topinka1 J, Vlachodimitropoulos D et al. Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations. Carcinogenesis 2005; 26 (1): 93-101. Gu J, Liang D, Wang Y et al. Effects of N-acetyltransferase 1 and 2 polymorphisms on bladder cancer risk in Caucasians. Mutat Res 2005; 581: 97-104. Vineis P, Marinelli D, Autrup H et al. Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: a pooled analysis of genotype-based studies. Cancer Epidemiol Biomarkers Prev 2001; 10: 1249-1252. Song DK, Xing DL, Zhang LR et al. Association of NAT 2, GSTM1, GSTT1, CYP2A6 and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China. Cancer Detect Prev 2009; 32: 416-442. Marcus PM, Vineis P, Rothman N. NAT2 slow acetylation and bladder cancer risk: a meta-analysis of 22 case-control studies conducted in the general population. Pharmacogenetics 2000; 10: 115-122. Franekova M, Halasova E, Bukovska E, Luptak J, Dobrota D. Gene polymorphisms in bladder cancer. Urol Oncol 2008; 26: 1-8. Bryan RT, Hussain SA, James ND et al. Molecular pathways in bladder cancer. Part 1. BJU Int 2005; 95: 485-490. Vineis P, Pirastu R. Aromatic amines and cancer. Cancer Causes Control 1997; 8: 346-355. Anitha A, Banerjee M. Arylamine N-acetyltransferase 2 polymorphism in the ethnic population of South Indians. Int J Mol Med 2003; 11: 125-131. Dong LM, Potter JD, White E et al. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 2008; 299: 2423-2436. Longuemaux S, Delomenıe C, Gallou C et al. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. Cancer Res 1999; 59: 2903-2908. Filiadis IF, Georgiou I, Alamanos Y et al. Genotypes of N-acetyltransferase-2 and risk of bladder cancer: a case-control study. J Urol 1999; 161: 1672-1675. Bailes SM, Devers JJ, Kirby JD et al. An inexpensive, simple protocol for DNA isolation from blood for high-throughput genotyping by polymerase chain reaction or restriction endonuclease digestion. Poultry Sci 2007; 86: 102-106. Tsukino H, Nakao H, Kuroda Y et al. Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking. Eur J Cancer Prev 2004; 13: 509-514. Golka K, Prior V, Blaszkewicz M et al. The enhanced bladder cancer susceptibility of NAT2 slow acetylators towards aromatic amines: a review considering ethnic differences. Toxicol Lett 2002; 128: 229-241. 2001; 120 2004; 25 1995; 55 2003 2005; 26 2011; 17 2011; 38 1997; 6 1999; 6 2006; 118 1997; 7 2003; 11 1997; 8 2004; 110 2004; 30 2009; 32 2005; 581 2005; 366 2000; 10 1999; 161 1995; 825 1999; 59 2006; 25 2004; 13 2005; 95 2002; 128 2008; 26 2007; 86 2008; 299 2001; 10 |
References_xml | – reference: Garcia-Closas M, Malats N, Silverman D et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 2005; 366: 649-659. – reference: Xie HG, Xu ZH, Ou-Yang DS. Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese population. Pharmacogenetics 1997; 7: 507-514. – reference: Hein H. N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene 2006; 25: 1649-1658. – reference: Okkels H, Sigsgaard T, Wolf H et al. Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking. Cancer Epidemiol Biomarkers Prev 1997; 6: 225-231. – reference: Song DK, Xing DL, Zhang LR et al. Association of NAT 2, GSTM1, GSTT1, CYP2A6 and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China. Cancer Detect Prev 2009; 32: 416-442. – reference: Tsukino H, Nakao H, Kuroda Y et al. Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking. Eur J Cancer Prev 2004; 13: 509-514. – reference: Badawi AF, Hirvonen A, Bell DA et al. Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. Cancer Res 1995; 55: 5230-5237. – reference: Filiadis IF, Georgiou I, Alamanos Y et al. Genotypes of N-acetyltransferase-2 and risk of bladder cancer: a case-control study. J Urol 1999; 161: 1672-1675. – reference: Zaid RB, Nargis M, Neelotpol S et al. Acetylation phenotype status in a Bangladeshi population and its comparison with that of other Asian population data. Biopharm Drug Dispos 2004; 25: 237-241. – reference: Kadlubar FF, Badawi AF. Genetic susceptibility and carcinogen-DNA adduct formation in human urinary bladder carcinogenesis. Toxicol Lett 1995; 825: 627-632. – reference: Tania C, Avima MR, Paul AS et al. NAT2 slow acetylation and bladder cancer in workers exposed to benzidine. Int J Cancer 2006; 118: 161-168. – reference: Miller MC, Mohrenweiser HW, Bell DA. Genetic variability in susceptibility and response to toxicants. Toxicol Lett 2001; 120: 269-280. – reference: Gu J, Liang D, Wang Y et al. Effects of N-acetyltransferase 1 and 2 polymorphisms on bladder cancer risk in Caucasians. Mutat Res 2005; 581: 97-104. – reference: Georgiadis P, Topinka1 J, Vlachodimitropoulos D et al. Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations. Carcinogenesis 2005; 26 (1): 93-101. – reference: Longuemaux S, Delomenıe C, Gallou C et al. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. Cancer Res 1999; 59: 2903-2908. – reference: Marcus PM, Vineis P, Rothman N. NAT2 slow acetylation and bladder cancer risk: a meta-analysis of 22 case-control studies conducted in the general population. Pharmacogenetics 2000; 10: 115-122. – reference: Vineis P, Pirastu R. Aromatic amines and cancer. Cancer Causes Control 1997; 8: 346-355. – reference: Bailes SM, Devers JJ, Kirby JD et al. An inexpensive, simple protocol for DNA isolation from blood for high-throughput genotyping by polymerase chain reaction or restriction endonuclease digestion. Poultry Sci 2007; 86: 102-106. – reference: Vineis P, Marinelli D, Autrup H et al. Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: a pooled analysis of genotype-based studies. Cancer Epidemiol Biomarkers Prev 2001; 10: 1249-1252. – reference: Anitha A, Banerjee M. Arylamine N-acetyltransferase 2 polymorphism in the ethnic population of South Indians. Int J Mol Med 2003; 11: 125-131. – reference: Mittal RD, Srivastava DSL, Anil M. NAT2 gene polymorphism in bladder cancer: a study from North India. Int Braz J Urol 2004; 30: 279-288. – reference: Golka K, Prior V, Blaszkewicz M et al. The enhanced bladder cancer susceptibility of NAT2 slow acetylators towards aromatic amines: a review considering ethnic differences. Toxicol Lett 2002; 128: 229-241. – reference: Hung RJ, Boffetta P, Brennan P et al. GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population. Int J Cancer 2004; 110: 598-604. – reference: Bryan RT, Hussain SA, James ND et al. Molecular pathways in bladder cancer. Part 1. BJU Int 2005; 95: 485-490. – reference: Lucia KK, Viera H, Monika SO et al. Effect of NAT2 gene polymorphism on bladder cancer risk in Slovak population. Mol Biol Rep 2011; 38: 1287-1293. – reference: Rouissi K, Slah O, Bechr H et al. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia. Pathol Oncol Res 2011; 17: 879-886. – reference: Franekova M, Halasova E, Bukovska E, Luptak J, Dobrota D. Gene polymorphisms in bladder cancer. Urol Oncol 2008; 26: 1-8. – reference: Dong LM, Potter JD, White E et al. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 2008; 299: 2423-2436. – reference: Inatomi H, Katoh K, Kawamoto T et al. NAT2 gene polymorphism as a possible biomarker for susceptibility to bladder cancer in Japanese. 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To investigate the association between the three most common single nucleotide polymorphisms of the N‐acetyltransferase 2 gene together with cigarette... To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking... Aim To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette... |
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SubjectTerms | acetyltransferase Aged aromatic amine Arylamine N-Acetyltransferase - genetics Bangladesh - epidemiology Biomarkers, Tumor - genetics bladder cancer Case-Control Studies Female Follow-Up Studies Genetic Predisposition to Disease Genotype Humans Male Middle Aged Neoplasm Staging Polymerase Chain Reaction polymorphism Polymorphism, Restriction Fragment Length Polymorphism, Single Nucleotide - genetics Prognosis Risk Factors smoking Smoking - genetics Urinary Bladder Neoplasms - enzymology Urinary Bladder Neoplasms - epidemiology Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology |
Title | N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to bladder cancer in Bangladeshi population |
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