Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation

Sayan Paul; Tamojit Chaudhuri; M. C. Pant; D. Parmar; Kirti Srivastava

doi:10.4103/2278-330X.136771

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MINI SYMPOSIUM: HEAD AND NECK CANCER : Original Article

03 (

); 154-158

doi:

10.4103/2278-330X.136771

Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation

Sayan Paul¹, Tamojit Chaudhuri^2,, M. C. Pant¹, D. Parmar³, Kirti Srivastava¹

1 Departments of Radiotherapy, Chhatrapati Shahuji Maharaj Medical University, Formerly, King George’s Medical University, Lucknow

2 Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow

3 Department of Developmental Toxicology and Environmental Epidemiology, Indian Institute of Toxicology and Research, Lucknow, Uttar Pradesh, India

*Corresponding author: Dr. Tamojit Chaudhuri. tamojit.cnmc@gmail.com

Published: 2020-12-31

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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Abstract

Aims: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9) enzyme with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving cisplatin-based radical chemoradiation (CT-RT). Materials and Methods: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs) by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO) criteria. Results and Analysis: The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.8%) and CYP2C9FNx013 (25%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (n = 436) carrying variant alleles of CYP2C9FNx012 (69.6%) or CYP2C9FNx013 (65.2%) were found to respond poorly to cisplatin-based radical CT-RT. Conclusion: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol.

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References

Hunter KD, Parkinson EK, Harrison PR. Profiling early head and neck cancer. Nat Rev Cancer 2005;5:127-35.
Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev 2000;9:3-28.
Hashibe M, Brennan P, Strange RC, Bhisey R, Cascorbi I, Lazarus P, et al. Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev 2003;12:1509-17.
Van Schaik RH. Cancer treatment and pharmacogenetics of cytochrome P450 enzymes . Invest New Drugs 2005;23:513-22.
Griskevicius L, Yasar U, Sandberg M, Hidestrand M, Eliasson E, Tybring G, et al. Bioactivation of cyclophosphamide: The role of polymorphic CYP2C enzymes. Eur J Clin Pharmacol 2003;59:103-9.
Shou M, Korzekwa KR, Krausz KW, Buters JT, Grogan J, Goldfarb I, et al. Specificity of cDNA-expressed human and rodent cytochrome P450s in the oxidative metabolism of the potent carcinogen 7, 12-dimethylbenz[a] anthracene. Mol Carcinog 1996;17:241-9.
Bauer E, Guo Z, Ueng YF, Bell LC, Zeldin D, Guengerich FP. Oxidation of benzo[a] pyrene by recombinant human cytochrome P450 enzymes. Chem Res Toxicol 1995;8:136-42.
Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002;287:1690-8.
Wang SL, Huang J, Lai MD, Tsai JJ. Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 1995;5:37-42.
London SJ, Daly AK, Leathart JB, Navidi WC, Idle JR. Lung cancer risk in relation to the CYP2C9FNx011/CYP2C9FNx012 genetic polymorphism among African-Americans and Caucasians in Los Angeles County, California. Pharmacogenetics 1996;6:527-33.
Chan AT, Tranah GJ, Giovannucci EL, Hunter DJ, Fuchs CS. A prospective study of genetic polymorphisms in the cytochrome P-450 2C9 enzyme and the risk for distal colorectal adenoma. Clin Gastroenterol Hepatol 2004;2:704-12.
Sikdar N, Mahmud SA, Paul RR, Roy B. Polymorphism in CYP1A1 and CYP2E1 genes and susceptibility to leukoplakia in Indian tobacco users. Cancer Lett 2003;195:33-42.
Hung HC, Chuang J, Chien YC, Chern HD, Chiang CP, Kuo YS, et al. Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer. Cancer Epidemiol Biomarkers Prev 1997;6:901-5.
Yadav SS, Ruwali M, Shah PP, Mathur N, Singh RL, Pant MC, et al. Association of poor metabolizers of cytochrome P450 2C19 with head and neck cancer and poor treatment response. Mutat Res 2008;644:31-7.
Adithan C, Gerard N, Vasu S, Balakrishnan R, Shashindran CH, Krishnamoorthy R. Allele and genotype frequency of CYP2C9 in Tamilnadu population. Eur J Clin Pharmacol 2003;59:707-9.
Jose R, Chandrasekaran A, Sam SS, Gerard N, Chanolean S, Abraham BK, et al. CYP2C9 and CYP2C19 genetic polymorphisms: Frequencies in the south Indian population. Fundam Clin Pharmacol 2005;19:101-5.
Chang TK, Yu L, Goldstein JA, Waxman DJ. Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics 1997;7:211-21.
Hamitouche S, Poupon J, Dreano Y, Amet Y, Lucas D. Ethanol oxidation into acetaldehyde by 16 recombinant human cytochrome P450 isoforms: Role of CYP2C isoforms in human liver microsomes. Toxicol Lett 2006;167:221-30.
Ruwali M, Pant MC, Shah PP, Mishra BN, Parmar D. Polymorphism in cytochrome P450 2A6 and glutathione S-transferase P1 modifies head and neck cancer risk and treatment outcome. Mutat Res 2009;669:36-41.
Yadav SS, Ruwali M, Pant MC, Shukla P, Singh RL, Parmar D. Interaction of drug metabolizing cytochrome P450 2D6 poor metabolizers with cytochrome P450 2C9 and 2C19 genotypes modify the susceptibility to head and neck cancer and treatment response. Mutat Res 2010;684:49-55.

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[1] Hunter KD, Parkinson EK, Harrison PR. Profiling early head and neck cancer. Nat Rev Cancer 2005;5:127-35.

[2] Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev 2000;9:3-28.

[3] Hashibe M, Brennan P, Strange RC, Bhisey R, Cascorbi I, Lazarus P, et al. Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer. Cancer Epidemiol Biomarkers Prev 2003;12:1509-17.

[4] Van Schaik RH. Cancer treatment and pharmacogenetics of cytochrome P450 enzymes . Invest New Drugs 2005;23:513-22.

[5] Griskevicius L, Yasar U, Sandberg M, Hidestrand M, Eliasson E, Tybring G, et al. Bioactivation of cyclophosphamide: The role of polymorphic CYP2C enzymes. Eur J Clin Pharmacol 2003;59:103-9.

[6] Shou M, Korzekwa KR, Krausz KW, Buters JT, Grogan J, Goldfarb I, et al. Specificity of cDNA-expressed human and rodent cytochrome P450s in the oxidative metabolism of the potent carcinogen 7, 12-dimethylbenz[a] anthracene. Mol Carcinog 1996;17:241-9.

[7] Bauer E, Guo Z, Ueng YF, Bell LC, Zeldin D, Guengerich FP. Oxidation of benzo[a] pyrene by recombinant human cytochrome P450 enzymes. Chem Res Toxicol 1995;8:136-42.

[8] Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002;287:1690-8.

[9] Wang SL, Huang J, Lai MD, Tsai JJ. Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 1995;5:37-42.

[10] London SJ, Daly AK, Leathart JB, Navidi WC, Idle JR. Lung cancer risk in relation to the CYP2C9FNx011/CYP2C9FNx012 genetic polymorphism among African-Americans and Caucasians in Los Angeles County, California. Pharmacogenetics 1996;6:527-33.

[11] Chan AT, Tranah GJ, Giovannucci EL, Hunter DJ, Fuchs CS. A prospective study of genetic polymorphisms in the cytochrome P-450 2C9 enzyme and the risk for distal colorectal adenoma. Clin Gastroenterol Hepatol 2004;2:704-12.

[12] Sikdar N, Mahmud SA, Paul RR, Roy B. Polymorphism in CYP1A1 and CYP2E1 genes and susceptibility to leukoplakia in Indian tobacco users. Cancer Lett 2003;195:33-42.

[13] Hung HC, Chuang J, Chien YC, Chern HD, Chiang CP, Kuo YS, et al. Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer. Cancer Epidemiol Biomarkers Prev 1997;6:901-5.

[14] Yadav SS, Ruwali M, Shah PP, Mathur N, Singh RL, Pant MC, et al. Association of poor metabolizers of cytochrome P450 2C19 with head and neck cancer and poor treatment response. Mutat Res 2008;644:31-7.

[15] Adithan C, Gerard N, Vasu S, Balakrishnan R, Shashindran CH, Krishnamoorthy R. Allele and genotype frequency of CYP2C9 in Tamilnadu population. Eur J Clin Pharmacol 2003;59:707-9.

[16] Jose R, Chandrasekaran A, Sam SS, Gerard N, Chanolean S, Abraham BK, et al. CYP2C9 and CYP2C19 genetic polymorphisms: Frequencies in the south Indian population. Fundam Clin Pharmacol 2005;19:101-5.

[17] Chang TK, Yu L, Goldstein JA, Waxman DJ. Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics 1997;7:211-21.

[18] Hamitouche S, Poupon J, Dreano Y, Amet Y, Lucas D. Ethanol oxidation into acetaldehyde by 16 recombinant human cytochrome P450 isoforms: Role of CYP2C isoforms in human liver microsomes. Toxicol Lett 2006;167:221-30.

[19] Ruwali M, Pant MC, Shah PP, Mishra BN, Parmar D. Polymorphism in cytochrome P450 2A6 and glutathione S-transferase P1 modifies head and neck cancer risk and treatment outcome. Mutat Res 2009;669:36-41.

[20] Yadav SS, Ruwali M, Pant MC, Shukla P, Singh RL, Parmar D. Interaction of drug metabolizing cytochrome P450 2D6 poor metabolizers with cytochrome P450 2C9 and 2C19 genotypes modify the susceptibility to head and neck cancer and treatment response. Mutat Res 2010;684:49-55.

Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation

Abstract

Abstract

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