Advertisement

Environmental Science and Pollution Research

, Volume 25, Issue 31, pp 31691–31704 | Cite as

Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk

  • Ravi Prakash Yadav
  • Souvik Ghatak
  • Payel Chakraborty
  • Freda Lalrohlui
  • Ravi Kannan
  • Rajeev Kumar
  • Jeremy L. Pautu
  • John Zomingthanga
  • Saia Chenkual
  • Rajendra Muthukumaran
  • Nachimuthu Senthil Kumar
Research Article
  • 41 Downloads

Abstract

In the present study, we correlated the various lifestyle habits and their associated mutations in cell cycle (P21 and MDM2) and DNA damage repair (MLH1) genes to investigate their role in gastric cancer (GC). Multifactor dimensionality reduction (MDR) analysis revealed the two-factor model of oral snuff and smoked meat as the significant model for GC risk. The interaction analysis between identified mutations and the significant demographic factors predicted that oral snuff is significantly associated with P21 3′UTR mutations. A total of five mutations in P21 gene, including three novel mutations in intron 2 (36651738G > A, 36651804A > T, 36651825G > T), were identified. In MLH1 gene, two variants were identified viz. one in exon 8 (37053568A > G; 219I > V) and a novel 37088831C > G in intron 16. Flow cytometric analysis predicted DNA aneuploidy in 07 (17.5%) and diploidy in 33 (82.5%) tumor samples. The G2/M phase was significantly arrested in aneuploid gastric tumor samples whereas high S-phase fraction was observed in all the gastric tumor samples. This study demonstrated that environmental chemical carcinogens along with alteration in cell cycle regulatory (P21) and mismatch repair (MLH1) genes may be stimulating the susceptibility of GC by altering the DNA content level abnormally in tumors in the Mizo ethic population.

Keywords

Chemical carcinogens Gastric cancer Flow cytometer Cell cycle Mutation Mizo population 

Notes

Funding

This work was supported by DBT—Advanced Level State Biotech Hub (BT/04/NE/2009 dt. 29.08.2014), Bioinformatics Infrastructure Facility (No. BT/BI/12/060/2012 (BTISNeT), and DBT eLibrary Consortium (DeLCON) sponsored by the Department of Biotechnology (DBT), New Delhi, Govt. of India, Mizoram University which provided all the essential facilities to carry out the work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest to report.

Ethics, consent, and permissions

All participants gave written informed consent to the study protocol which was approved by the Ethical Committee of the Civil Hospital, Mizoram and Mizoram University, India (B.12018/1/13-CH(A)/IEC), to conduct and publish the research work. The study protocol was also approved by the Institutional Review Board of all institutes involved in the study.

Supplementary material

11356_2018_3080_MOESM1_ESM.docx (17 kb)
Supplementary Table 1 Primers used for amplification of the p21, mdm2 and mlh1 genes. (DOCX 16 kb)

References

  1. An J-H, ASM J, Kim JW, Kim CH, Choi KH (2014) The expression of P21 is upregulated by forkhead box A1/2 in p53-null H1299 cells. FEBS Lett 588:4065–4070CrossRefGoogle Scholar
  2. Appelman HD, Mclaughlin JK, Blot WJ, Fraumeni JF (1992) A cohort study of stomach cancer in a high-risk American population. Cancer 69:2867–2868CrossRefGoogle Scholar
  3. Baba H, Korenaga D, Kakeji Y, Haraguchi M, Okamura T, Maehara Y (2002) DNA ploidy and its clinical implications in GC. Surgery 131(1 Suppl):S63–S70CrossRefGoogle Scholar
  4. Bahl R, Arora S, Nath N, Mathur M, Shukla NK, Ralhan R (2000) Novel polymorphism in P21(waf1/cip1) cyclin dependent kinase inhibitor gene: association with human esophageal cancer. Oncogene 19:323–328CrossRefGoogle Scholar
  5. Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138(6):2073–2087CrossRefGoogle Scholar
  6. Bouska A, Lushnikova T, Plaza S, Eischen CM (2008) MDM2 promotes genetic instability and transformation independent of p53. Mol Cell Biol 28:4862–4874CrossRefGoogle Scholar
  7. Brito MJ, Filipe MI, Williams GT, Thompson H, Ormerod MG, Titley J (1993) DNA ploidy in early gastric carcinoma (T1): a flow cytometric study of 100 European cases. Gut 34:230–234CrossRefGoogle Scholar
  8. Campbell PT, Curtin K, Ulrich CM, Samowitz WS, Bigler J, Velicer CM, Caan B, Potter JD, Slattery ML (2009) Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors. Gut 58:661–667CrossRefGoogle Scholar
  9. Campos F, Carrasquilla G, Koriyama C, Serra M, Carrascal E, Itoh T, Nomoto M, Akiba S (2006) Risk factors of GC specific for tumor location and histology in Cali, Colombia. World J Gastroenterol 12:5772–5779CrossRefGoogle Scholar
  10. Cattaert T, Calle ML, Dudek SM, Mahachie JJM, Van-Lishout F et al (2011) Model-based multifactor dimensionality reduction for detecting epistasis in case–control data in the presence of noise. Ann Hum Genet 75(1):78–89CrossRefGoogle Scholar
  11. Chao A, Thun MJ, Henley SJ, Jacobs EJ, Mccullough ML, Calle EE (2002) Cigarette smoking, use of other tobacco products and stomach cancer mortality in us adults: the cancer prevention study II. Int J Cancer 101:380–389CrossRefGoogle Scholar
  12. Chen C, Pearson AM, Gray JI (1990) Meat mutagens. Adv Food Nutr Res 34:387–449CrossRefGoogle Scholar
  13. Cho YG, Choi BJ, Song JH, Kim CJ, Cao Z, Nam SW, Lee JY, Park WS (2008) No association of MDM2 T309G polymorphism with susceptibility to Korean GC patients. Neoplasma 55:256–260Google Scholar
  14. Choudhury JH, Singh SA, Kundu S, Choudhury B, Talukdar FR, Srivasta S et al (2015) Tobacco carcinogen-metabolizing genes CYP1A1, GSTM1, and GSTT1 polymorphisms and their interaction with tobacco exposure influence the risk of head and neck cancer in northeast Indian population. TumorBiol 36(8):5773–5783Google Scholar
  15. Christensen LL, Madsen BE, Wikman FP, Wiuf C, Koed K, Tjonneland A (2008) The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population. BMC Med Genet 9:52–63CrossRefGoogle Scholar
  16. Ciccarelli C, Marampon F, Scoglio A, Mauro A, Giacinti C, Cesaris PD (2005) P21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation and onco-phenotype reversal in rhabdomyosarcoma cells. Mol Cancer 13(4):14Google Scholar
  17. Correa P, Fontham E, Pickle LW, Chen V, Lin YP, Haenszel W (1985) Dietary determinants of GC in south Louisiana inhabitants. J Natl Cancer Inst 75:645–654Google Scholar
  18. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, et al. (eds) (2007) Cancer incidence in five continents, vol. IX, IARC Scientific Publications No. 160. IARC, LyonGoogle Scholar
  19. Decesse JT, Medjkane S, Datto MB, Crémisi CE (2001) RB regulates transcription of the P21/WAF1/CIP1 gene. Oncogene 20(8):962–971CrossRefGoogle Scholar
  20. Dikshit R, Gupta PC, Ramasundarahettige C, Gajalakshmi V, Aleksandrowicz L, Badwe R (2012) Million death study collaborators. Cancer mortality in India: a nationally representative survey. Lancet 379:1807–1816CrossRefGoogle Scholar
  21. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M (2015) Cancer incidence and mortality worldwide, sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:359–386CrossRefGoogle Scholar
  22. Flejou JF, Potet F, Muzeau F, Le-Pelletier F, Fekete F, Henin D (1993) Overexpression of p53 protein in Barrett’s syndrome with malignant transformation. J Clin Pathol 46:330–333CrossRefGoogle Scholar
  23. Furberg H, Lichtenstein P, Pedersen NL, Bulik C, Sullivan PF (2006) Cigarettes and oral snuff use in Sweden: prevalence and transitions. Addiction 101(10):1509–1515CrossRefGoogle Scholar
  24. Gartel AL (2005) The conflicting roles of the CDK inhibitor P21(CIP1/WAF1) in apoptosis. Leuk Res 29:1237–1238CrossRefGoogle Scholar
  25. Gartel AL, Tyner AL (1999) Transcriptional regulation of the P21 (WAF/CIP1) gene. Exp Cell Res 246:280–289CrossRefGoogle Scholar
  26. Ghatak S, Muthukumaran RB, Nachimuthu SK (2013) A simple method of genomic DNA extraction from human samples for PCR-RFLP analysis. J Biomol Tech 24:224–231Google Scholar
  27. Ghatak S, Yadav RP, Lalrohlui F, Chakraborty P, Ghosh S, Ghosh S (2016) Xenobiotic pathway gene polymorphisms associated with GC in high risk Mizo-mongoloid population, northeast India. Helicobacter 21:523–535CrossRefGoogle Scholar
  28. Ghatak S, Zothansanga PJL, Nachimuthu SK (2014) Co-extraction and PCR based analysis of nucleic acids from formalin-fixed paraffin-embedded specimens. J Clin Lab Anal 29(6):485–492CrossRefGoogle Scholar
  29. Giam M, Rancati G (2015) Aneuploidy and chromosomal instability in cancer: a jackpot to chaos. Cell Div 10:3CrossRefGoogle Scholar
  30. Gleeson CM, Sloan JM, McManus DT, Maxwell P, Arthur K, McGuigan JA (1998) Comparison of p53 and DNA content abnormalities in adenocarcinoma of the oesophagus and gastric cardia. Br J Cancer 77(2):277–286CrossRefGoogle Scholar
  31. Gooding C, Clark F, Wollerton MC, Grellscheid SN, Groom H, Smith CW (2006) A class of human exons with predicted distant branch points revealed by analysis of AG dinucleotide exclusion zones. Genome Biol 7:23–31CrossRefGoogle Scholar
  32. Gravina S, Lescai F, Hurteau G, Brock GJ, Saramaki A, Salvioli S (2009) Identification of single nucleotide polymorphisms in the P21 (CDKN1A) gene and correlations with longevity in the Italian population. Aging (Albany NY) 1:470–480CrossRefGoogle Scholar
  33. Guerrette S, Acharya S, Fishel R (1999) The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer. J Biol Chem 274:6336–6341CrossRefGoogle Scholar
  34. Hahn LW, Ritchie MD, Moore JH (2003) Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics 19(3):376–382CrossRefGoogle Scholar
  35. Hecht SS (2003) Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 3:733–744CrossRefGoogle Scholar
  36. Hedley DW (1994) DNA analysis from paraffin-embedded blocks. Flow cytometry Second Edition, Part A PP: 231–240Google Scholar
  37. Igaki H, Sasaki H, Kishi T, Sakamoto H, Tachimori Y, Kato H (1994) Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines. Biochem Biophys Res Commun 203:1090–1095CrossRefGoogle Scholar
  38. Ihsan R, Devi TR, Yadav DS, Mishra AK, Sharma J, Zomawia E (2011) Investigation on the role of p53 codon 72 polymorphism and interactions with tobacco, betel quid, and alcohol in susceptibility to cancers in a high-risk population from north east India. DNA Cell Biol 30:163–171CrossRefGoogle Scholar
  39. Jung YS, Qian Y, Chen X (2010) Examination of the expanding pathways for the regulation of P21 expression and activity. Cell Signal 22(7):1003–1012CrossRefGoogle Scholar
  40. Keshava C, Frye BL, Wolff MS, McCanlies EC, Weston A (2002) Waf-1 (P21) and p53 polymorphisms in breast cancer. Cancer Epidemiol Biomark Prev 11:127–130Google Scholar
  41. Kim JC, Roh SA, Koo KH, Ka IH, Kim HC, Yu CS (2004) Genotyping possible polymorphic variants of human mismatch repair genes in healthy Korean individuals and sporadic colorectal cancer patients. Fam Cancer 3:129–137CrossRefGoogle Scholar
  42. Kneller RW, Guo WD, Hsing AW, Chen JS, Blot WJ, Li JY et al (1992) Risk factors for stomach cancer in sixty-five Chinese counties. Cancer Epidemiol Biomark Prev 1:113–118Google Scholar
  43. Kondo E, Horii A, Fukushige S (2001) The interaction domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2. Nucleic Acid Res 29:1695–1708CrossRefGoogle Scholar
  44. Kondo E, Suzuki H, Horii A, Fukushige S (2003) A yeast two-hybrid assay provides a simple way to evaluate the vast majority of hMLH1 germ-line mutations. Cancer Res 63:3302–3308Google Scholar
  45. Lin G, Fang F, Yu XJ, Yu L (2011) Meta-analysis of the relationship between P21 Ser31Arg polymorphism and lung cancer susceptibility. Genet Mol Res 10:2449–2456CrossRefGoogle Scholar
  46. Lipkin SM, Wang V, Jacoby R, Banerjee-Basu S, Baxevanis AD, Lynch HT (2000) MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet 24:27–35CrossRefGoogle Scholar
  47. Listgarten J, Damaraju S, Poulin B, Cook L, Dufour J, Driga A (2004) Predictive models for breast cancer susceptibility from multiple single nucleotide polymorphisms. Clin Cancer Res 10:2725–2737CrossRefGoogle Scholar
  48. Ma H, Zhou Z, Wei S, Wei Q (2011) Association between P21 Ser31Arg polymorphism and cancer risk: a meta-analysis. Chin J Cancer 30:254–263CrossRefGoogle Scholar
  49. Madathil S, Senthil Kumar N, Zodinpuii D, Muthukumaran RB, Lalmuanpuii R, Nicolau B (2018) TUIBUR: tobacco in a bottle—commercial production of tobacco smoke-saturated aqueous concentrate. Addiction 113:577–580.  https://doi.org/10.1111/add.14117 CrossRefGoogle Scholar
  50. Malakar M, Devi KR, Phukan RK, Kaur T, Deka M, Lalhriat-Puia L (2012) Genetic polymorphism of glutathione S-transferases M1 and T1, tobacco habits and risk of stomach cancer in Mizoram, India. Asian Pac J Cancer Prev 13(9):4725–4732CrossRefGoogle Scholar
  51. Malumbres M, Carnero A (2003) Cell cycle deregulation: a common motif in cancer. Prog Cell Cycle Res 5:5–18Google Scholar
  52. Mann A, Hogdall E, Ramus SJ, DiCioccio RA, Hogdall C, Quaye L (2008) Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients. Eur J Cancer 44:2259–2265CrossRefGoogle Scholar
  53. Manuguerra M, Matullo G, Veglia F, Autrup H, Dunning AM, Garte S (2007) Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions. Carcinogenesis 28(2):414–422CrossRefGoogle Scholar
  54. Marchetti A, Buttitta F, Pellegrini S, Merlo G, Chella A, Angeletti C (1995) MDM2 gene amplification and overexpression in non-small cell lung carcinomas with accumulation of the p53 protein in the absence of p53 gene mutations. Diagn Mol Pathol 4:93–97CrossRefGoogle Scholar
  55. Mathonnet G, Krajinovic M, Labuda D, Sinnett D (2003) Role of DNA mismatch repair genetic polymorphisms in the risk of childhood acute lymphoblastic leukaemia. Br J Haematol 123:45–48CrossRefGoogle Scholar
  56. Merkel DE, Mcguire WL (1990) Ploidy, proliferative activity and prognosis. Cancer 65:1194–1205CrossRefGoogle Scholar
  57. Mousses S, Ozcelik H, Lee PD, Malkin D, Bull SB, Andrulis IL (1995) Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer. Hum Mol Genet 4:1089–1092CrossRefGoogle Scholar
  58. Nanus DM, Kelsen DP, Niedzwiecki D, Chapman D, Brennan M, Cheng E (1989) Flow cytometry as a predictive indicator in patients with operable GC. J Clin Oncol 7(8):1105–1112CrossRefGoogle Scholar
  59. National Cancer Registry Programme (2013) Three-year report of the population based cancer registries 2011–2013. National cancer registry programme, Indian Council of Medical Research (ICMR), Bangalore, India. Available from, http://www.pbcrin-dia.org. Accessed 16 Oct 2014
  60. Nomura A, Grove JS, Stemmermann GN, Severson RK et al (1990) A prospective study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption. Cancer Res 50:627–631Google Scholar
  61. Oren M, Damalas A, Gottlieb T, Michael D, Taplick J, Leal JF (2002) Regulation of p53: intricate loops and delicate balances. Biochem Pharmacol 64:865–871CrossRefGoogle Scholar
  62. Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A (1995) p53-independent expression of P21Cip1 in muscle and other terminally differentiating cells. Science 267(5200):1024–1027CrossRefGoogle Scholar
  63. Petersen SM, Dandanell M, Rasmussen LJ, Gerdes AM, Krogh LN, Bernstein I (2013) Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients. BMC Med Genet 14:103–114CrossRefGoogle Scholar
  64. Phillips DH (1999) Polycyclic aromatic hydrocarbons in the diet. Mutat Res 443:139–147CrossRefGoogle Scholar
  65. Phukan RK, Hazarika NC, Baruah D, Mahanta J (2004) High prevalence of stomach cancer among the people of Mizoram, India. Curr Sci 87:285–286Google Scholar
  66. Phukan RK, Narain K, Zomawia E, Hazarika NC, Mahanta J (2006) Dietary habits and stomach cancer in Mizoram, India. J Gastroenterol 41:418–424CrossRefGoogle Scholar
  67. Phukan RK, Zomawia E, Narain K, Hazarika NC, Mahanta J (2005) Tobacco use and stomach cancer in Mizoram, India. Cancer Epidemiol Biomark Prev 14:1892–1896CrossRefGoogle Scholar
  68. Piazuelo MB, Correa P (2013) Gastric cáncer: overview. Colomb Med (Cali) 44(3):192–201Google Scholar
  69. Quirke DP, Dixon MF, Clayden AD, Durdey P, Dyson JED, Williams NS (2005) Prognostic significance of DNA aneuploidy and cell proliferation in rectal adenocarcinomas. J Pathol 151(4):285–291CrossRefGoogle Scholar
  70. Raevaara TE, Korhonen MK, Lohi H, Hampel H, Lynch E, Lönnqvist KE (2005) Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1. Gastroenterology 129:537–549Google Scholar
  71. Raptis S, Mrkonjic M, Green RC, Pethe VV, Monga N, Chan YM (2007) MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer. J Natl Cancer Inst 99:463–474CrossRefGoogle Scholar
  72. Ritchie MD, Hahn LW, Moore JH (2003) Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genet Epidemiol 24(2):150–157CrossRefGoogle Scholar
  73. Santarelli RL, Pierre F, Corpet DE (2008) Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence. Nutr Cancer 60(2):131–144CrossRefGoogle Scholar
  74. Sauli E, Hongna L, Vedastus AK, Weiyue H, Song L, Nongyue H (2015) Polymorphisms in NEIL-2, APE-1, CYP2E1 and MDM2 genes are independent predictors of GC risk in a northern Jiangsu population (China). J Nanosci Nanotechnol 15(7):4815–4828CrossRefGoogle Scholar
  75. Shiohara M, Deiry WE, Wada M, Nakamaki T, Takeuchi S, Yang R (1994) Absence of WAF1 mutations in a variety of human malignancies. Nature 84:3781–3784Google Scholar
  76. Stepanov I, Hecht SS, Ramakrishnan S, Gupta PC (2005) Tobacco-specific nitrosamines in smokeless tobacco products marketed in India. Int J Cancer 116(1):16–19CrossRefGoogle Scholar
  77. Stepanov I, Villalta PW, Knezevich A, Jensen J, Hatsukami DK, Hecht SS (2010) Analysis of 23 polycyclic aromatic hydrocarbons in smokeless tobacco by gas chromatography–mass spectrometry. Chem Res Toxicol 23(1):66–73CrossRefGoogle Scholar
  78. Sumathi B, Ramalingam S, Navaneethan U, Jayanthi V (2009) Risk factors for GC in South India. Singap Med J 50:147–151Google Scholar
  79. Torre L, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global Cancer Statistics, 2012. CA Cancer J Clin 65:87–108CrossRefGoogle Scholar
  80. Trojan J, Zeuzem S, Randolph A, Hemmerle C, Brieger A, Raedle J (2002) Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. Gastroenterology 122:211–219CrossRefGoogle Scholar
  81. Tsugane S, Sasazuki S (2007) Diet and the risk of GC: review of epidemiological evidence. Gastric Cancer 10:75–83CrossRefGoogle Scholar
  82. Tsugane S, Sasazuki S, Kobayashi M, Sasaki S (2004) Salt and salted food intake and subsequent risk of GC among middle-aged Japanese men and women. Br J Cancer 90:128–134CrossRefGoogle Scholar
  83. Wang X, Wang J, Huang V, Place RF, Li LC (2012) Induction of NANOG expression by targeting promoter sequence with small activating RNA antagonizes retinoic acid-induced differentiation. Biochem J 443:821–828CrossRefGoogle Scholar
  84. Ward MH, Lopez-Carrillo L (1999) Dietary factors and the risk of GC in Mexico City. Am J Epidemiol 149:925–392CrossRefGoogle Scholar
  85. Watanabe H, Fukuchi K, Takagi Y, Tomoyasu S, Tsuruoka N, Gomia K (1995) Molecular analysis of the Cip1/Waf1 (P21) gene in diverse types of human tumors. Biochim Biophys Acta 1263:275–280CrossRefGoogle Scholar
  86. Yaghoobi M, Bijarchi R, Narod SA (2010) Family history and the risk of GC. Br J Cancer 102(2):237–242CrossRefGoogle Scholar
  87. Yan L, Fang L, Sha Z, Suqing S, Li L, Lifeng L (2015) Genetics and GC susceptibility. Int J Clin Exp Med 8(6):8377–8383Google Scholar
  88. Yeh JM, Kuntz KM, Ezzati M, Goldie SJ (2009) Exploring the cost-effectiveness of Helicobacter pylori screening to prevent GC in China in anticipation of clinical trial results. Int J Cancer 124:157–166CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ravi Prakash Yadav
    • 1
  • Souvik Ghatak
    • 1
  • Payel Chakraborty
    • 1
  • Freda Lalrohlui
    • 1
  • Ravi Kannan
    • 2
  • Rajeev Kumar
    • 2
  • Jeremy L. Pautu
    • 3
  • John Zomingthanga
    • 4
  • Saia Chenkual
    • 5
  • Rajendra Muthukumaran
    • 6
  • Nachimuthu Senthil Kumar
    • 1
  1. 1.Department of BiotechnologyMizoram UniversityAizawlIndia
  2. 2.Cachar Cancer Hospital and Research CentreSilcharIndia
  3. 3.Mizoram State Cancer InstituteAizawlIndia
  4. 4.Department of PathologyCivil HospitalAizawlIndia
  5. 5.Department of SurgeryCivil HospitalAizawlIndia
  6. 6.Department of ChemistryMizoram UniversityAizawlIndia

Personalised recommendations