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

Springer Science and Business Media LLC - Tập 25 - Trang 31691-31704 - 2018
Ravi Prakash Yadav1, Souvik Ghatak1, Payel Chakraborty1, Freda Lalrohlui1, Ravi Kannan2, Rajeev Kumar2, Jeremy L. Pautu3, John Zomingthanga4, Saia Chenkual5, Rajendra Muthukumaran6, Nachimuthu Senthil Kumar1
1Department of Biotechnology, Mizoram University, Aizawl, India
2Cachar Cancer Hospital and Research Centre, Silchar, India
3Mizoram State Cancer Institute, Aizawl, India
4Department of Pathology, Civil Hospital, Aizawl, India
5Department of Surgery, Civil Hospital, Aizawl, India
6Department of Chemistry, Mizoram University, Aizawl, India

Tóm tắt

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.

Tài liệu tham khảo

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 588:4065–4070 Appelman HD, Mclaughlin JK, Blot WJ, Fraumeni JF (1992) A cohort study of stomach cancer in a high-risk American population. Cancer 69:2867–2868 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–S70 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 19:323–328 Boland CR, Goel A (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138(6):2073–2087 Bouska A, Lushnikova T, Plaza S, Eischen CM (2008) MDM2 promotes genetic instability and transformation independent of p53. Mol Cell Biol 28:4862–4874 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 34:230–234 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 58:661–667 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 12:5772–5779 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):78–89 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 101:380–389 Chen C, Pearson AM, Gray JI (1990) Meat mutagens. Adv Food Nutr Res 34:387–449 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 55:256–260 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):5773–5783 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 9:52–63 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):14 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 75:645–654 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, Lyon Decesse JT, Medjkane S, Datto MB, Crémisi CE (2001) RB regulates transcription of the P21/WAF1/CIP1 gene. Oncogene 20(8):962–971 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 379:1807–1816 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 136:359–386 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 46:330–333 Furberg H, Lichtenstein P, Pedersen NL, Bulik C, Sullivan PF (2006) Cigarettes and oral snuff use in Sweden: prevalence and transitions. Addiction 101(10):1509–1515 Gartel AL (2005) The conflicting roles of the CDK inhibitor P21(CIP1/WAF1) in apoptosis. Leuk Res 29:1237–1238 Gartel AL, Tyner AL (1999) Transcriptional regulation of the P21 (WAF/CIP1) gene. Exp Cell Res 246:280–289 Ghatak S, Muthukumaran RB, Nachimuthu SK (2013) A simple method of genomic DNA extraction from human samples for PCR-RFLP analysis. J Biomol Tech 24:224–231 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 21:523–535 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):485–492 Giam M, Rancati G (2015) Aneuploidy and chromosomal instability in cancer: a jackpot to chaos. Cell Div 10:3 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):277–286 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 7:23–31 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) 1:470–480 Guerrette S, Acharya S, Fishel R (1999) The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer. J Biol Chem 274:6336–6341 Hahn LW, Ritchie MD, Moore JH (2003) Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics 19(3):376–382 Hecht SS (2003) Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 3:733–744 Hedley DW (1994) DNA analysis from paraffin-embedded blocks. Flow cytometry Second Edition, Part A PP: 231–240 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 203:1090–1095 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 30:163–171 Jung YS, Qian Y, Chen X (2010) Examination of the expanding pathways for the regulation of P21 expression and activity. Cell Signal 22(7):1003–1012 Keshava C, Frye BL, Wolff MS, McCanlies EC, Weston A (2002) Waf-1 (P21) and p53 polymorphisms in breast cancer. Cancer Epidemiol Biomark Prev 11:127–130 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 3:129–137 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 1:113–118 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 29:1695–1708 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 63:3302–3308 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 10:2449–2456 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 24:27–35 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 10:2725–2737 Ma H, Zhou Z, Wei S, Wei Q (2011) Association between P21 Ser31Arg polymorphism and cancer risk: a meta-analysis. Chin J Cancer 30:254–263 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 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):4725–4732 Malumbres M, Carnero A (2003) Cell cycle deregulation: a common motif in cancer. Prog Cell Cycle Res 5:5–18 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 44:2259–2265 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):414–422 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 4:93–97 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 123:45–48 Merkel DE, Mcguire WL (1990) Ploidy, proliferative activity and prognosis. Cancer 65:1194–1205 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 4:1089–1092 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):1105–1112 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 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 50:627–631 Oren M, Damalas A, Gottlieb T, Michael D, Taplick J, Leal JF (2002) Regulation of p53: intricate loops and delicate balances. Biochem Pharmacol 64:865–871 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):1024–1027 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 14:103–114 Phillips DH (1999) Polycyclic aromatic hydrocarbons in the diet. Mutat Res 443:139–147 Phukan RK, Hazarika NC, Baruah D, Mahanta J (2004) High prevalence of stomach cancer among the people of Mizoram, India. Curr Sci 87:285–286 Phukan RK, Narain K, Zomawia E, Hazarika NC, Mahanta J (2006) Dietary habits and stomach cancer in Mizoram, India. J Gastroenterol 41:418–424 Phukan RK, Zomawia E, Narain K, Hazarika NC, Mahanta J (2005) Tobacco use and stomach cancer in Mizoram, India. Cancer Epidemiol Biomark Prev 14:1892–1896 Piazuelo MB, Correa P (2013) Gastric cáncer: overview. Colomb Med (Cali) 44(3):192–201 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):285–291 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 129:537–549 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 99:463–474 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):150–157 Santarelli RL, Pierre F, Corpet DE (2008) Processed meat and colorectal cancer: a review of epidemiologic and experimental evidence. Nutr Cancer 60(2):131–144 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):4815–4828 Shiohara M, Deiry WE, Wada M, Nakamaki T, Takeuchi S, Yang R (1994) Absence of WAF1 mutations in a variety of human malignancies. Nature 84:3781–3784 Stepanov I, Hecht SS, Ramakrishnan S, Gupta PC (2005) Tobacco-specific nitrosamines in smokeless tobacco products marketed in India. Int J Cancer 116(1):16–19 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):66–73 Sumathi B, Ramalingam S, Navaneethan U, Jayanthi V (2009) Risk factors for GC in South India. Singap Med J 50:147–151 Torre L, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global Cancer Statistics, 2012. CA Cancer J Clin 65:87–108 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 122:211–219 Tsugane S, Sasazuki S (2007) Diet and the risk of GC: review of epidemiological evidence. Gastric Cancer 10:75–83 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 90:128–134 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 443:821–828 Ward MH, Lopez-Carrillo L (1999) Dietary factors and the risk of GC in Mexico City. Am J Epidemiol 149:925–392 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 1263:275–280 Yaghoobi M, Bijarchi R, Narod SA (2010) Family history and the risk of GC. Br J Cancer 102(2):237–242 Yan L, Fang L, Sha Z, Suqing S, Li L, Lifeng L (2015) Genetics and GC susceptibility. Int J Clin Exp Med 8(6):8377–8383 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 124:157–166