Advertisement

Epigenetic Alterations in Stomach Cancer: Implications for Diet and Nutrition

  • Carolina Oliveira GigekEmail author
  • Elizabeth Suchi Chen
  • Marilia Arruda Cardoso Smith
Reference work entry

Abstract

Cancer is a malignant disease that involves a combination of genetic and epigenetic events along with external risk factors. Regarding stomach cancer, the risk factors include infections by Helicobacter pylori and by Epstein-Barr virus besides lifestyle habits, such as tobacco smoking, alcohol consumption, and high salt and low fruit and vegetable intakes. The stomach is one of the most predisposed organs to suffer aberrant epigenetic marks. Described alterations in stomach cancer comprise DNA methylation, histone marks, microRNA, and even enzymes involved in the epigenetic mechanisms. The relationship between cancer and diet is long established, and some nutrients can have a direct impact in the epigenetic of a cell, promoting or preventing gastric carcinogenesis. Intake of methionine, folate, polyphenols, alcohol, antioxidants such as curcumin and cranberries, and salty food has been shown to have an influence on the stomach tissue.

Keywords

Stomach cancer Gastric cancer Epigenetics DNA methylation Histone acetylation microRNA Folate Methionine Curcumin Resveratrol Green tea Cruciferous Vegetables 

List of Abbreviations

ARID1A

AT-rich interactive domain-containing protein 1A

BMP8B

Bone morphogenetic protein 8B

Cdc2

Cell division cycle protein 2 homolog

CDH1

E-cadherin

CDKN2A

Cyclin-dependent kinase inhibitor 2A

CDX2

Caudal type homeobox 2

CpG

5′- Citosine-phosphate-guanine-3′

DIM

3,3′-Diindolylmethane

DNA

Deoxyribonucleic acid

DNMT

DNA methyltransferase

EBV

Epstein-Barr virus

FLNC

Filamin-2

HAND1

Heart- and neural crest derivatives-expressed protein 1

HAT

Histone acetyltransferases

HDAC

Histone deacetylases

HDGC

Hereditary diffuse gastric cancer

HMT

Histone methyltransferase

IARC

International Agency for Research on Cancer

K

Lysine

MeCP2

Methyl-CpG-binding protein 2

miRNA

Micro-ribonucleic acid

MLH1

MutL homolog 1

mRNA

Messenger ribonucleic acid

NF-kB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NO

Nitric oxide

oncomiR

Oncogenic miRNA

p53

Protein P53

PTEN

Phosphatase and tensin homolog

R

Arginine

ROS

Reactive oxygen species

RUNX3

Runt-related transcription factor 3

SAH

S-adenosyl-L-homocysteine

SAM

S-Adenosyl-L-methionine

SIRT1

Sirtuin 1

TFF2

Trefoil factor 2

TREX1

Three prime repair exonuclease 1

TSA

Trichostatin A

tsmiR

Tumor suppressor miRNA

References

  1. Alkan A, Mizrak D, Utkan G (2015) Lower folate levels in gastric cancer: is it a cause or a result? World J Gastroenterol 21:4101–4102.  https://doi.org/10.3748/wjg.v21.i13.4101CrossRefPubMedPubMedCentralGoogle Scholar
  2. Angrisano T, Lembo F, Peluso S, Keller S, Chiariotti L, Pero R (2012) Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells. Med Microbiol Immunol 201:249–257.  https://doi.org/10.1007/s00430-011-0227-9CrossRefPubMedGoogle Scholar
  3. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB (2002) Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis 23:143–150CrossRefGoogle Scholar
  4. Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B et al (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209CrossRefGoogle Scholar
  5. Boveri T (1914) Zur Frage der Entstehung maligner Tumoren. English translation: The Origin of Malignant Tumors (1929) by Bovery, M. (Williams and Wilkins, Baltimore: 1929, 1914). Gustav Fischer Verlag, JenaGoogle Scholar
  6. Calcagno DQ, Gigek CO, Chen ES, Burbano RR, Smith Mde A (2012) DNA and histone methylation in gastric carcinogenesis. World J Gastroenterol 19:1182–1192CrossRefGoogle Scholar
  7. Cavuoto P, Fenech MF (2012) A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev 38:726–736.  https://doi.org/10.1016/j.ctrv.2012.01.004CrossRefPubMedGoogle Scholar
  8. Cogliano VJ, Baan R, Straif K, Grosse Y, Lauby-Secretan B, El Ghissassi F et al (2011) Preventable exposures associated with human cancers. J Natl Cancer Inst 103:1827–1839.  https://doi.org/10.1093/jnci/djr483CrossRefPubMedPubMedCentralGoogle Scholar
  9. Corso G, Carvalho J, Marrelli D, Vindigni C, Carvalho B, Seruca R et al (2013) Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. J Clin Oncol 31:868–875.  https://doi.org/10.1200/JCO.2012.44.4612CrossRefPubMedGoogle Scholar
  10. Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS et al (2015) Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med 21:449–456.  https://doi.org/10.1038/nm.3850CrossRefPubMedGoogle Scholar
  11. da Silva Oliveira KC, Thomaz Araujo TM, Albuquerque CI, Barata GA, Gigek CO, Leal MF et al (2016) Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer. World J Gastroenterol 22:7951–7962.  https://doi.org/10.3748/wjg.v22.i35.7951CrossRefPubMedPubMedCentralGoogle Scholar
  12. Davis CD, Uthus EO (2004) DNA methylation, cancer susceptibility, and nutrient interactions. Exp Biol Med (Maywood) 229:988–995CrossRefGoogle Scholar
  13. De R, Kundu P, Swarnakar S, Ramamurthy T, Chowdhury A, Nair GB et al (2009) Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice. Antimicrob Agents Chemother 53:1592–1597.  https://doi.org/10.1128/AAC.01242-08CrossRefPubMedPubMedCentralGoogle Scholar
  14. Del Prete A, Allavena P, Santoro G, Fumarulo R, Corsi MM, Mantovani A (2011) Molecular pathways in cancer-related inflammation. Biochem Med (Zagreb) 21:264–275CrossRefGoogle Scholar
  15. Deng W, Yang H, Wang J, Cai J, Bai Z, Song J et al (2016) Coffee consumption and the risk of incident gastric cancer – a meta-analysis of prospective cohort studies. Nutr Cancer 68:40–47.  https://doi.org/10.1080/01635581.2016.1115093CrossRefPubMedGoogle Scholar
  16. Ding SZ, Fischer W, Kaparakis-Liaskos M, Liechti G, Merrell DS, Grant PA et al (2010) Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS One 5:e9875.  https://doi.org/10.1371/journal.pone.0009875CrossRefPubMedPubMedCentralGoogle Scholar
  17. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21–33.  https://doi.org/10.1038/nrg1748CrossRefPubMedGoogle Scholar
  18. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al (2013) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. Retrieved 11/20/2016, 2016, from http://globocan.iarc.fr. doi
  19. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386.  https://doi.org/10.1002/ijc.29210CrossRefPubMedPubMedCentralGoogle Scholar
  20. Friso S, Udali S, De Santis D, Choi SW (2016) One-carbon metabolism and epigenetics. Mol Asp Med.  https://doi.org/10.1016/j.mam.2016.11.007
  21. Gao S, Ding LH, Wang JW, Li CB, Wang ZY (2013) Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate reductase in association with the susceptibility to gastric cancer. Asian Pac J Cancer Prev 14:299–302CrossRefGoogle Scholar
  22. Gigek CO, Chen ES, Calcagno DQ, Wisnieski F, Burbano RR, Smith MA (2012) Epigenetic mechanisms in gastric cancer. Epigenomics 4:279–294.  https://doi.org/10.2217/epi.12.22CrossRefPubMedGoogle Scholar
  23. Gigek CO, Chen ES, Smith MA (2015) Methyl-Cpg-Binding Protein (MBD) family: epigenomic read-outs functions and roles in tumorigenesis and psychiatric diseases. J Cell Biochem. doiGoogle Scholar
  24. Gonzalez CA, Agudo A (2011) Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go. Int J Cancer 130:745–753CrossRefGoogle Scholar
  25. Graziosi L, Mencarelli A, Renga B, D’Amore C, Bruno A, Santorelli C et al (2012) Epigenetic modulation by methionine deficiency attenuates the potential for gastric cancer cell dissemination. J Gastrointest Surg 17:39–49; discussion p 49.  https://doi.org/10.1007/s11605-012-1996-1
  26. Halpern BC, Clark BR, Hardy DN, Halpern RM, Smith RA (1974) The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture. Proc Natl Acad Sci U S A 71:1133–1136CrossRefGoogle Scholar
  27. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRefGoogle Scholar
  28. Holian O, Wahid S, Atten MJ, Attar BM (2002) Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric oxide. Am J Physiol Gastrointest Liver Physiol 282:G809–G816.  https://doi.org/10.1152/ajpgi.00193.2001CrossRefPubMedGoogle Scholar
  29. Kang Y, Hu W, Bai E, Zheng H, Liu Z, Wu J et al (2016) Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFkappaB survival-signaling pathway. Onco Targets Ther 9:7373–7384.  https://doi.org/10.2147/OTT.S118272CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kaurah P, Huntsman DG (2014) GeneReviews: hereditary diffuse gastric cancer. University of Washington, SeattleGoogle Scholar
  31. Khayat AS, Guimarães AC, Calcagno DQ, Seabra AD, Lima EM, Leal MF, et al (2009) Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinomaGoogle Scholar
  32. Kresty LA, Clarke J, Ezell K, Exum A, Howell AB, Guettouche T (2011) MicroRNA alterations in Barrett’s esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: insights for chemoprevention. J Carcinog 10:34.  https://doi.org/10.4103/1477-3163.91110CrossRefPubMedPubMedCentralGoogle Scholar
  33. Lauren P (1965) The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64:31–49CrossRefGoogle Scholar
  34. Lee TY, Chiang EP, Shih YT, Lane HY, Lin JT, Wu CY (2014) Lower serum folate is associated with development and invasiveness of gastric cancer. World J Gastroenterol 20:11313–11320.  https://doi.org/10.3748/wjg.v20.i32.11313CrossRefPubMedPubMedCentralGoogle Scholar
  35. Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS et al (2016) Association between helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology 150:1113–1124.e5.  https://doi.org/10.1053/j.gastro.2016.01.028CrossRefPubMedGoogle Scholar
  36. Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S et al (2013) Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology 145:554–565.  https://doi.org/10.1053/j.gastro.2013.05.010CrossRefPubMedGoogle Scholar
  37. Liu M, Lin LQ, Song BB, Wang LF, Zhang CP, Zhao JL et al (2009) Cranberry phytochemical extract inhibits SGC-7901 cell growth and human tumor xenografts in Balb/c nu/nu mice. J Agric Food Chem 57:762–768.  https://doi.org/10.1021/jf802780kCrossRefPubMedGoogle Scholar
  38. Liu X, Sun K, Song A, Zhang X, Zhang X, He X (2014) Curcumin inhibits proliferation of gastric cancer cells by impairing ATP-sensitive potassium channel opening. World J Surg Oncol 12:389.  https://doi.org/10.1186/1477-7819-12-389CrossRefPubMedPubMedCentralGoogle Scholar
  39. Ma SH, Jung W, Weiderpass E, Jang J, Hwang Y, Ahn C et al (2015) Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status. Br J Cancer 113:1381–1388.  https://doi.org/10.1038/bjc.2015.333CrossRefPubMedPubMedCentralGoogle Scholar
  40. Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M et al (2006) High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 12:989–995.  https://doi.org/10.1158/1078-0432.CCR-05-2096CrossRefPubMedGoogle Scholar
  41. McCay CM, Crowell MF, Maynard LA (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5:155–171; discussion 72PubMedGoogle Scholar
  42. McLean MH, El-Omar EM (2014) Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 11:664–674.  https://doi.org/10.1038/nrgastro.2014.143CrossRefPubMedGoogle Scholar
  43. Mello AA, Leal MF, Rey JA, Pinto GR, Lamarao LM, Montenegro RC et al (2015) Deregulated expression of SRC, LYN and CKB kinases by DNA methylation and its potential role in gastric cancer invasiveness and metastasis. PLoS One 10:e0140492.  https://doi.org/10.1371/journal.pone.0140492CrossRefPubMedPubMedCentralGoogle Scholar
  44. Moreira-Nunes CA, Barros MB, do Nascimento Borges B, Montenegro RC, Lamarao LM, Ribeiro HF et al (2014) Genetic screening analysis of patients with hereditary diffuse gastric cancer from northern and northeastern Brazil. Hered Cancer Clin Pract 12:18.  https://doi.org/10.1186/1897-4287-12-18CrossRefPubMedPubMedCentralGoogle Scholar
  45. Mu LN, Cao W, Zhang ZF, Yu SZ, Jiang QW, You NC et al (2007) Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer. Biomarkers 12:61–75.  https://doi.org/10.1080/13547500600945101CrossRefPubMedGoogle Scholar
  46. Nagini S (2012) Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 4:156–169.  https://doi.org/10.4251/wjgo.v4.i7.156CrossRefPubMedPubMedCentralGoogle Scholar
  47. Nanjo S, Asada K, Yamashita S, Nakajima T, Nakazawa K, Maekita T et al (2012) Identification of gastric cancer risk markers that are informative in individuals with past H. pylori infection. Gastric Cancer 15:382–388.  https://doi.org/10.1007/s10120-011-0126-1CrossRefPubMedGoogle Scholar
  48. Nardone G, Compare D (2008) Epigenetic alterations due to diet and Helicobacter pylori infection in gastric carcinogenesis. Expert Rev Gastroenterol Hepatol 2:243–248.  https://doi.org/10.1586/17474124.2.2.243CrossRefPubMedGoogle Scholar
  49. Pontes TB, Chen ES, Gigek CO, Calcagno DQ, Wisnieski F, Leal MF et al (2014) Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis. Tumour Biol 35:3447–3453.  https://doi.org/10.1007/s13277-013-1455-yCrossRefPubMedGoogle Scholar
  50. Rocco A, Nardone G (2007) Diet, H pylori infection and gastric cancer: evidence and controversies. World J Gastroenterol 13:2901–2912CrossRefGoogle Scholar
  51. Romanoski CE, Glass CK, Stunnenberg HG, Wilson L, Almouzni G (2015) Epigenomics: roadmap for regulation. Nature 518:314–316.  https://doi.org/10.1038/518314aCrossRefPubMedGoogle Scholar
  52. Saif MW, Makrilia N, Zalonis A, Merikas M, Syrigos K (2010) Gastric cancer in the elderly: an overview. Eur J Surg Oncol 36:709–717.  https://doi.org/10.1016/j.ejso.2010.05.023CrossRefPubMedGoogle Scholar
  53. Sanikini H, Dik VK, Siersema PD, Bhoo-Pathy N, Uiterwaal CS, Peeters PH et al (2015) Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: results from the EPIC cohort study. Int J Cancer 136:E720–E730.  https://doi.org/10.1002/ijc.29223CrossRefPubMedGoogle Scholar
  54. Sarkar A, De R, Mukhopadhyay AK (2016) Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases. World J Gastroenterol 22:2736–2748.  https://doi.org/10.3748/wjg.v22.i9.2736CrossRefPubMedPubMedCentralGoogle Scholar
  55. Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC (2006) Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res 66:1277–1281.  https://doi.org/10.1158/0008-5472.CAN-05-3632CrossRefPubMedGoogle Scholar
  56. Shimazu T, Asada K, Charvat H, Kusano C, Otake Y, Kakugawa Y et al (2015) Association of gastric cancer risk factors with DNA methylation levels in gastric mucosa of healthy Japanese: a cross-sectional study. Carcinogenesis 36:1291–1298.  https://doi.org/10.1093/carcin/bgv125CrossRefPubMedGoogle Scholar
  57. Stefanska B, Karlic H, Varga F, Fabianowska-Majewska K, Haslberger A (2012) Epigenetic mechanisms in anti-cancer actions of bioactive food components – the implications in cancer prevention. Br J Pharmacol 167:279–297.  https://doi.org/10.1111/j.1476-5381.2012.02002.xCrossRefPubMedPubMedCentralGoogle Scholar
  58. Sun Q, Zhang W, Guo Y, Li Z, Chen X, Wang Y et al (2016) Curcumin inhibits cell growth and induces cell apoptosis through upregulation of miR-33b in gastric cancer. Tumour Biol 37:13177–13184.  https://doi.org/10.1007/s13277-016-5221-9CrossRefPubMedGoogle Scholar
  59. Tahara T, Arisawa T (2015) DNA methylation as a molecular biomarker in gastric cancer. Epigenomics 7:475–486.  https://doi.org/10.2217/epi.15.4CrossRefPubMedGoogle Scholar
  60. Tio M, Andrici J, Cox MR, Eslick GD (2014) Folate intake and the risk of upper gastrointestinal cancers: a systematic review and meta-analysis. J Gastroenterol Hepatol 29:250–258.  https://doi.org/10.1111/jgh.12446CrossRefPubMedGoogle Scholar
  61. Wadhwa R, Song S, Lee JS, Yao Y, Wei Q, Ajani JA (2014) Gastric cancer-molecular and clinical dimensions. Nat Rev Clin Oncol 10:643–655CrossRefGoogle Scholar
  62. Weh KM, Clarke J, Kresty LA (2016) Cranberries and cancer: an update of preclinical studies evaluating the cancer inhibitory potential of cranberry and cranberry derived constituents. Antioxidants (Basel) 5:27.  https://doi.org/10.3390/antiox5030027CrossRefGoogle Scholar
  63. Wisnieski F, Calcagno DQ, Leal MF, Chen ES, Gigek CO, Santos LC et al (2014) Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A. Tumour Biol 35:6373–6381.  https://doi.org/10.1007/s13277-014-1841-0CrossRefPubMedGoogle Scholar
  64. Wisnieski F, Calcagno DQ, Leal MF, Santos LC, Gigek CO, Chen ES et al (2015) CDKN1A histone acetylation and gene expression relationship in gastric adenocarcinomas. Clin Exp Med 17:121–129.  https://doi.org/10.1007/s10238-015-0400-3CrossRefPubMedGoogle Scholar
  65. Wisnieski F, Leal MF, Calcagno DQ, Santos LC, Gigek CO, Chen ES et al (2016) BMP8B is a tumor suppressor gene regulated by histone acetylation in gastric cancer. J Cell Biochem.  https://doi.org/10.1002/jcb.25766
  66. Wu WK, Yu J, Chan MT, To KF, Cheng AS (2016) Combinatorial epigenetic deregulation by Helicobacter pylori and Epstein-Barr virus infections in gastric tumourigenesis. J Pathol 239:245–249.  https://doi.org/10.1002/path.4731CrossRefPubMedGoogle Scholar
  67. Yang Q, Wang B, Zang W, Wang X, Liu Z, Li W et al (2013) Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner. PLoS One 8:e70627.  https://doi.org/10.1371/journal.pone.0070627CrossRefPubMedPubMedCentralGoogle Scholar
  68. Ye Y, Fang Y, Xu W, Wang Q, Zhou J, Lu R (2016) 3,3′-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy. Biochem Pharmacol 115:77–84.  https://doi.org/10.1016/j.bcp.2016.06.018CrossRefPubMedGoogle Scholar
  69. Yuasa Y, Nagasaki H, Akiyama Y, Sakai H, Nakajima T, Ohkura Y et al (2005) Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients. Carcinogenesis 26:193–200.  https://doi.org/10.1093/carcin/bgh304CrossRefPubMedGoogle Scholar
  70. Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K et al (2009) DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients. Int J Cancer 124:2677–2682.  https://doi.org/10.1002/ijc.24231CrossRefPubMedGoogle Scholar
  71. Zaridze D, Borisova E, Maximovitch D, Chkhikvadze V (2000) Alcohol consumption, smoking and risk of gastric cancer: case-control study from Moscow, Russia. Cancer Causes Control 11:363–371CrossRefGoogle Scholar
  72. Zhang L, Ma J, Pan K, Go VL, Chen J, You WC (2005) Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter 10:139–145.  https://doi.org/10.1111/j.1523-5378.2005.00301.xCrossRefPubMedGoogle Scholar
  73. Zhu H, Li X, Zhang X, Chen D, Li D, Ren J et al (2016) Polymorphisms in mismatch repair genes are associated with risk and microsatellite instability of gastric cancer, and interact with life exposures. Gene 579:52–57.  https://doi.org/10.1016/j.gene.2015.12.050CrossRefPubMedGoogle Scholar
  74. Zou P, Xia Y, Chen T, Zhang J, Wang Z, Chen W et al (2016) Selective killing of gastric cancer cells by a small molecule targeting ROS-mediated ER stress activation. Mol Carcinog 55:1073–1086.  https://doi.org/10.1002/mc.22351CrossRefPubMedGoogle Scholar
  75. Zulueta A, Caretti A, Signorelli P, Ghidoni R (2015) Resveratrol: a potential challenger against gastric cancer. World J Gastroenterol 21:10636–10643.  https://doi.org/10.3748/wjg.v21.i37.10636CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Carolina Oliveira Gigek
    • 1
    • 2
    Email author
  • Elizabeth Suchi Chen
    • 1
  • Marilia Arruda Cardoso Smith
    • 1
  1. 1.Division of Genetics, Department of Morphology and GeneticsUniversidade Federal de São Paulo (UNIFESP)São PauloBrazil
  2. 2.Division of Surgical Gastroenterology, Department of SurgeryUniversidade Federal de São Paulo (UNIFESP)São PauloBrazil

Personalised recommendations