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Ornithine decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus

Oncogene volume 40, pages 5963–5969 (2021)Cite this article

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Abstract

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer in univariate models as well as models adjusted for age, sex, and CagA serostatus. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10−3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the T allele at rs1927914.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8:e180–e90.

    Article  PubMed  Google Scholar 

  3. Torres J, Correa P, Ferreccio C, Hernandez-Suarez G, Herrero R, Cavazza-Porro M, et al. Gastric cancer incidence and mortality is associated with altitude in the mountainous regions of Pacific Latin America. Cancer Cause Control. 2013;24:249–56.

    Article  Google Scholar 

  4. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet .2018;391:1023–75.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kodaman N, Pazos A, Schneider BG, Piazuelo MB, Mera R, Sobota RS, et al. Human and Helicobacter pylori coevolution shapes the risk of gastric disease. Proc Natl Acad Sci U.S.A. 2014;111:1455–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bonequi P, Meneses-Gonzalez F, Correa P, Rabkin CS, Camargo MC. Risk factors for gastric cancer in Latin America: a meta-analysis. Cancer Causes Control. 2013;24:217–31.

    Article  PubMed  Google Scholar 

  7. Miller KD, Goding Sauer A, Ortiz AP, Fedewa SA, Pinheiro PS, Tortolero-Luna G, et al. Cancer statistics for hispanics/latinos, 2018. CA Cancer J Clin. 2018;68:425–45.

    Article  PubMed  Google Scholar 

  8. Pabla BS, Shah SC, Corral JE, Morgan DR. Increased incidence and mortality of gastric cancer in immigrant populations from high to low regions of incidence: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2020;18:347–59.

    Article  PubMed  Google Scholar 

  9. Correa P. Helicobacter pylori and gastric cancer: state of the art. Cancer Epidemiol Biomark Prev. 1996;5:477–81.

    CAS  Google Scholar 

  10. Venerito M, Vasapolli R, Rokkas T, Malfertheiner P. Gastric cancer: epidemiology, prevention, and therapy. Helicobacter.2018;23:e12518.

    Article  PubMed  CAS  Google Scholar 

  11. Burucoa C, Axon A. Epidemiology of Helicobacter pylori infection. Helicobacter.2017;22:1.

    Article  Google Scholar 

  12. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature.2000;404:398–402.

    Article  CAS  PubMed  Google Scholar 

  13. Tavera G, Morgan DR, Williams SM. Tipping the scale toward gastric disease: a host-pathogen genomic mismatch? Curr Genet Med Rep. 2018;6:199–207.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kupfer SS. Gaining ground in the genetics of gastric cancer. Gastroenterology.2017;152:926–8.

    Article  PubMed  Google Scholar 

  15. Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, et al. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55:2111–5.

    CAS  PubMed  Google Scholar 

  16. El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology.2003;124:1193–201.

    Article  CAS  PubMed  Google Scholar 

  17. Tian J, Liu G, Zuo C, Liu C, He W, Chen H. Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies. Cancer Biol Med. 2019;16:361–89.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, et al. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet. 2010;42:764–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Study Group of Millennium Genome Project for C, Sakamoto H, Yoshimura K, Saeki N, Katai H, Shimoda T, et al. Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet. 2008;40:730–40.

    Article  CAS  Google Scholar 

  20. Shi Y, Hu Z, Wu C, Dai J, Li H, Dong J, et al. A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet.2011;43:1215–8.

    Article  CAS  PubMed  Google Scholar 

  21. Song HR, Kim HN, Kweon SS, Choi JS, Shim HJ, Cho SH, et al. Genetic variations in the PRKAA1 and ZBTB20 genes and gastric cancer susceptibility in a Korean population. Mol Carcinog. 2013;52:E155–60.

    Article  CAS  PubMed  Google Scholar 

  22. Gonzalez-Hormazabal P, Retamales-Ortega R, Musleh M, Bustamante M, Stambuk J, Pisano R, et al. Polymorphisms PSCA rs2294008, IL-4 rs2243250 and MUC1 rs4072037 are associated with gastric cancer in a high risk population. Mol Biol Rep. 2020;47:9239–43.

    Article  CAS  PubMed  Google Scholar 

  23. Snaith A, El-Omar EM. Helicobacter pylori: host genetics and disease outcomes. Expert Rev Gastroenterol Hepatol. 2008;2:577–85.

    Article  CAS  PubMed  Google Scholar 

  24. Kodaman N, Sobota RS, Mera R, Schneider BG, Williams SM. Disrupted human-pathogen co-evolution: a model for disease. Front Genet. 2014;5:290.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Pegg AE. Regulation of ornithine decarboxylase. J Biol Chem. 2006;281:14529–32.

    Article  CAS  PubMed  Google Scholar 

  26. Asim M, Chaturvedi R, Hoge S, Lewis ND, Singh K, Barry DP, et al. Helicobacter pylori induces ERK-dependent formation of a phospho-c-Fos c-Jun activator protein-1 complex that causes apoptosis in macrophages. J Biol Chem. 2010;285:20343–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pegg AE. Mammalian polyamine metabolism and function. IUBMB Life. 2009;61:880–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zell JA, McLaren CE, Chen WP, Thompson PA, Gerner EW, Meyskens FL. Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients. J Natl Cancer Inst. 2010;102:1513–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Martinez ME, O’Brien TG, Fultz KE, Babbar N, Yerushalmi H, Qu N, et al. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci U.S.A. 2003;100:7859–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hardbower DM, Asim M, Luis PB, Singh K, Barry DP, Yang C, et al. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. Proc Natl Acad Sci U.S.A. 2017;114:E751–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cheng Y, Chaturvedi R, Asim M, Bussiere FI, Scholz A, Xu H, et al. Helicobacter pylori-induced macrophage apoptosis requires activation of ornithine decarboxylase by c-Myc. J Biol Chem. 2005;280:22492–6.

    Article  CAS  PubMed  Google Scholar 

  32. Cho LY, Yang JJ, Ko KP, Ma SH, Shin A, Choi BY, et al. Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations. Gastric Cancer. 2015;18:495–503.

    Article  CAS  PubMed  Google Scholar 

  33. Morgan DR, Dominguez RL, Keku TO, Heidt PE, Martin CF, Galanko JA, et al. Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras. Clin Gastroenterol Hepatol. 2006;4:1103–11.

    Article  CAS  PubMed  Google Scholar 

  34. Cai H, Ye F, Michel A, Murphy G, Sasazuki S, Taylor PR, et al. Helicobacter pylori blood biomarker for gastric cancer risk in East Asia. Int J Epidemiol. 2016;45:774–81.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Parsonnet J, Friedman GD, Orentreich N, Vogelman H. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut.1997;40:297–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gao L, Weck MN, Michel A, Pawlita M, Brenner H. Association between chronic atrophic gastritis and serum antibodies to 15 Helicobacter pylori proteins measured by multiplex serology. Cancer Res. 2009;69:2973–80.

    Article  CAS  PubMed  Google Scholar 

  37. Weck MN, Gao L, Brenner H. Helicobacter pylori infection and chronic atrophic gastritis: associations according to severity of disease. Epidemiology.2009;20:569–74.

    Article  PubMed  Google Scholar 

  38. Epplein M, Zheng W, Xiang YB, Peek RM Jr., Li H, Correa P, et al. Prospective study of Helicobacter pylori biomarkers for gastric cancer risk among Chinese men. Cancer Epidemiol Biomark Prev. 2012;21:2185–92.

    Article  CAS  Google Scholar 

  39. Michel A, Waterboer T, Kist M, Pawlita M. Helicobacter pylori multiplex serology. Helicobacter.2009;14:525–35.

    Article  CAS  PubMed  Google Scholar 

  40. Hardbower DM, Peek RM Jr., Wilson KT. At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer. J Leukoc Biol. 2014;96:201–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Zambon CF, Basso D, Navaglia F, Belluco C, Falda A, Fogar P, et al. Pro- and anti-inflammatory cytokines gene polymorphisms and Helicobacter pylori infection: interactions influence outcome. Cytokine.2005;29:141–52.

    Article  CAS  PubMed  Google Scholar 

  42. Hardbower DM, de Sablet T, Chaturvedi R, Wilson KT. Chronic inflammation and oxidative stress: the smoking gun for Helicobacter pylori-induced gastric cancer? Gut Microbes. 2013;4:475–81.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kim JJ, Tao H, Carloni E, Leung WK, Graham DY, Sepulveda AR. Helicobacter pylori impairs DNA mismatch repair in gastric epithelial cells. Gastroenterology.2002;123:542–53.

    Article  CAS  PubMed  Google Scholar 

  44. Kavermann H, Burns BP, Angermuller K, Odenbreit S, Fischer W, Melchers K, et al. Identification and characterization of Helicobacter pylori genes essential for gastric colonization. J Exp Med. 2003;197:813–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest. 2007;117:60–9.

    Article  CAS  PubMed  Google Scholar 

  46. Mondaca S, Yaeger R. Colorectal cancer genomics and designing rational trials. Ann Transl Med. 2018;6:159.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Zell JA, Ziogas A, Ignatenko N, Honda J, Qu N, Bobbs AS, et al. Associations of a polymorphism in the ornithine decarboxylase gene with colorectal cancer survival. Clin Cancer Res. 2009;15:6208–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jensen KH, Izarzugaza JMG, Juncker AS, Hansen RB, Hansen TF, Timshel P, et al. Analysis of a gene panel for targeted sequencing of colorectal cancer samples. Oncotarget.2018;9:9043–60.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Park JY, Forman D, Waskito LA, Yamaoka Y, Crabtree JE. Epidemiology of Helicobacter pylori and CagA-Positive infections and global variations in gastric cancer. Toxins (Basel). 2018;10:163.

    Article  CAS  Google Scholar 

  50. Pormohammad A, Ghotaslou R, Leylabadlo HE, Nasiri MJ, Dabiri H, Hashemi A. Risk of gastric cancer in association with Helicobacter pylori different virulence factors: a systematic review and meta-analysis. Micro Pathog. 2018;118:214–9.

    Article  Google Scholar 

  51. Jakszyn P, Bingham S, Pera G, Agudo A, Luben R, Welch A, et al. Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European prospective investigation into cancer and nutrition (EPIC-EURGAST) study. Carcinogenesis.2006;27:1497–501.

    Article  CAS  PubMed  Google Scholar 

  52. Haley KP, Gaddy JA. Nutrition and Helicobacter pylori: host diet and nutritional immunity influence bacterial virulence and disease outcome. Gastroenterol Res Pr. 2016;2016:3019362.

    Google Scholar 

  53. La Torre G, Chiaradia G, Gianfagna F, De Lauretis A, Boccia S, Mannocci A, et al. Smoking status and gastric cancer risk: an updated meta-analysis of case-control studies published in the past ten years. Tumori.2009;95:13–22.

    Article  PubMed  Google Scholar 

  54. Bonder MJ, Kurilshikov A, Tigchelaar EF, Mujagic Z, Imhann F, Vila AV, et al. The effect of host genetics on the gut microbiome. Nat Genet. 2016;48:1407–12.

    Article  CAS  PubMed  Google Scholar 

  55. Kurilshikov A, Wijmenga C, Fu J, Zhernakova A. Host genetics and gut microbiome: challenges and perspectives. Trends Immunol. 2017;38:633–47.

    Article  CAS  PubMed  Google Scholar 

  56. Kolde R, Franzosa EA, Rahnavard G, Hall AB, Vlamakis H, Stevens C, et al. Host genetic variation and its microbiome interactions within the Human Microbiome Project. Genome Med. 2018;10:6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Singh K, Coburn LA, Asim M, Barry DP, Allaman MM, Shi C, et al. Ornithine decarboxylase in macrophages exacerbates colitis and promotes colitis-associated colon carcinogenesis by impairing M1 immune responses. Cancer Res. 2018;78:4303–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hardbower DM, Coburn LA, Asim M, Singh K, Sierra JC, Barry DP, et al. EGFR-mediated macrophage activation promotes colitis-associated tumorigenesis. Oncogene.2017;36:3807–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sierra JC, Suarez G, Piazuelo MB, Luis PB, Baker DR, Romero-Gallo J, et al. alpha-Difluoromethylornithine reduces gastric carcinogenesis by causing mutations in Helicobacter pylori cagY. Proc Natl Acad Sci U.S.A. 2019;116:5077–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chaturvedi R, de Sablet T, Asim M, Piazuelo MB, Barry DP, Verriere TG, et al. Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase. Oncogene.2015;34:3429–40.

    Article  CAS  PubMed  Google Scholar 

  61. Sierra JC, Piazuelo MB, Luis PB, Barry DP, Allaman MM, Asim M, et al. Spermine oxidase mediates Helicobacter pylori-induced gastric inflammation, DNA damage, and carcinogenic signaling. Oncogene.2020;39:4465–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Castano-Rodriguez N, Kaakoush NO, Goh KL, Fock KM, Mitchell HM. The NOD-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer: a case-control study and gene expression analyses. PLoS ONE. 2014;9:e98899.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Li X, Liu S, Luo J, Liu A, Tang S, Liu S, et al. Helicobacter pylori induces IL-1beta and IL-18 production in human monocytic cell line through activation of NLRP3 inflammasome via ROS signaling pathway. Pathog Dis. 2015;73:1–8.

    Article  PubMed  CAS  Google Scholar 

  64. Hitzler I, Sayi A, Kohler E, Engler DB, Koch KN, Hardt WD, et al. Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1beta and IL-18. J Immunol. 2012;188:3594–602.

    Article  CAS  PubMed  Google Scholar 

  65. Koch KN, Hartung ML, Urban S, Kyburz A, Bahlmann AS, Lind J, et al. Helicobacter urease-induced activation of the TLR2/NLRP3/IL-18 axis protects against asthma. J Clin Investig. 2015;125:3297–302.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yang JC, Yang HC, Shun CT, Wang TH, Chien CT, Kao JY. Catechins and sialic acid attenuate helicobacter pylori-triggered epithelial caspase-1 activity and eradicate helicobacter pylori infection. Evid Based Complement Altern Med. 2013;2013:248585.

    Google Scholar 

  67. Koch KN, Muller A. Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens. Gut Microbes. 2015;6:382–7.

    Article  CAS  PubMed  Google Scholar 

  68. Wilson KT, Crabtree JE. Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology.2007;133:288–308.

    Article  CAS  PubMed  Google Scholar 

  69. Peek RM Jr., Miller GG, Tham KT, Perez-Perez GI, Zhao X, Atherton JC, et al. Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains. Lab Invest. 1995;73:760–70.

    CAS  PubMed  Google Scholar 

  70. Rolig AS, Cech C, Ahler E, Carter JE, Ottemann KM. The degree of Helicobacter pylori-triggered inflammation is manipulated by preinfection host microbiota. Infect Immun. 2013;81:1382–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gong Y, Tao L, Jing L, Liu D, Hu S, Liu W, et al. Association of TLR4 and Treg in Helicobacter pylori Colonization and Inflammation in Mice. PLoS ONE. 2016;11:e0149629.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Smith SM. Role of Toll-like receptors in Helicobacter pylori infection and immunity. World J Gastrointest Pathophysiol. 2014;5:133–46.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Su B, Ceponis PJ, Lebel S, Huynh H, Sherman PM. Helicobacter pylori activates Toll-like receptor 4 expression in gastrointestinal epithelial cells. Infect Immun. 2003;71:3496–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wang TR, Peng JC, Qiao YQ, Zhu MM, Zhao D, Shen J, et al. Helicobacter pylori regulates TLR4 and TLR9 during gastric carcinogenesis. Int J Clin Exp Pathol. 2014;7:6950–5.

    PubMed  PubMed Central  Google Scholar 

  75. Takenaka R, Yokota K, Ayada K, Mizuno M, Zhao Y, Fujinami Y, et al. Helicobacter pylori heat-shock protein 60 induces inflammatory responses through the Toll-like receptor-triggered pathway in cultured human gastric epithelial cells. Microbiology.2004;150:3913–22.

    Article  CAS  PubMed  Google Scholar 

  76. Jin J, Lin F, Liao S, Bao Q, Ni L. Effects of SNPs (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C), smoking, and drinking on susceptibility to laryngeal cancer among Han Chinese. PloS ONE. 2014;9:e106580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Li W, Bao G, Chen W, Qiang X, Zhu S, Wang S, et al. Connexin 43 Hemichannel as a novel mediator of sterile and infectious inflammatory diseases. Sci Rep. 2018;8:166.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Terlizzi M, Molino A, Colarusso C, Donovan C, Imitazione P, Somma P, et al. Activation of the absent in melanoma 2 inflammasome in peripheral blood mononuclear cells from idiopathic pulmonary fibrosis patients leads to the release of pro-fibrotic mediators. Front Immunol. 2018;9:670.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Zhu Y, Zhu H, Wang Z, Gao F, Wang J, Zhang W. Wogonoside alleviates inflammation induced by traumatic spinal cord injury by suppressing NF-kappaB and NLRP3 inflammasome activation. Exp Ther Med. 2017;14:3304–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Dominguez RL, Crockett SD, Lund JL, Suazo LP, Heidt P, Martin C, et al. Gastric cancer incidence estimation in a resource-limited nation: use of endoscopy registry methodology. Cancer Causes Control. 2013;24:233–9.

    Article  PubMed  Google Scholar 

  81. Varga MG, Wood CR, Butt J, Ryan ME, Youe WC, Pane K, et al. Immunostimulatory membrane proteins potentiate H. pylori-induced carcinogenesis by enabling CagA translocation. Gut Microbes. 2021;13:E1862613.

    Article  CAS  Google Scholar 

  82. Butt J, Blot WJ, Shrubsole MJ, Waterboer T, Pawlita M, Epplein M. Differences in antibody levels to H. pylori virulence factors VacA and CagA among African Americans and whites in the Southeast USA. Cancer Causes Control. 2020;31:601–6.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, Shen H, et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res. 2010;20:440–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. A global reference for human genetic variation. Nature.2015;526:68–74.

    Article  CAS  Google Scholar 

  86. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics.2005;21:263–5.

    Article  CAS  PubMed  Google Scholar 

  87. Rowland M, Daly L, Vaughan M, Higgins A, Bourke B, Drumm B. Age-specific incidence of Helicobacter pylori. Gastroenterology. 2006;130:65–72.

    Article  PubMed  Google Scholar 

  88. de Martel C, Parsonnet J. Helicobacter pylori infection and gender: a meta-analysis of population-based prevalence surveys. Dig Dis Sci. 2006;51:2292–301.

    Article  PubMed  Google Scholar 

  89. Replogle ML, Glaser SL, Hiatt RA, Parsonnet J. Biologic sex as a risk factor for Helicobacter pylori infection in healthy young adults. Am J Epidemiol. 1995;142:856–63.

    Article  CAS  PubMed  Google Scholar 

  90. Camargo MC, Goto Y, Zabaleta J, Morgan DR, Correa P, Rabkin CS. Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev. 2012;21:20–38.

    Article  CAS  Google Scholar 

  91. Greene CS, Krishnan A, Wong AK, Ricciotti E, Zelaya RA, Himmelstein DS, et al. Understanding multicellular function and disease with human tissue-specific networks. Nat Genet. 2015;47:569–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We recognize our colleagues in the Hospital de Occidente, Honduras Ministry of Health, and Central America Medical Outreach (CAMO), with special thanks to Lesby Castellanos, Carmen Ramos, Kathy Tschiegg, and Dr. Lia Suazo. We acknowledge the contributions of Dr. Enrique Martinez (Hospital Evangelico, Honduras) and Dr. Michael Pawlita (DKFZ).

Funding

This study was funded in part by the U.S. National Cancer Institute (P01CA028842 (DRM, KTW, SMW), R01CA190612 (DRM, KTW), K07 CA125588 (DRM), PAR-15-155 (DRM), P30CA068485 (DRM, KTW), P01CA116087 (KTW)), Veterans Affairs Merit Review grant I01CX002171 (KTW), Department of Defense grant W81XWH-18-1-0301 (KTW), NIH T32HL007567 (AKM), and National Library of Medicine 1R01LM010098 (SMW). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the paper. SBR, RLD, RM, and DRM had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. DRM had final responsibility for the decision to submit for publication.

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Author notes

  1. These authors contributed equally: Anna K. Miller, Gloria Tavera, Scott M. Williams, Douglas R. Morgan.

Authors and Affiliations

  1. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA

    Anna K. Miller & Scott M. Williams

  2. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA

    Gloria Tavera & Scott M. Williams

  3. Hospital de Occidente, Ministry of Health, Santa Rosa de Copan, Copan, Honduras

    Ricardo L. Dominguez

  4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA

    M. Constanza Camargo

  5. Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Tim Waterboer

  6. Vanderbilt University Medical Center, Division of Gastroenterology, Hepatology, and Nutrition, Nashville, TN, USA

    Keith T. Wilson

  7. Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA

    Keith T. Wilson

  8. UAB Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham (UAB), Birmingham, AL, USA

    Douglas R. Morgan

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Contributions

Study concept and design: RLD, MCC, KTW, SMW, DRM. Data acquisition: RLD, TW, DRM. Analysis and interpretation of data: AKM, GT, MCC, SMW, DRM. Paper preparation: AKM, GT, SMW, DRM. Critical review: AKM, GT, RLD, MCC, TW, KTW, SMW, DRM.

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Correspondence to Scott M. Williams or Douglas R. Morgan.

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Miller, A.K., Tavera, G., Dominguez, R.L. et al. Ornithine decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus. Oncogene 40, 5963–5969 (2021). https://doi.org/10.1038/s41388-021-01981-5

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