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Cholera Vaccine Use Is Associated With a Reduced Risk of Death in Patients With Colorectal Cancer: A Population-Based Study

  • Jianguang Ji
    Correspondence
    Reprint requests Address requests for reprint to: Jianguang Ji, MD, PhD, Center for Primary Health Care Research, Jan Waldenströms gata 35, Skåne University Hospital, 205 02 Malmö, Sweden. tel.: +4640391382; fax: +4640391370.
    Affiliations
    Center for Primary Health Care Research, Lund University/Region Skåne, Sweden
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  • Jan Sundquist
    Affiliations
    Center for Primary Health Care Research, Lund University/Region Skåne, Sweden

    Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Kristina Sundquist
    Affiliations
    Center for Primary Health Care Research, Lund University/Region Skåne, Sweden

    Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
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Published:September 15, 2017DOI:https://doi.org/10.1053/j.gastro.2017.09.009

      Background & Aims

      Cholera toxin can act as a modulator of the immune response with anti-inflammatory effects; it reduces development of colon polyps in mouse models of colorectal cancer (CRC). We performed a population-based study to determine whether, in patients with a diagnosis of CRC, subsequent administration of the cholera vaccine (killed Vibrio cholerae O1 whole cells and recombinant cholera toxin B subunit) affects mortality.

      Methods

      We identified patients from the Swedish Cancer Register who were diagnosed with CRC from July 2005 through December 2012. These patients were linked to the Swedish Prescribed Drug Register to retrieve cholera vaccine use. We used Cox regression analysis to calculate the hazard ratio (HR) of death from CRC and overall mortality in patients with post-diagnostic use of cholera vaccine compared with matched controls.

      Results

      A total of 175 patients were diagnosed with CRC and given a prescription for the cholera vaccine after their cancer diagnosis. Compared with propensity score-matched controls and adjusted for confounding factors, patients with CRC who received the cholera vaccine had a decreased risk of death from CRC (HR, 0.53; 95% CI, 0.29–0.99) and a decreased risk of death overall (HR, 0.59; 95% CI, 0.37–0.94). The decrease in mortality with cholera vaccination was largely observed, irrespective of patient age or tumor stage at diagnosis or sex.

      Conclusions

      In a population-based study, we associated administration of the cholera vaccine after CRC diagnosis with decreased risk of death from CRC and overall mortality.

      Graphical abstract

      Keywords

      Abbreviations used in this paper:

      CI (confidence interval), CRC (colorectal cancer), CTA1 (cholera toxin A1), CTB (cholera toxin B), HR (hazard ratio)
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      References

        • Arnold M.
        • Sierra M.S.
        • Laversanne M.
        • et al.
        Global patterns and trends in colorectal cancer incidence and mortality.
        Gut. 2017; 66: 683-691
        • American Cancer Society
        Cancer Facts & Figures 2017.
        American Cancer Society, Atlanta, GA2017 (Available at:)
        • Jemal A.
        • Clegg L.X.
        • Ward E.
        • et al.
        Annual report to the nation on the status of cancer, 1975-2001, with a special feature regarding survival.
        Cancer. 2004; 101: 3-27
        • Ait Ouakrim D.
        • Pizot C.
        • Boniol M.
        • et al.
        Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database.
        BMJ. 2015; 351: h4970
        • Oikonomopoulou K.
        • Brinc D.
        • Kyriacou K.
        • et al.
        Infection and cancer: revaluation of the hygiene hypothesis.
        Clin Cancer Res. 2013; 19: 2834-2841
        • Baxter N.T.
        • Zackular J.P.
        • Chen G.Y.
        • et al.
        Structure of the gut microbiome following colonization with human feces determines colonic tumor burden.
        Microbiome. 2014; 2: 20
        • Zackular J.P.
        • Baxter N.T.
        • Iverson K.D.
        • et al.
        The gut microbiome modulates colon tumorigenesis.
        mBio. 2013; 4 (e00692–13)
        • Zackular J.P.
        • Baxter N.T.
        • Chen G.Y.
        • et al.
        Manipulation of the gut microbiota reveals role in colon tumorigenesis.
        mSphere. 2015; 1
        • Belcheva A.
        • Irrazabal T.
        • Robertson S.J.
        • et al.
        Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells.
        Cell. 2014; 158: 288-299
        • Doulberis M.
        • Angelopoulou K.
        • Kaldrymidou E.
        • et al.
        Cholera-toxin suppresses carcinogenesis in a mouse model of inflammation-driven sporadic colon cancer.
        Carcinogenesis. 2015; 36: 280-290
        • Poutahidis T.
        • Angelopoulou K.
        • Erdman S.E.
        Old enemies meet new friends for colon cancer prevention.
        Oncoimmunology. 2015; 4: e1027474
        • Baldauf K.J.
        • Royal J.M.
        • Kouokam J.C.
        • et al.
        Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.
        Mucosal Immunol. 2017; 10: 887-900
        • O'Keefe S.J.
        Diet, microorganisms and their metabolites, and colon cancer.
        Nat Rev Gastroenterol Hepatol. 2016; 13: 691-706
        • Ji J.
        • Sundquist K.
        • Sundquist J.
        • et al.
        Comparability of cancer identification among Death Registry, Cancer Registry and Hospital Discharge Registry.
        Int J Cancer. 2012; 131: 2085-2093
        • Liu X.
        • Ji J.
        • Sundquist K.
        • et al.
        The impact of type 2 diabetes mellitus on cancer-specific survival: a follow-up study in Sweden.
        Cancer. 2012; 118: 1353-1361
        • Hemminki K.
        • Santi I.
        • Weires M.
        • et al.
        Tumor location and patient characteristics of colon and rectal adenocarcinomas in relation to survival and TNM classes.
        BMC Cancer. 2010; 10: 688
        • Hamilton S.
        • Aaltonen L.
        Pathology and Genetics. Tumours of the digestive system. WHO Classification of Tumours. Colume 2.
        IARC, Lyon2000
        • Suissa S.
        Immortal time bias in pharmaco-epidemiology.
        Am J Epidemiol. 2008; 167: 492-499
        • Cavalli-Bjorkman N.
        • Lambe M.
        • Eaker S.
        • et al.
        Differences according to educational level in the management and survival of colorectal cancer in Sweden.
        Eur J Cancer. 2011; 47: 1398-1406
        • Akinyemiju T.
        • Meng Q.
        • Vin-Raviv N.
        Race/ethnicity and socio-economic differences in colorectal cancer surgery outcomes: analysis of the nationwide inpatient sample.
        BMC Cancer. 2016; 16: 715
        • Eek F.
        • Ostergren P.O.
        • Diderichsen F.
        • et al.
        Differences in socioeconomic and gender inequalities in tobacco smoking in Denmark and Sweden; a cross sectional comparison of the equity effect of different public health policies.
        BMC Publ Health. 2010; 10: 9
        • Ax E.
        • Warensjo Lemming E.
        • Becker W.
        • et al.
        Dietary patterns in Swedish adults; results from a national dietary survey.
        Br J Nutr. 2016; 115: 95-104
        • Lopez-Gigosos R.
        • Garcia-Fortea P.
        • Reina-Dona E.
        • et al.
        Effectiveness in prevention of travellers' diarrhoea by an oral cholera vaccine WC/rBS.
        Travel Med Infect Dis. 2007; 5: 380-384
        • Baldauf K.J.
        • Royal J.M.
        • Hamorsky K.T.
        • et al.
        Cholera toxin B: one subunit with many pharmaceutical applications.
        Toxins. 2015; 7: 974-996
        • Guo L.
        • Li X.
        • Tang F.
        • et al.
        Immunological features and the ability of inhibitory effects on enzymatic activity of an epitope vaccine composed of cholera toxin B subunit and B cell epitope from Helicobacter pylori urease A subunit.
        Appl Microbiol Biotechnol. 2012; 93: 1937-1945
        • Kono M.
        • Hotomi M.
        • Hollingshead S.K.
        • et al.
        Maternal immunization with pneumococcal surface protein A protects against pneumococcal infections among derived offspring.
        PloS One. 2011; 6: e27102
        • Matoba N.
        • Magerus A.
        • Geyer B.C.
        • et al.
        A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs.
        Proc Natl Acad Sci U S A. 2004; 101: 13584-13589
        • Zolla-Pazner S.
        • Kong X.P.
        • Jiang X.
        • et al.
        Cross-clade HIV-1 neutralizing antibodies induced with V3-scaffold protein immunogens following priming with gp120 DNA.
        J Virol. 2011; 85: 9887-9898
        • Smits H.H.
        • Gloudemans A.K.
        • van Nimwegen M.
        • et al.
        Cholera toxin B suppresses allergic inflammation through induction of secretory IgA.
        Mucosal Immunol. 2009; 2: 331-339
        • Stanford M.
        • Whittall T.
        • Bergmeier L.A.
        • et al.
        Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease.
        Clin Exp Immunol. 2004; 137: 201-208
        • Odumosu O.
        • Nicholas D.
        • Payne K.
        • et al.
        Cholera toxin B subunit linked to glutamic acid decarboxylase suppresses dendritic cell maturation and function.
        Vaccine. 2011; 29: 8451-8458
        • Sun J.B.
        • Czerkinsky C.
        • Holmgren J.
        Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit.
        Scan J Immunol. 2010; 71: 1-11
        • Ji J.
        • Shu X.
        • Li X.
        • et al.
        Cancer risk in hospitalized sarcoidosis patients: a follow-up study in Sweden.
        Ann Oncol. 2009; 20: 1121-1126
        • Ji J.
        • Shu X.
        • Li X.
        • et al.
        Cancer risk in hospitalised asthma patients.
        Br J Cancer. 2009; 100: 829-833
        • Shu X.
        • Ji J.
        • Li X.
        • et al.
        Cancer risk among patients hospitalized for Type 1 diabetes mellitus: a population-based cohort study in Sweden.
        Diabet Med. 2010; 27: 791-797
        • Hemminki K.
        • Liu X.
        • Ji J.
        • et al.
        Effect of autoimmune diseases on mortality and survival in subsequent digestive tract cancers.
        Ann Oncol. 2012; 23: 2179-2184
        • Lu W.
        • Qiu L.
        • Yan Z.
        • et al.
        Cytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit.
        Oncotarget. 2015; 6: 34537-34548