Skip to main content
Springer Nature Link
Log in

Salmonella typhi and Gallbladder Cancer

  • Chapter
  • First Online:
Bacteria and Cancer

Abstract

This chapter reviews the current epidemiological indicators suggesting that Salmonella typhi could be a causal agent of gallbladder cancer (GBC). Both GBC and S. typhi occur in poor areas and are frequent in some Latin American (Chile, Mexico) and Asian (India, Korea) countries. In the developed world, typhoid or GBC are seen mainly among travelers or immigrants. While most people are susceptible to S. typhi infection, only 3% of infected become chronic carriers of S. typhi in their biliary tract. Gallstone carriers have a 6–15 times higher risk of becoming S. typhi carriers (Hofmann and Chianale, J Infect Dis, 167(4):993–994, 1993). S. typhi chronic carriers have 3–200 times higher risk of GBC than non-carriers, and 1–6% lifetime risk to develop GBC (Caygill et al., Lancet 343(8889):83–84, 1994; Eur J Cancer Prev 4(2):187–193, 1995). S. typhi associated relative risk of GBC is higher than that for gallstones (GS) alone; GS carriers have OR from 3 to 6 and less than 1% lifetime risk to develop GBC (Hsing et al., Biliary tract cancer. In: Schottenfeld D, Fraumeni JF (eds) Cancer epidemiology and prevention, 3rd edn. Oxford University Press, New York, pp. 787–800, 2006; Pandey, J Surg Oncol 93(8):640–643, 2006; Diehl, JAMA 250(17):2323–2326, 1983). The major steps in gallbladder carcinogenesis would be: S. typhi acute infection, S. typhi persistence as a chronic infection for decades, latency of 10 years to progress from metaplasia or dysplasia to pre cancer, and 5 years latency for invasion. Mechanistic research is needed to understand S. typhi-GBC association and provide tools for its control. Nevertheless, with the current epidemiological evidence much suffering could be prevented by: (i) health education, basic sanitation and food hygiene, to interrupt S. typhi transmission; (ii) treatment of chronic carriers, (iii) promotion of healthy diet and lifestyles to prevent gallstone formation, and (iv) cholecystectomy of gallstone disease in high risk areas to prevent invasive GBC.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CDT:

Cytolethal distending toxin

GB:

Gallbladder

GBC:

Gallbladder cancer

GS:

Gallstone

GSD:

Gallstone disease

HR:

Hazard ratio

OR:

Odds ratio

SMR:

Standard mortality ratio

TF:

Typhoid fever

References

  • Albores-Saavedra J, Alcántra-Vazquez A, Cruz-Ortiz H et al (1980) The precursor lesions of invasive gallbladder carcinoma. Hyperplasia, atypical hyperplasia and carcinoma in situ. Cancer 45(5):919–927

    Article  PubMed  CAS  Google Scholar 

  • Ames WR, Robins M (1943) Age and sex as factors in the development of the typhoid carrier state, and a method for estimating carrier prevalence. Am J Public Health Nations Health 33(3):221–230

    Article  PubMed  CAS  Google Scholar 

  • Andia ME, Hsing AW, Andreotti G et al (2008) Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study. Int J Cancer 123(6):1411–1416

    Article  PubMed  CAS  Google Scholar 

  • Andreotti G, Chen J, Gao YT et al (2008) Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev 17(3):525–534

    Article  PubMed  CAS  Google Scholar 

  • Baker S, Hanage WP, Holt KE (2010) Navigating the future of bacterial molecular epidemiology. Curr Opin Microbiol 13(5):640–645

    Article  PubMed  CAS  Google Scholar 

  • Batra Y, Pal S, Dutta U et al (2005) Gallbladder cancer in India: a dismal picture. J Gastroenterol Hepatol 20(2):309–314

    Article  PubMed  Google Scholar 

  • Bertran E, Heise K, Andia ME et al (2010) Gallbladder cancer: incidence and survival in a high-risk area of Chile. Int J Cancer 127(10):2446–2454

    Article  PubMed  CAS  Google Scholar 

  • Brett M, Barker DJ (1976) The world distribution of gallstones. Int J Epidemiol 5(4):335–341

    Article  PubMed  CAS  Google Scholar 

  • Caygill CPJ, Hill MJ (2000) Salmonella typhi/paratyphi and gallbladder cancer. In: Goedart JJ (ed) Infectious causes of cancer: targets for intervention. Humana Press, Totowa

    Google Scholar 

  • Caygill CPJ, Hill MJ, Braddick M et al (1994) Cancer mortality in chronic typhoid and paratyphoid carriers. Lancet 343(8889):83–84

    Article  PubMed  CAS  Google Scholar 

  • Caygill CPJ, Braddick M, Knowles RL et al (1995) The association between typhoid carriage, typhoid infection and subsequent cancer at a number of sites. Eur J Cancer Prev 4(2):187–193

    Article  PubMed  CAS  Google Scholar 

  • Chang SC, Rashid A, Gao YT et al (2008) Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone: a population-based case-control study in Shanghai, China. Carcinogenesis 29(5):944–948

    Article  PubMed  CAS  Google Scholar 

  • Chianale J, del Pino G, Nervi F (1990) Increasing gall-bladder cancer mortality rate during the last decade in Chile, a high-risk area. Int J Cancer 46(6):1131–1133

    Article  PubMed  CAS  Google Scholar 

  • Crump JA, Mintz ED (2010) Global trends in typhoid and paratyphoid fever. Clin Infect Dis 50(2):241–246

    Article  PubMed  Google Scholar 

  • Crump JA, Luby SP, Mintz ED (2004) The global burden of typhoid fever. Bull World Health Organ 82(5):346–353

    PubMed  Google Scholar 

  • Crump JA, Ram PK, Gupta SK et al (2008) Part I. Analysis of data gaps pertaining to Salmonella enterica serotype Typhi infections in low and medium human development index countries, 1984–2005. Epidemiol Infect 136(4):436–448

    Article  PubMed  CAS  Google Scholar 

  • Csendes A, Becerra M, Smok G et al (1991) Prevalence of gallbladder neoplasms in cholecystectomies. Rev Med Chil 119(8):887–890

    PubMed  CAS  Google Scholar 

  • Csendes A, Becerra M, Rojas J et al (2000) Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: a prospective study of 592 cases. J Gastrointest Surg 4(5):481–485

    Article  PubMed  CAS  Google Scholar 

  • Curado MP, Edwards B, Shin HR et al (eds) (2007) Cancer incidence in five continents, vol IX. IARC scientific publication no. 160. Available from http://www.iarc.fr/en/Publications/PDFs-online/Cancer-Epidemiology/IARC-Scientific-Publication-No.-155

  • Cvjetanovic B, Grab B, Uemura K (1971) Epidemiological model of typhoid fever and its use in the planning and evaluation of antityphoid immunization and sanitation programmes. Bull World Health Organ 45(1):53–75

    PubMed  CAS  Google Scholar 

  • Diehl AK (1983) Gallstone size and the risk of gallbladder cancer. JAMA 250(17):2323–2326

    Article  PubMed  CAS  Google Scholar 

  • Diehl AK (1998) Gallstone disease in Mestizo Hispanics. Gastroenterology 115(4):1012–1015

    Article  PubMed  CAS  Google Scholar 

  • Diehl AK, Stern MP, Ostrower VS et al (1980) Prevalence of clinical gallbladder disease in Mexican-American, Anglo, and black women. South Med J 73(4):438–441

    Article  PubMed  CAS  Google Scholar 

  • el-Zayadi A, Ghoneim M, Kabil SM et al (1991) Bile duct carcinoma in Egypt: possible etiological factors. Hepatogastroenterology 38(4):337–340

    PubMed  CAS  Google Scholar 

  • Ferlay J, Bray F, Pisani P et al (2004) GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide IARC Cancer Base No. 5 version 2.0. IARC Press, Lyon

    Google Scholar 

  • Ferreccio C, Levine MM, Manterola A et al (1984) Benign bacteremia caused by Salmonella typhi and paratyphi in children aged younger than 2 years. J Pediatr 104(6):899–901

    Article  PubMed  CAS  Google Scholar 

  • Friedrich N, Völzke H, Hampe J et al (2009) Known risk factors do not explain disparities in gallstone prevalence between Denmark and northeast Germany. Am J Gastroenterol 104(1):89–95

    Article  PubMed  Google Scholar 

  • Gabrielli M, Hugo S, Dominquez A et al (2010) Mortality due to gallbladder cancer: retrospective analysis in three Chilean hospitals. Rev Med Chil 138(11):1357–1364

    PubMed  Google Scholar 

  • Galman C, Miquel JF, Pérez RM et al (2004) Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians. Gastroenterology 126(3):741–748

    Article  PubMed  Google Scholar 

  • Goldin RD, Roa JC (2009) Gallbladder cancer: a morphological and molecular update. Histopathology 55(2):218–229

    Article  PubMed  Google Scholar 

  • Gomez-Roel X, Arrieta O, Leon-Rodriguez E (2007) Prognostic factors in gallbladder and biliary tract cancer. Med Oncol 24(1):77–83

    Article  PubMed  Google Scholar 

  • Grimaldi CH, Nelson RG, Pettitt DJ et al (1993) Increased mortality with gallstone disease: results of a 20-year population-based survey in Pima Indians. Ann Intern Med 118(3):185–190

    PubMed  CAS  Google Scholar 

  • Hemminki K, Mousavi SM, Barndt A et al (2010) Liver and gallbladder cancer in immigrants to Sweden. Eur J Cancer 46(5):926–931

    Article  PubMed  Google Scholar 

  • Hofmann E, Chianale J (1993) Blood group antigen secretion and gallstone disease in the Salmonella typhi chronic carrier state. J Infect Dis 167(4):993–994

    Article  PubMed  CAS  Google Scholar 

  • Hsing AW, Rashid A, Devesa SS et al (2006) Biliary tract cancer. In: Schottenfeld D, Fraumeni JF (eds) Cancer epidemiology and prevention, 3rd edn. Oxford University Press, New York, pp 787–800

    Chapter  Google Scholar 

  • International Agency for Research on Cancer (IARC) (2009) Cancer Mondial. http://www-dep.iarc.fr/. Accessed 31 Dec 2009.

  • Karayalçin R, Genç V, Karaca AS et al (2010) Prevalence of cholelithiasis in a Turkish population sample of postmenopausal women. Turk J Gastroenterol 21(4):416–420

    PubMed  Google Scholar 

  • Kayahara M, Nagakawa T, Nakagawara H et al (2008) Prognostic factors for gallbladder cancer in Japan. Ann Surg 248(5):807–814

    Article  PubMed  Google Scholar 

  • Khan AA, Shrivastava A (2010) Bacterial infections associated with cancer: possible implication in etiology with special reference to lateral gene transfer. Cancer Metastasis Rev 29(2):331–337

    Article  PubMed  Google Scholar 

  • Khan HN, Harrison M, Bassett EE et al (2009) A 10-year follow-up of a longitudinal study of gallstone prevalence at necropsy in South East England. Dig Dis Sci 54(12):2736–2741

    Article  PubMed  Google Scholar 

  • Konstantinidis IT, Deshpande V, Genevay M et al (2009) Trends in presentation and survival for gallbladder cancer during a period of more than 4 decades: a single-institution experience. Arch Surg 144(5):441–447

    Article  PubMed  Google Scholar 

  • Kothari A, Pruthi A, Chugh TD (2008) The burden of enteric fever. J Infect Dev Ctries 2(4):253–259

    PubMed  Google Scholar 

  • Lai CW, Chan RC, Cheng AF et al (1992) Common bile duct stones: a cause of chronic salmonellosis. Am J Gastroenterol 87(9):1198–1199

    PubMed  CAS  Google Scholar 

  • Lanata CF, Ristori C, Jimenez L et al (1983) Vi serology in detection of chronic Salmonella typhi carriers in an endemic area. Lancet 322(8347):441–443

    Article  Google Scholar 

  • Laval E, Ferreccio C (2007) Fiebre Tifoidea: emergencia, cuspide y desaparicion de una enfermedad infecciosa en Chile. Rev Chil Infect 24:435–440

    Google Scholar 

  • Lazcano-Ponce EC, Miquel JF, Munoz N et al (2001) Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin 51(6):349–364

    Article  PubMed  CAS  Google Scholar 

  • Lemrow SM, Perdue DG, Stewart SL et al (2008) Gallbladder cancer incidence among American Indians and Alaska Natives, US, 1999-2004. Cancer 113:1266–1273

    Article  PubMed  Google Scholar 

  • Levine MM, Black RE, Lanata C (1982) Precise estimation of the numbers of chronic carriers of Salmonella typhi in Santiago, Chile, an endemic area. J Infect Dis 146(6):724–726

    Article  PubMed  CAS  Google Scholar 

  • Levine MM, Ristori C, Ferreccio C (1984) Reply. J Infect Dis 149(1):125–126

    Article  Google Scholar 

  • Lieber MM (1952) The incidence of gallstones and their correlation with other diseases. Ann Surg 135(3):394–405

    Article  PubMed  CAS  Google Scholar 

  • Lin FY, Becke JM, Groves C et al (1988) Restaurant-associated outbreak of typhoid fever in Maryland: identification of carrier facilitated by measurement of serum Vi antibodies. J Clin Microbiol 26(6):1194–1197

    PubMed  CAS  Google Scholar 

  • Losonsky GA, Ferreccio C, Kotloff KL et al (1987) Development and evaluation of an enzyme-linked immunosorbent assay for serum Vi antibodies for detection of chronic Salmonella typhi carriers. J Clin Microbiol 25(12):2266–2269

    PubMed  CAS  Google Scholar 

  • Lowenfels AB, Walker AM, Althaus DP et al (1989) Gallstone growth, size, and risk of gallbladder cancer: an interracial study. Int J Epidemiol 18(1):50–54

    Article  PubMed  CAS  Google Scholar 

  • Lynch MF, Blanton EM, Bulens S et al (2009) Typhoid fever in the United States, 1999-2006. JAMA 302(8):859–865

    Article  PubMed  CAS  Google Scholar 

  • Mellemgaard A, Gaarslev K (1988) Risk of hepatobiliary cancer in carriers of Salmonella typhi. J Natl Cancer Inst 80(4):288

    PubMed  CAS  Google Scholar 

  • Méndez-Sánchez N, King-Martínez AC, Ramos MH et al (2004) The Amerindian’s genes in the Mexican population are associated with development of gallstone disease. Am J Gastroenterol 99(11):2166–2170

    Article  PubMed  Google Scholar 

  • Nath G, Singh YK, Kumar K et al (2008) Association of carcinoma of the gallbladder with typhoid carriage in a typhoid endemic area using nested PCR. J Infect Dev Ctries 2(4):302–307

    Article  PubMed  CAS  Google Scholar 

  • Nath G, Gulati AK, Shukla VK (2010) Role of bacteria in carcinogenesis, with special reference to carcinoma of the gallbladder. World J Gastroenterol 16(43):5395–5404

    Article  PubMed  Google Scholar 

  • Nervi F, Raddatz A, Zamorano N (1984) Overestimation of the numbers of chronic carriers of Salmonella typhi in Santiago. J Infect Dis 149(1):124–126

    Article  PubMed  CAS  Google Scholar 

  • Pandey M (2006) Environmental pollutants in gallbladder carcinogenesis. J Surg Oncol 93(8):640–643

    Article  PubMed  CAS  Google Scholar 

  • Parry CM, Hien TT, Dougan G et al (2002) Typhoid fever. N Engl J Med 347(22):1770–1782

    Article  PubMed  CAS  Google Scholar 

  • Prouty AM, Schwesinger WH, Gunn JS (2002) Biofilm formation and interaction with the surfaces of gallstones by Salmonella spp. Infect Immun 70(5):2640–2649

    Article  PubMed  CAS  Google Scholar 

  • Ristori C, Rodríguez H, Vicent P et al (1982a) Investigation of the Salmonella typhi-paratyphi ­carrier state in cases of surgical intervention for gallbladder disease. Bull Pan Am Health Organ 16(2):161–171

    PubMed  CAS  Google Scholar 

  • Ristori C, Rodríguez H, Vicent P et al (1982b) Persistence of the Salmonella typhi-paratyphi carrier state after gallbladder removal. Bull Pan Am Health Organ 16(4):361–366

    PubMed  CAS  Google Scholar 

  • Roa I, Araya JC, Villaseca M (1996) Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression. Gastroenterology 111(1):232–236

    Article  PubMed  CAS  Google Scholar 

  • Roa I, de Aretxabala X, Araya JC et al (2006) Preneoplastic lesions in gallbladder cancer. J Surg Oncol 93(8):615–623

    Article  PubMed  Google Scholar 

  • Roa EI, Muñoz NS, Ibacache SG et al (2009) Natural history of gallbladder cancer. Analysis of biopsy specimens. Rev Med Chil 137(7):873–880

    PubMed  Google Scholar 

  • Ruhl CE, Everhart JE (2011) Gallstone disease is associated with increased mortality in the United States. Gastroenterology 140(2):508–516

    Article  PubMed  Google Scholar 

  • Sears SD, Ferreccio C, Levine MM et al (1984) The use of Moore swabs for isolation of Salmonella typhi from irrigation water in Santiago, Chile. J Infect Dis 149(4):640–642

    Article  PubMed  CAS  Google Scholar 

  • Sears SD, Ferreccio C, Levine MM (1986) Sensitivity of Moore sewer swabs for isolating Salmonella typhi. Appl Environ Microbiol 51(2):425–426

    PubMed  CAS  Google Scholar 

  • Serra I, Calvo A, Maturana M et al (1990) Changing trends of gall-bladder cancer in Chile, a high-risk area. Int J Cancer 45(2):376–377

    Article  PubMed  CAS  Google Scholar 

  • Serra I, Yamamoto M, Calvo A et al (2002) Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Int J Cancer 102(4):407–411

    Article  PubMed  CAS  Google Scholar 

  • Shukla VK, Singh H, Pandey M et al (2000) Carcinoma of the gallbladder–is it a sequel of typhoid? Dig Dis Sci 45(5):900–903

    Article  PubMed  CAS  Google Scholar 

  • Siddiqui FJ, Rabbani F, Hasan R et al (2006) Typhoid fever in children: some epidemiological considerations from Karachi, Pakistan. Int J Infect Dis 10(3):215–222

    Article  PubMed  Google Scholar 

  • Tewari M, Mishra RR, Shukla HS (2010) Salmonella typhi and gallbladder cancer: report from an endemic region. Hepatobiliary Pancreat Dis Int 9(5):524–530

    PubMed  CAS  Google Scholar 

  • Unisa S, Jagannath P, Dhir V et al (2011) Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India. HPB 13(2):117–125

    Article  PubMed  Google Scholar 

  • Vaishnavi C, Kochhar R, Singh G et al (2005) Epidemiology of typhoid carriers among blood donors and patients with biliary, gastrointestinal and other related diseases. Microbiol Immunol 49(2):107–112

    PubMed  CAS  Google Scholar 

  • Welton JC, Marr JS, Friedman SM (1979) Association between hepatobiliary cancer and typhoid carrier state. Lancet 313(8120):791–794

    Article  Google Scholar 

  • Wistuba II, Gazdar AF (2004) Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer 4(9):695–706

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Salud Pública/Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 434, Santiago, Chile

    Catterina Ferreccio

Authors
  1. Catterina Ferreccio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catterina Ferreccio .

Editor information

Editors and Affiliations

  1. Vinay Nagar 2C, Gwalior, 474012, Madhya Pradesh, India

    Abdul Arif Khan

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Ferreccio, C. (2012). Salmonella typhi and Gallbladder Cancer. In: Khan, A. (eds) Bacteria and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2585-0_5

Download citation

Publish with us

Policies and ethics