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Does diabetes mellitus with or without gallstones increase the risk of gallbladder cancer? Results from a population-based cohort study

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Previous studies have suggested that diabetes mellitus (DM) is a risk factor for gallbladder cancer; however, it remains unclear whether DM with or without gallstones increases the risk of gallbladder cancer. The aim of this study was to evaluate the risk factors for gallbladder cancer, including sex, hypertension, hyperlipidemia, gallstones, and DM.

Methods

The study cohort consisted of 214,179 subjects newly diagnosed with diabetes (cases) collected from the claims data of the Health Insurance Program of Taiwan from 2000 to 2001 who were retrospectively enrolled. The control group consisted of 206,860 subjects without diabetes, matched with the cases for sex, age, and index year. The subjects were followed up until the end of 2008. The effects of the risk factors on the incidence of gallbladder cancer were evaluated with Cox’s proportional hazard regression models.

Results

The risk of gallbladder cancer was higher in the DM group than in the non-DM group, with a hazard ratio (HR) of 1.53 [95 % confidence interval (CI) 1.22–1.90]. Gallstones were also a risk factor for gallbladder cancer, with an HR of 2.52 (95 % CI 1.11–5.73). DM and gallstones were synergistic risk factors for gallbladder cancer (p < 0.0001), with an HR of 5.37 (95 % CI 3.17–9.10) for subjects with both diseases in relation to those with neither of these conditions.

Conclusions

In the present long-term cohort study, DM with or without gallstones increased the risk of gallbladder cancer. Gallstones were independently related to gallbladder cancer, and DM and gallstones were synergistic risk factors for gallbladder cancer.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.

    Article  PubMed  Google Scholar 

  2. NHRI Communications [e-news]. Available from http://enews.nhri.org.tw/enews_list_new2_more.php?volume_indx=307&showx=showarticle&article_indx=7194 (2009). Accessed 8 August 2010.

  3. Reid KM, Ramos-De la Medina A, Donohue JH. Diagnosis and surgical management of gallbladder cancer: a review. J Gastrointest Surg. 2007;11:671–81.

    Article  PubMed  Google Scholar 

  4. Matsusaka S, Yamasaki H, Kitayama Y, Okada T, Maeda S. Occult gallbladder carcinoma diagnosed by a laparoscopic cholecystectomy. Surg Today. 2003;33:740–2.

    Article  PubMed  Google Scholar 

  5. Piehler JM, Crichlow RW. Primary carcinoma of the gallbladder. Surg Gynecol Obstet. 1978;147:929–42.

    PubMed  CAS  Google Scholar 

  6. Chijiiwa K, Tanaka M. Carcinoma of the gallbladder: an appraisal of surgical resection. Surgery. 1994;115:751–6.

    PubMed  CAS  Google Scholar 

  7. Bartlett DL, Fong Y, Fortner JG, Brennan MF, Blumgart LH. Long-term results after resection for gallbladder cancer. Implications for staging and management. Ann Surg. 1996;224:639–46.

    Article  PubMed  CAS  Google Scholar 

  8. Wullstein C, Woeste G, Barkhausen S, Gross E, Hopt UT. Do complications related to laparoscopic cholecystectomy influence the prognosis of gallbladder cancer? Surg Endosc. 2002;16:828–32.

    Article  PubMed  CAS  Google Scholar 

  9. Lazcano-Ponce EC, Miquel JF, Muñoz N, Herrero R, Ferrecio C, Wistuba II, et al. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51:349–64.

    Article  PubMed  CAS  Google Scholar 

  10. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118:1591–602.

    Article  PubMed  CAS  Google Scholar 

  11. Kiran RP, Pokala N, Dudrick SJ. Incidence pattern and survival for gallbladder cancer over three decades—an analysis of 10301 patients. Ann Surg Oncol. 2007;14:827–32.

    Article  PubMed  CAS  Google Scholar 

  12. Zatonski WA, Lowenfels AB, Boyle P, Maisonneuve P, Bueno de Mesquita HB, et al. Epidemiologic aspects of gallbladder cancer: a case–control study of the SEARCH Program of the International Agency for Research on Cancer. J Natl Cancer Inst. 1997;89:1132–8.

    Article  PubMed  CAS  Google Scholar 

  13. Strom BL, Soloway RD, Rios-Dalenz JL, Rodriguez-Martinez HA, West SL, Kinman JL, et al. Risk factors for gallbladder cancer. An international collaborative case–control study. Cancer. 1995;76:1747–56.

    Article  PubMed  CAS  Google Scholar 

  14. Park KW, Kim SH, Choi SH, Lee WJ. Differentiation of nonneoplastic and neoplastic gallbladder polyps 1 cm or bigger with multi-detector row computed tomography. J Comput Assist Tomogr. 2010;34:135–9.

    Article  PubMed  Google Scholar 

  15. Chijiiwa K, Kimura H, Tanaka M. Malignant potential of the gallbladder in patients with anomalous pancreaticobiliary ductal junction. The difference in risk between patients with and without choledochal cyst. Int Surg. 1995;80:61–4.

    PubMed  CAS  Google Scholar 

  16. Shukla VK, Chauhan VS, Mishra RN, Basu S. Lifestyle, reproductive factors and risk of gallbladder cancer. Singap Med J. 2008;49:912–5.

    CAS  Google Scholar 

  17. Jamal MM, Yoon EJ, Vega KJ, Hashemzadeh M, Chang KJ. Diabetes mellitus as a risk factor for gastrointestinal cancer among American veterans. World J Gastroenterol. 2009;15:5274–8.

    Article  PubMed  Google Scholar 

  18. Ren HR, Yu T, Liu C, Li YQ. Diabetes mellitus and increased risk of biliary tract cancer: systemic review and meta-analysis. Cancer Causes Control. 2011;22:837–47.

    Article  PubMed  Google Scholar 

  19. Tai TY, Yang CL, Chang CJ, Chang SM, Chen YH, Lin BJ, et al. Epidemiology of diabetes mellitus among adults in Taiwan, R.O.C. J Med Assoc Thai. 1987;70(Suppl 2):42–8.

    PubMed  Google Scholar 

  20. Lin JD, Shieh WB, Huang MJ, Huang HS. Diabetes mellitus and hypertension based on the family history and 2-h postprandial blood sugar in the Ann-Lo district (northern Taiwan). Diabetes Res Clin Pract. 1993;20:75–85.

    Article  PubMed  CAS  Google Scholar 

  21. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–7.

    Article  PubMed  CAS  Google Scholar 

  22. Lu JFR, Hsiaa WC. Does Universal health insurance make health care unaffordable? Lessons from Taiwan. Health Aff. 2003;22:77–88.

    Article  Google Scholar 

  23. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21:1414–31.

    Article  PubMed  CAS  Google Scholar 

  24. Hassan MM, Hwang LY, Hatten CJ, Swaim M, Li D, Abbruzzese JL, et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002;36:1206–13.

    Article  PubMed  CAS  Google Scholar 

  25. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA. 2005;293:194–202.

    Article  PubMed  CAS  Google Scholar 

  26. Larsson SC, Giovannucci E, Wolk A. Diabetes and colorectal cancer incidence in the cohort of Swedish men. Diabetes Care. 2005;28:1805–7.

    Article  PubMed  Google Scholar 

  27. Nicolucci A. Epidemiological aspects of neoplasms in diabetes. Acta Diabetol. 2010;47:87–95.

    Article  PubMed  Google Scholar 

  28. Hsing AW, Gao YT, Han TQ, Rashid A, Sakoda LC, Wang BS, et al. Gallstones and the risk of biliary tract cancer; a population-based study in China. Br J Cancer. 2007;97:1577–82.

    Article  PubMed  CAS  Google Scholar 

  29. Adami HO, Chow WH, Nyren O, Berne C, Linet MS, Ekbom A, et al. Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst. 1996;88:1472–7.

    Article  PubMed  CAS  Google Scholar 

  30. Shebl FM, Andreotti G, Rashid A, Gao YT, Yu K, Shen MC, et al. Diabetes in relation to biliary tract cancer and stones; a population-based study in Shanghai, China. Br J Cancer. 2010;103:115–9.

    Article  PubMed  CAS  Google Scholar 

  31. Grainge MJ, Weit J, Solaymani-Dodaran M, Aithal GP, Card TR. The antecedents of biliary cancer: a primary care case-control study in the United Kingdom. Br J Cancer. 2009;100:178–80.

    Article  PubMed  CAS  Google Scholar 

  32. Kuriki K, Hirose K, Tajima K. Diabetes and cancer risk for all and specific sites among Japanese men and women. Eur J Cancer Prev. 2007;16:83–9.

    Article  PubMed  Google Scholar 

  33. Taner CB, Nagorney DM, Donohue JH. Surgical treatment of gallbladder cancer. J Gastrointest Surg. 2004;8:83–9.

    Article  PubMed  Google Scholar 

  34. Memon MA, Anwar S, Shiwani MH, Memon B. Gallbladder carcinoma: a retrospective analysis of twenty-two years experience of a single teaching hospital. Int Semin Surg Oncol. 2005;2:6.

    Article  PubMed  Google Scholar 

  35. Andreotti G, Liu E, Gao YT, Safaeian M, Rashid A, Shen MC, et al. Medical history and the risk of biliary tract cancers in Shanghai, China. Cancer Causes Control. 2011;22:1289–96.

    Article  PubMed  Google Scholar 

  36. Hsing AW, Bai Y, Androtti G, Rashid A, Deng J, Chen J, et al. Family history of gallstones and the risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China. Int J Cancer. 2007;121:832–8.

    Article  PubMed  CAS  Google Scholar 

  37. Ruhl CE, Everhart JE. Gallstone disease is associated with increased mortality in the United States. Gastroenterology. 2011;140:508–16.

    Article  PubMed  Google Scholar 

  38. Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR. The metabolic syndrome and risk of incident colorectal cancer. Cancer. 2006;107:28–36.

    Article  PubMed  Google Scholar 

  39. Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med. 1999;130:883–90.

    Article  PubMed  CAS  Google Scholar 

  40. Veugelers PJ, Porter GA, Guernsey DL, Casson AG. Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma. Dis Esophagus. 2006;19:321–8.

    Article  PubMed  CAS  Google Scholar 

  41. Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001;91:421–30.

    Article  PubMed  CAS  Google Scholar 

  42. Hsing AW, Sakoda LC, Rashid A, Chen J, Shen MC, Han TQ, et al. Body size and the risk of biliary tract cancer: a population-based study in China. Br J Cancer. 2008;99:811–5.

    Article  PubMed  CAS  Google Scholar 

  43. Shebl FM, Andreotti G, Meyer TE, Gao YT, Rashid A, Yu K, et al. Metabolic syndrome and insulin resistance in relation to biliary tract cancer and stone risks: a population-based study in Shanghai, China. Br J Cancer. 2011;105:1424–9.

    Article  PubMed  CAS  Google Scholar 

  44. Khandwaa HM, McCucheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000;21:215–44.

    Article  Google Scholar 

  45. Grau MV, Rees JR, Baron JA. Chemoprevention in gastrointestinal cancers: current status. Basic Clin Pharmacol Toxicol. 2006;98:281–7.

    Article  PubMed  CAS  Google Scholar 

  46. Diehl AK. Gallstone size and the risk of gallbladder cancer. JAMA. 1983;250:2323–6.

    Article  PubMed  CAS  Google Scholar 

  47. Lowenfels AB, Walker AM, Althaus DP, Townsend G, Domellof L. Gallstone growth, size, and risk of gallbladder cancer: an interracial study. Int J Epidemiol. 1989;18:50–4.

    Article  PubMed  CAS  Google Scholar 

  48. Roa I, Ibacache G, Roa J, Araya J, de Aretxabala X, Munoz S. Gallstones and gallbladder cancer–volume and weight of gallstones are associated with gallbladder cancer: a case–control study. J Surg Oncol. 2006;93:624–8.

    Article  PubMed  Google Scholar 

  49. Csendes A, Becerra M, Rojas J, Medina E. Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: a prospective study of 592 cases. J Gastrointest Surg. 2000;4:481–5.

    Article  PubMed  CAS  Google Scholar 

  50. Lin CC, Lai MS, Syu CY, Chang SC, Tseng FY. Accuracy of diabetes diagnosis in health insurance claims data in Taiwan. J Formos Med Assoc. 2005;104:157–63.

    PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Sciences Council, Executive Yuan (grant numbers NSC 95-2625-Z-039-002, NSC 96-2625-Z-039-003, NSC 97-2625-M-039-003, NSC 98-2621-M-039-001), China Medical University Hospital (grant number 1MS1), and the Taiwan Department of Health Clinical Trial and Research Center for Excellence (grant number DOH99-TD-B-111-004). This study is based on data from the National Health Insurance Research Database, which is provided by the Bureau of National Health Insurance, Department of Health, Taiwan, and managed by the National Health Research Institutes. The interpretations and conclusions contained herein do not represent the opinions of the Bureau of National Health Insurance, Department of Health, or the National Health Research Institutes.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. School of Chinese Medicine, China Medical University, Taichung, Taiwan

    Hsueh-Chou Lai & Ching-Chou Chen

  2. Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    Hsueh-Chou Lai, Jen-Wei Chou & Cheng-Yuan Peng

  3. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan

    Shih-Ni Chang, Che-Chen Lin & Fung-Chang Sung

  4. Division of Endocrinology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    Ching-Chou Chen

  5. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan

    Shih-Wei Lai

  6. Department of Public Health, China Medical University, Taichung, Taiwan

    Fung-Chang Sung

  7. Graduate Institute of Biostatistics, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan

    Yu-Fen Li

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  1. Hsueh-Chou Lai
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Correspondence to Yu-Fen Li.

Additional information

H.-C. Lai and S.-N. Chang contributed equally to this work.

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Lai, HC., Chang, SN., Lin, CC. et al. Does diabetes mellitus with or without gallstones increase the risk of gallbladder cancer? Results from a population-based cohort study. J Gastroenterol 48, 856–865 (2013). https://doi.org/10.1007/s00535-012-0683-z

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  • DOI: https://doi.org/10.1007/s00535-012-0683-z

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