Abstract
BACKGROUND—Although some experimental studies have indicated that cholecystectomy may increase the risk of pancreatic cancer, data from epidemiological studies are conflicting. AIMS—We conducted a register based retrospective cohort study to explore the relationship between cholecystectomy and pancreatic cancer. SUBJECTS—The cohort included 87 263 men and 181 049 women with a documented cholecystectomy for cholelithiasis between 1965 and 1997. METHODS—By record linkage to the nationwide and virtually complete registers of Cancer, Emigration, and Causes of Death, the cohort was followed up until the occurrence of any cancer, emigration, death, or the end of follow up, 31 December 1997, whichever came first. Relative risk was estimated by standardised incidence ratio (SIR) using the Swedish nationwide sex, age, and calendar year specific cancer incidence rates as reference. RESULTS—During the period of observation, 1053 cases of pancreatic cancer were found, among which 231 (22%) occurred within 12 months after operation. After excluding cases and person years accrued during the first two years of follow up, we observed a non-significant 6% excess risk for pancreatic cancer (95% confidence interval (CI) −2 to 14%). The relative risk did not increase with increasing follow up duration, with a SIR equal to 0.98 (95% CI 0.79-1.20) 20 years or more after operation. Patients with a comorbidity of diabetes or chronic pancreatitis had higher relative risks (SIR=1.79, 95% CI 1.39-2.28; SIR=3.17, 95% CI 1.37-6.24, respectively). After excluding patients with recorded diabetes or chronic pancreatitis, the relative risk was close to unity (SIR=1.01, 95% CI 0.94-1.09). CONCLUSIONS—Our findings do not support the hypothesis that cholecystectomy increases the subsequent risk of pancreatic cancer. Keywords: pancreatic cancer; cholecystectomy; cohort study
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- Axelson J., Ihse I., Håkanson R. Pancreatic cancer: the role of cholecystokinin? Scand J Gastroenterol. 1992 Dec;27(12):993–998. doi: 10.3109/00365529209028128. [DOI] [PubMed] [Google Scholar]
- Borch K., Jönsson K. A., Zdolsek J. M., Halldestam I., Kullman E. Prevalence of gallstone disease in a Swedish population sample. Relations to occupation, childbirth, health status, life style, medications, and blood lipids. Scand J Gastroenterol. 1998 Nov;33(11):1219–1225. doi: 10.1080/00365529850172601. [DOI] [PubMed] [Google Scholar]
- Bueno de Mesquita H. B., Maisonneuve P., Moerman C. J., Walker A. M. Aspects of medical history and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands. Int J Cancer. 1992 Aug 19;52(1):17–23. doi: 10.1002/ijc.2910520105. [DOI] [PubMed] [Google Scholar]
- Carter D. C. Cancer of the pancreas. Gut. 1990 May;31(5):494–496. doi: 10.1136/gut.31.5.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chester J. F., Norris M. A., Lever J. V., Turnbull A. R., Britton D. C. Experimental pancreatic cancer in the Syrian hamster: effect of cholecystectomy. Digestion. 1989;44(1):36–40. doi: 10.1159/000199890. [DOI] [PubMed] [Google Scholar]
- Chow W. H., Johansen C., Gridley G., Mellemkjaer L., Olsen J. H., Fraumeni J. F., Jr Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas. Br J Cancer. 1999 Feb;79(3-4):640–644. doi: 10.1038/sj.bjc.6690101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cuzick J., Babiker A. G. Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease. Int J Cancer. 1989 Mar 15;43(3):415–421. doi: 10.1002/ijc.2910430312. [DOI] [PubMed] [Google Scholar]
- Diehl A. K. Epidemiology and natural history of gallstone disease. Gastroenterol Clin North Am. 1991 Mar;20(1):1–19. [PubMed] [Google Scholar]
- Ekbom A., Yuen J., Karlsson B. M., McLaughlin J. K., Adami H. O. Risk of pancreatic and periampullar cancer following cholecystectomy: a population-based cohort study. Dig Dis Sci. 1996 Feb;41(2):387–391. doi: 10.1007/BF02093833. [DOI] [PubMed] [Google Scholar]
- Everhart J., Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 1995 May 24;273(20):1605–1609. [PubMed] [Google Scholar]
- Farrow D. C., Davis S. Risk of pancreatic cancer in relation to medical history and the use of tobacco, alcohol and coffee. Int J Cancer. 1990 May 15;45(5):816–820. doi: 10.1002/ijc.2910450504. [DOI] [PubMed] [Google Scholar]
- Friedman G. D. Cholecystectomy not confirmed as a risk factor for pancreatic cancer. Int J Cancer. 1995 May 29;61(5):745–746. doi: 10.1002/ijc.2910610526. [DOI] [PubMed] [Google Scholar]
- Gullo L., Pezzilli R., Morselli-Labate A. M., Italian Pancreatic Cancer Study Group Risk of pancreatic cancer associated with cholelithiasis, cholecystectomy, or gastrectomy. Dig Dis Sci. 1996 Jun;41(6):1065–1068. doi: 10.1007/BF02088220. [DOI] [PubMed] [Google Scholar]
- Haddock G., Carter D. C. Aetiology of pancreatic cancer. Br J Surg. 1990 Oct;77(10):1159–1166. doi: 10.1002/bjs.1800771025. [DOI] [PubMed] [Google Scholar]
- Howatson A. G., Carter D. C. Pancreatic carcinogenesis-enhancement by cholecystokinin in the hamster-nitrosamine model. Br J Cancer. 1985 Jan;51(1):107–114. doi: 10.1038/bjc.1985.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hyvärinen H., Partanen S. Association of cholecystectomy with abdominal cancers. Hepatogastroenterology. 1987 Dec;34(6):280–284. [PubMed] [Google Scholar]
- Jain M., Howe G. R., St Louis P., Miller A. B. Coffee and alcohol as determinants of risk of pancreas cancer: a case-control study from Toronto. Int J Cancer. 1991 Feb 1;47(3):384–389. doi: 10.1002/ijc.2910470313. [DOI] [PubMed] [Google Scholar]
- Johnson F. E., LaRegina M. C., Martin S. A., Bashiti H. M. Cholecystokinin inhibits pancreatic and hepatic carcinogenesis. Cancer Detect Prev. 1983;6(3):389–402. [PubMed] [Google Scholar]
- Karlson B. M., Ekbom A., Josefsson S., McLaughlin J. K., Fraumeni J. F., Jr, Nyrén O. The risk of pancreatic cancer following pancreatitis: an association due to confounding? Gastroenterology. 1997 Aug;113(2):587–592. doi: 10.1053/gast.1997.v113.pm9247480. [DOI] [PubMed] [Google Scholar]
- Kuper H., Ye W., Weiderpass E., Ekbom A., Trichopoulos D., Nyrén O., Adami H. O. Alcohol and breast cancer risk: the alcoholism paradox. Br J Cancer. 2000 Oct;83(7):949–951. doi: 10.1054/bjoc.2000.1360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowenfels A. B., Maisonneuve P., Cavallini G., Ammann R. W., Lankisch P. G., Andersen J. R., Dimagno E. P., Andrén-Sandberg A., Domellöf L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993 May 20;328(20):1433–1437. doi: 10.1056/NEJM199305203282001. [DOI] [PubMed] [Google Scholar]
- Mack T. M., Yu M. C., Hanisch R., Henderson B. E. Pancreas cancer and smoking, beverage consumption, and past medical history. J Natl Cancer Inst. 1986 Jan;76(1):49–60. [PubMed] [Google Scholar]
- Nyrén O., McLaughlin J. K., Gridley G., Ekbom A., Johnell O., Fraumeni J. F., Jr, Adami H. O. Cancer risk after hip replacement with metal implants: a population-based cohort study in Sweden. J Natl Cancer Inst. 1995 Jan 4;87(1):28–33. doi: 10.1093/jnci/87.1.28. [DOI] [PubMed] [Google Scholar]
- Rosenberg L., Duguid W. P., Brown R. A. Cholecystectomy stimulates hypertrophy and hyperplasia in the hamster pancreas. J Surg Res. 1984 Aug;37(2):108–111. doi: 10.1016/0022-4804(84)90169-0. [DOI] [PubMed] [Google Scholar]
- Shibata A., Mack T. M., Paganini-Hill A., Ross R. K., Henderson B. E. A prospective study of pancreatic cancer in the elderly. Int J Cancer. 1994 Jul 1;58(1):46–49. doi: 10.1002/ijc.2910580109. [DOI] [PubMed] [Google Scholar]
- Silverman D. T., Schiffman M., Everhart J., Goldstein A., Lillemoe K. D., Swanson G. M., Schwartz A. G., Brown L. M., Greenberg R. S., Schoenberg J. B. Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer. 1999 Aug;80(11):1830–1837. doi: 10.1038/sj.bjc.6690607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. P., Solomon T. E., Bagheri S., Kramer S. Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990. Dig Dis Sci. 1990 Nov;35(11):1377–1384. doi: 10.1007/BF01536744. [DOI] [PubMed] [Google Scholar]
- Ura H., Makino T., Ito S., Tsutsumi M., Kinugasa T., Kamano T., Ichimiya H., Konishi Y. Combined effects of cholecystectomy and lithocholic acid on pancreatic carcinogenesis of N-nitrosobis(2-hydroxypropyl)amine in Syrian golden hamsters. Cancer Res. 1986 Sep;46(9):4782–4786. [PubMed] [Google Scholar]
- Watanapa P., Williamson R. C. Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation. Br J Cancer. 1993 May;67(5):877–884. doi: 10.1038/bjc.1993.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wynder E. L., Mabuchi K., Maruchi N., Fortner J. G. A case control study of cancer of the pancreas. Cancer. 1973 Mar;31(3):641–648. doi: 10.1002/1097-0142(197303)31:3<641::aid-cncr2820310323>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]