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Risk of Colorectal Cancer and Other Cancers in Patients with Gall Stones

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Risk of Colorectal Cancer and Other Cancers in Patients with Gall Stones Gut 1996; 39:439-443 439 Risk of colorectal cancer and other cancers in patients with gall stones Gut: first published as 10.1136/gut.39.3.439 on 1 September 1996. Downloaded from C Johansen, Wong-Ho Chow, T J0rgensen, L Mellemkjaer, G Engholm, J H Olsen Abstract Although the relation between cholecystec- Background-The occurrence of gall tomy and colorectal cancer has been con- stones has repeatedly been associated with sidered in many studies, the results are equi- an increased risk for cancer of the colon, vocal"; most of the case-control studies but risk associated with cholecystectomy showed a positive relation, but only the two remains unclear. largest cohort studies showed significantly Aims-To evaluate the hypothesis in a increased risks, which were restricted to nationwide cohort ofmore than 40 000 gall women and to the proximal part of the stone patients with complete follow up colon.'4 15 including information of cholecystectomy These results suggest that gall stones, and and obesity. possibly cholecystectomy, which are done Patients-In the population based study mainly as a result ofgall stones increase the risk described here, 42098 patients with gall for colon cancer, particularly among women stones in 1977-1989 were identified in the and in the proximal part of the colon. One Danish Hospital Discharge Register. hypothesis is that post-cholecystectomy Methods-These patients were linked to changes in the composition and secretion of the Danish Cancer Registry to assess their bile salts affect enterohepatic circulation and risks for colorectal and other cancers exposure of the colon to bile acids,'6 '` which during follow up to the end of 1992. may promote the development of colon Results-The analysis showed a modest cancer.'8 On the other hand, abnormal bile increase in the number of cancers at all acid and cholesterol metabolism that pre- sites combined (n=3940; RR, 1.07; 950/o disposes to gall stones also may increase the confidence intervals (CI), 1.0 to 1.1). A risk of colon cancer.'9 The relation may also be weak association was found for cancer of influenced by shared determinants of gall the colon (n=360; RR, 1.09; 950/o CI 1.0 to stones and colon cancer such as oestrogens and 1.2), which remained unchanged when obesity.20 21 analysed by sex, anatomical subsite, and This study has the advantage in that it http://gut.bmj.com/ duration of follow up. Multivariate analy- reports colon cancer as well as all other types sis with adjustment for cholecystectomy of cancer among more than 40 000 gall stone and clinically defined obesity did not patients both with and without cholecystec- change these estimates to any significant tomy in a large population based design. The extent. Excess risks were found for cancers analyses included information on a diagnosis of of the and the small intestine. A pancreas obesity. on September 25, 2021 by guest. Protected copyright. non-significant increased risk for breast Danish Cancer cancer was seen in women five years after Society, Division for initial discharge for gall stones. Methods Cancer Epidemiology, Copenhagen, Denmark Conclusion-A borderline significant as- The study population consisted of patients C Johansen sociation was seen between gall stones and who had been discharged from hospital with a L Mellemkjaer cancer of the colon, and for cancer of diagnosis ofgall stones in 1977-1989. In 1977, G Engholm J H Olsen pancreas and small intestine as well as for the Danish National Board of Health esta- breast cancer in women. blished a population based Hospital Discharge Epidemiology and (Gut 1996; 39: 439-443) Register, which keeps records of more than Biostatistics Program, Division of Cancer 99% of all hospital discharges for somatic Etiology, National Keywords: gall stones, cholecystectomy, obesity, diseases.22 The information on each discharged Cancer Institute, colorectal cancer. patient includes the personal identification Bethesda, Maryland, a 10 USA number, which is unique digit number for Wong-Ho Chow every Danish citizen, date of discharge, and up Reports of high faecal excretion of bile acids to 20 diagnoses per discharge, classified Surgical Department and bile derivatives by patients with colorectal according to a Danish modification of the K, Bispebjerg Hospital, University of cancer and those with cholecystectomy' 2 have International Classification of Diseases, eighth Copenhagen, intensified research into the relation between revision (ICD-8).23 In addition, surgical pro- Copenhagen, Denmark gall stones and colorectal cancer. Several cedures are recorded and classified according T Jorgensen studies of gall stone patients have been to the Danish Classification of Surgical Pro- Correspondence to: Dr C Johansen, reported3-12; most showed a positive asso- cedures and Therapies.2' Danish Cancer Society, ciation with cancer of the colon, with relative All discharge records for 1977-1989 that Division for Cancer Epidemiology, risks of 1-2-2.4. In the studies that showed an included a diagnosis of cholecystolithiasis Strandboulevarden 49, effect and provided data on risk by anatomical (ICD-8: 574.00) or cholelithiasis (574.09) DK-2100 Copenhagen 0, Denmark. subsite, the risk was generally greater for were abstracted. For patients who had been Accepted for publication cancer of the proximal colon than for other discharged more than once with such a 18 April 1996 parts of the colon and rectum.8-12 diagnosis, the day of the first hospital discharge 440 40ohansen, Chow, J0rgensen, Mellemkjaer, Engholm, Olsen was used as the date of entry into the cohort; numbers of cancers were compared with those it should be noted, however, that some patients expected on the basis of national incidence may have had gall stones before 1977. The full rates, which are divided into groups according discharge history of each patient was searched to sex, age, and calendar time in five year to obtain any information on a diagnosis of intervals. Gut: first published as 10.1136/gut.39.3.439 on 1 September 1996. Downloaded from obesity and cholecystectomy. Using the Multiplication of the person years under personal identification number, linkage was observation by the incidence rate yields the made to the Danish National Board of Health number of cancers that would be expected if to obtain information on vital status, and to the patients with gall stones experienced the same Danish Cancer Registry, which has been in risk as that prevailing in the general population operation since 1942, to obtain information on of Denmark. Tests of significance and 95% incident cancers.24 Of 49070 patients initially confidence intervals (CI) for the relative risk - identified in the Hospital Discharge Register, that is, the ratio of observed to expected we excluded 3654 (7.4%) patients who had a cancers, were computed on the assumption cancer of the abdominal organs or breast that the observed number of cancer cases in a before the initial hospital discharge for gall specific category follows a Poisson distribution, stones and 3318 (6.6%) who died during the using Byar's approximation.25 Risks were esti- first year of follow up, leaving 42 098 patients mated separately for patients with and without for the study (Table I). Among them, 72% had a cholecystectomy, as well as for the entire cholecystectomy, and 95% of which were cohort combined. In addition, the effect of performed within a year of the index gall stone cholecystectomy, obesity, sex, age at diagnosis diagnosis. of gall stones and latency since first discharge Patients were followed up for cancer with a gall stone diagnosis were adjusted for in occurrence from one year after discharge for multiplicative Poisson regression models that gall stones until the date of death or the end incorporated the national rates as the stan- of 1992, whichever came first. The observed dard,26 using the Epicure statistical package.27 As the risks were not affected substantially by adjustment for these factors, only results TABLE I Descriptive characteristics ofpatients with a diagnosis ofgall stones at hospital adjusted for age, sex, and calendar years will be discharge, Denmark, 1977-89 presented in the Tables. Characteristic Men (%) Women (%) Both sexes (%) (n="10 904) (n=31 194) (n=42 098) Period of diagnosis Results 1977-80 31-3 33-3 32-8 1981-84 30-8 30.7 30.7 The 42098 gall stone patients included in the 1985-89* 37-8 36-0 36-5 study accrued 312784 person years of follow Age at discharge (y) <30 2-3 9-8 7-8 up, with an average of 7.4 years each (range, 30-39 7-2 12-5 111 1-16 years). The median age at the entry in the http://gut.bmj.com/ 40-49 13-2 14-1 13-9 50-59 20-0 18-2 18-7 cohort was 63 years for men and 57 years for 60-69 26-7 19 9 21-6 women. The male to female ratio was 0.4. A .70 30-6 25-6 26-9 Cholelithiasis with cholecystectomy 67-5 74-1 72-4 diagnosis of obesity was noted in 2190 (5.2%) Cholelithiasis without cholecystectomy 32-5 25-9 27-6 patients (Table I). Record of obesityt 3-2 5-9 5-2 Overall, 3940 cancers were observed com- *Includes five years. tA diagnosis of obesity stated in any of the hospital discharge records of the pared with 3670 expected, yielding a small but patient. significantly increased relative risk of 1.07 on September 25, 2021 by guest. Protected copyright. (Table II), 1.07 in men and 1P08 in women. TABLE iI Observed and expected numbers ofcancer* among 42 098 patients with a The increase was due mainly to slight but diagnosis ofgall stones on their discharge record, Denmark, 1977-89 statistically significant increases in the risk for Site Observed Expected RRt 95% CI non-melanoma skin cancer (RR, 1.04), cancers of the breast (1-05), colon (1.09; 1.17 in men All neoplasms 3940 3670 1-07 1-0 to 1 1 Buccal cavity and pharynx 74 59-2 1-25 10 to 1-6 and 1.06 in women), kidney (1P21), buccal Oesophagus 41 30-6 1-34 1O to 1-8 cavity and pharynx (1P25), pancreas (1.33), Stomach 118 110-1 1-07 0.9 to 1-3 Small intestine 23 8-8 2-60 1-6 to 3-9 and oesophagus (1.34), and of leukaemia Colon 360 329-9 1-09 1Oto 1-2 (1 35).
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