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The Epidemiology of Cancer of the Small Bowel

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The Epidemiology of Cancer of the Small Bowel Vol. 7, 243-251, March /998 Cancer Epidemiology, Biomarkers & Prevention 243 Review The Epidemiology of Cancer of the Small Bowel Alfred I. Neugut,’ Judith S. Jacobson, Sung Suh, Introduction Raja Mukherjee, and Nadir Arber Most biomedical research reports and review articles begin by Department of Medicine, College of Physicians and Surgeons, Columbia invoking the high incidence, mortality, or morbidity associated University, New York, New York 10032 [A. I. N., N. A.]; Division of with the disease under consideration. Cancer of the small bowel Epidemiology. School of Public Health, Columbia University, New York, New has a claim on our interest for the opposite reason. Although York [A. I. N., J. S. J., S. S., R. M.]; and Department of Gastroenterology, Tel located between the stomach and the large bowel, two of the Aviv Medical Center, Tel Aviv, Israel [N. A.] world’s most common cancer sites, the small bowel rarely develops a malignancy. However, in the United States and other countries in recent years, incidence rates of this cancer have Abstract been rising. Despite its anatomical location between two regions of Contrary to what its name implies, the small bowel con- stitutes 75% of the length of the alimentary tract and 90% of its high cancer risk, the small bowel rarely develops a mucosal surface area; yet in most industrialized countries, it is malignant tumor. However, in recent years, small bowel the site ofless than 5% of G12 malignancies (1-5). In the United cancer incidence rates have begun to rise. The purpose of States, 13 1 ,200 large bowel cancers and 22,400 stomach can- this review is to explore the descriptive and analytic cers but only 4,900 small bowel cancers are expected to have epidemiology of small bowel cancer for those factors that been diagnosed in 1997 (6). Clearly, the small bowel has some protect this organ and those factors associated with loss protection against cancer that adjacent organs lack. Studying of this protection. this protection and its failures may lead to preventive strategies Within the small intestine, the sites at the highest against cancer in other organs of the GI tract or elsewhere in the risk are the duodenum, for adenocarcinomas, and the human body. ileum, for carcinoids and lymphomas. In industrialized countries, small bowel cancers are predominantly Clinical Characteristics adenocarcinomas; in developing countries, lymphomas are much more common. The incidence of small bowel Small bowel cancer has been the subject of only six population- based descriptive epidemiological studies, each covering at cancer rises with age and has generally been higher least a decade’s accumulation of cases (2, 7-1 1). Hospital case among males than among females. series, also accumulated over decades, are therefore an impor- The risk factors for small bowel cancer include tant source of descriptive data about this rare cancer (3, 4, dietary factors similar to those implicated in large bowel 12-37). Although not population-based, these reports collec- cancer, cigarette smoking, alcohol intake, and other tively describe cases seen in hospitals around the world, and medical conditions, including Crohn’s disease, familial most of them provide more detail than is available from most adenomatous polyposis, cholecystectomy, peptic ulcer registries. disease, and cystic fibrosis. The protective factors may Approximately two-thirds of small bowel tumors are ma- include rapid cell turnover, a general absence of bacteria, lignant; more than 95% of these are adenocarcinomas, carci- an alkaline environment, and low levels of activating noids, lymphomas, or sarcomas. As Tables 1-3 indicate, the enzymes of precarcinogens. histology of these tumors is highly correlated with the anatomic Adenocarcinomas of the small and large bowel are subsite in which they arise. Adenocarcinomas, the most com- similar in risk factors and geographic distribution but not mon histological type in most Western populations, are pre- in recent time trends; colorectal cancer incidence rates in dominantly duodenal; carcinoids and lymphomas are predom- the United States have been falling since the mid-1980s. inantly ileal or jejunal. Sarcomas are more evenly distributed Small bowel lymphoma may be associated with infectious throughout the small bowel. agents, such as HIV. Given the differences in anatomic One reason why adenocarcinomas tend to arise in the duo- and geographic location among histological subtypes, denum may be that it is close to the ampulla of Vater. Although much may be learned from well-designed, histology- ampullary carcinomas are usually classified as tumors of the ex- specific epidemiological and genetic studies of cancer of trahepatic biliary tract rather than the small bowel, duodenal ad- the small bowel. enocarcinomas tend to cluster in the periampullary region. This clustering may implicate bile or its metabolites in the etiology of adenocarcinomas at this site (1 , 2, 38). However, among patients with Crohn’s disease, which generally affects the ileum rather than the more proximal small bowel, adenocarcinomas tend to occur in Received 7/25/97; revised I 2/8/97; accepted 12/18/97. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 2 The abbreviations used are: GI, gastrointestinal; SEER, Surveillance, Epidemi- I To whom requests for reprints should be addressed, at Division of Oncology, Columbia-Presbyterian Medical Center, 630 W. 168th Street, New York, NY ology and End Results; OR, odds ratio; CI, confidence interval; FAP, familial I0032. adenomatous polyposis; RR, risk ratio. Downloaded from cebp.aacrjournals.org on October 2, 2021. © 1998 American Association for Cancer Research. 244 Review: Epidemiologr of Cancer of the Small Bowel Table I Distribution of small bowel cancer b y histology. anatomic su bsite, and sex in po pulation-base d studies Anatomic subsite b Sex Incidence Population/period (Ref.) Histology Total . y . Histology Duodenum Jejunum Ileum NOS” Male Female million Los Angeles County” Adenocarcinoma 213 108 78 47 446 37.5 209 237 1972-1985 (2) Carcinoid 22 43 307 131 503 42.3 204 299 Sarcoma 22 45 35 50 152 12.8 54 98 Lymphoma 7 17 37 28 89 7.5 34 55 Total 264 213 457 256 1190 501 689 Nine SEER registries’ Adenocarcinoma 310 208 123 91 732 40.0 384 348 3.9 1973-1982 (7) Carcinoid 19 36 361 126 542 29.6 277 265 2.9 Sarcoma 26 70 51 85 232 12.7 119 113 1.2 Lymphoma II 72 126 103 312 17.0 193 119 1.6 Total 366 386 661 405 1832 973 845 9.6 Cancer registries of British Adenocarcinoma 215 115 63 128 521 41.9 Columbia. Alberta, Saskatchewan, Carcinoid 9 21 197 107 334 26.8 and Manitoba” Sarcoma 14 36 27 63 140 11.3 1975-1989 (8) Lymphoma 25 35 59 125 244 19.6 Total 263 207 346 423 1 244 682 562 1 1.0 Utah Cancer Registry’ Adenocarcinoma 29 16 13 22 80 24.4 53 27 3.0 1966-1990 (9) Carcinoid 5 17 63 51 136 41.5 84 52 6.5 Sarcoma 3 5 II 17 36 11.0 24 12 1.5 Lymphoma 5 17 20 30 72 22.0 48 24 2.5 Total 42 55 107 120 328 209 115 14.0 Nine SEER registries Adenocarcinoma 777 376 251 205 1609 842 767 6.5 1973-1991 (10) Carcinoid 114 125 951 493 1683 888 795 6.5 Total 891 501 1202 698 3292 1730 1562 13.0 a NOS, not otherwise specified. I, Total includes 20 tumors with other histologies. , Total includes 14 tumors with other histologies. ‘I Total includes 5 tumors with other histologies. Total includes 4 tumors with other histologies. I Figures exclude lymphomas and sarcomas. the ileum (39, 40), suggesting that inflammation may increase risk populations. This correlation has become weaker in the past for these cancers. two decades.3 In most industrialized countries, small bowel lymphoma is Sex Differences. In most population-based registries, males relatively rare, arises mainly in the ileum, resembles the other have higher small bowel cancer incidence rates than females histological types of small bowel cancer in its association with (50). In three of four United States population-based studies, age, and has relatively good survival (41-43). However, in the male to female ratio of cases was elevated for all four main other parts of the world, lymphoma is the most common type of histological subgroups (Refs. 2, 7, 9, 10; Table I). In this small bowel cancer, may arise anywhere in the small bowel, is respect, small bowel cancer is similar to colorectal and stomach a disease of young adults, and has relatively poor survival (14, cancer (Ref. S 1 ; Table 4). 44-48). In industrialized countries, lymphoma of the small Age Distribution. Like the incidence of colorectal and stom- bowel is often grouped with other lymphomas and excluded ach cancer, the incidence of small bowel cancer rises with age from small bowel cancer studies. The small bowel lymphomas (1). The mean age at diagnosis is typically about 60 ± 10 years of developing countries and the Mediterranean region are often (Table 2) and is largely consistent across histological subtypes associated with immunoproliferative small intestinal disease in Western populations. However, the age at diagnosis of ad- (49). enocarcinoma tends to be somewhat older and that of lym- phoma somewhat younger than those of other subtypes. Descriptive Epidemiology Race Distribution. Few data are available on the race distri- Geographical Distribution. The incidence rate of small bowel bution of small bowel malignancies within countries. Analyses cancer varies among populations. The geographic distribution of SEER data (7, 10, 1 1) and a review of the Los Angeles of this cancer differs from those of both stomach cancer (high County Cancer Surveillance Program (2) indicate a somewhat in Asian and Latin American countries and low among United higher incidence of adenocarcinoma and malignant carcinoid States whites) and large bowel cancer (high in the United States tumors in blacks (4.
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