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Cancers of the Pancreas and Biliary Tract: Epidemiological Considerations'

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Cancers of the Pancreas and Biliary Tract: Epidemiological Considerations' [CANCER RESEARCH35,3437-3446,November1975] Cancers of the Pancreas and Biliary Tract: Epidemiological Considerations' Joseph F. Fraumeni, Jr. Epidemiology Branch, National Cancerinstitute, NIH, Bethesda,Maryland 20014 Summary special promise in laying the groundwork for prevention of these tumors. The epidemiological patterns for pancreatic and biliary cancers reveal more differences than similarities. Pancreatic carcinoma is common in western countries, although 2 Only limited information is available on the epidemiology Polynesian groups (New Zealand Maoris and native Ha and etiology of pancreatic and biliary tract cancers. Studies waiians) have the highest rates internationally. In the into the origins of these tumors have cleanly lagged behind United States the disease is rising in frequency, predominat investigations of other tumors which are perceived as more ing in males and in blacks. The rates are elevated in urban prevalent, menacing, or fashionable for study. areas, but geographic analysis uncovered no clustering of contiguous counties except in southern Louisiana. The Pancreatic Cancer origin of pancreatic cancer is obscure, but a twofold increased risk has been documented for cigarette smokers Pancreatic neoplasms are more common than is generally and diabetic patients. Alcohol, occupational agents, and appreciated. Among deaths from malignant neoplasms in dietary fat have been suspected, but not proven to be risk the United States, pancreatic cancer is fourth on the list, factors. Except for the rare hereditary form of pancreatitis, with about 18,000 people dying each year.2 This number is there are few clues to genetic predisposition. exceeded only by the 62,000 annual deaths from lung In contrast, the reported incidence of biliany tract cancer cancer, 45,000 deaths from colonectal cancer, and 29,000 is highest in Latin American populations and American deaths from breast cancer. The 1-year relative survival rate Indians. The tumor predominates in females around the is about 8%, and the 5-year rate is about 2% (3), so that the world, except for Chinese and Japanese who show a male level of mortality is a good measure of incidence. This excess. In the United States the rates are higher in whites review is concerned with exocnine pancreatic carcinomas; than blacks, and clusters of high-risk counties have been islet cell carcinomas and other tumors comprise a very small found in the north central region, the southwest, and fraction of pancreas cancer. Appalachia. The distribution of biliary tumors parallels that Demography. There are a number of peculiarities in the of cholesterol gallstones, the major risk factor for biliary distribution of pancreatic cancer that serve as leads to cancer. Insights into biliary cancinogenesis depend upon nutritional and other etiobogical factors. Geographic differ clarification of lithogenic influences, such as pregnancy, ences are pronounced, with the frequency greatest in obesity, and hyperlipoproteinemia, exogenous estrogens, western or industrial countries. This pattern has been familial tendencies, and ethnic-geographic factors that may correlated with the prevalence of “western―diseasessuch as reflect dietary habits. Noncalculous risk factors for biliary breast cancer, colorectal cancer, and myocandial infarction cancer include ulcerative colitis, clonorchiasis, Gardner's (75). Chant 1 illustrates the international variation, with 16 syndrome, and probably certain industrial exposures. countries selected from the publication, Cancer Incidence in Within the biliary tract, tumors of the gallbladder and Five Continents (16). The rank order is determined by the bile duct show epidemiological distinctions. In contrast to male incidence, which exceeds the female rate except for the gallbladder cancer, bile duct neoplasms predominate in Latins in El Paso, Colombians, and the Bantu in South males; they are less often associated with stones and more Africa. Although the disease is common in the western often with other risk factors. In some respects, bile duct and countries, the male rates are highest among the Maonis in pancreatic tumors are alike. The male predominance of New Zealand, followed by the native Hawaiians and the both tumors, an association between cholecystectomy and black Americans. The female rates are highest among the pancreatic cancer, and other considerations have prompted native Hawaiians, followed by the Latins in El Paso and the the notion that the same biliary carcinogens may affect the Maoris in New Zealand. It is noteworthy that 2 groups of bile duct, ampulla of Vater, or, by neflux, the pancreatic Polynesian descent, the New Zealand Maonis and native duct. Various epidemiological and interdisciplinary ap Hawaiians, are especially prone to this tumor. The lowest proaches are needed to further clarify the origins of biliary rates in both sexes are reported for Nigeria and Bombay. tract and pancreatic cancers, but nutritional studies hold Table 1 presents United States mortality statistics, 1950 I Presented at the Conference on Nutrition in the Causation of Cancer, May 19 to 22, 1975, Key Biscayne, Fla. 2 Epidemiology Branch, National Cancer Institute, unpublished data. NOVEMBER 1975 3437 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1975 American Association for Cancer Research. @@@@@@ @;@cy@ @r, •:@!-@ J. F. Fraumeni, Jr. MRLES FEMALES It) 0 It) 0 @@@ It, - - iiumj Ml― 1k$@) Ml U*L*IP @l'I) ‘slut Chart I . International variation in mci I—I― dence rates for pancreas cancer (per 100,000per annum, age-standardizedto ft Pill ILITIN) world population) (16). CIII,' [“(MI lip― CILNIlI S.. 1F1IU 111111) N MUSH I U ‘lull I to 1969, for 5 racial groups.2 In both sexes blacks have Table I higher rates than whites. Among Japanese Americans, the A verage annual age-adjusted mortality rates (per /00,000) for male rate exceeds the level in blacks, while the female rates pancreas cancer in the United States by sex and race, for Japanese and Chinese Americans are lower than in 1950 to 1969 whites. American Indians have the lowest figure reported in MalesFemalesWhite9.635.83Black10.406.23Amerind6.666.03Chinese8.873.59Japanese10.645.68 males, but the female rate exceeds the level in whites (12). All racial groups show a male predominance. Factors underlying these racial differences are unclear, but an environmental influence is suggested by the much higher mortality reported for pancreatic cancer in Japanese Amen cans than in Japan (24). This shift is complicated, however, by the lack of stepwise progression; the migrants themselves have higher rates than the United States-born Japanese. A similar effect of migration within the United States is reflect in part inaccuracies in the reporting of census and suggested by a cancer mortality survey in Ohio; blacks born mortality data in the older black population. The time in the south, where the risk of pancreas cancer is low, have trends since 1950 show a 2.2-fold increase in black males, substantially higher rates than Ohio-born blacks (42). These compared to 1.9 in black females, 1.3 in white males, and trends indicate that migration from a low-risk to a high-risk 1.2 in white females. The predominance of blacks with this environment may pose an added risk, and raise the possi tumor appeared in the late 1950's and has progressively bility of a multifactorial etiology (e.g., early nutritional increased. Case-control studies of pancreas cancer in the deficits followed by dietary excesses). Another group predis black population would help identify causal factors. The posed to pancreas cancer are Jews, particularly Jewish disease is on the increase in other western countries and in women, in both the United States and Israel (76). Japan, and only part of the climb can be attributed to Chant 2 illustrates the age patterns of mortality from improvements in diagnosis and reporting (34). pancreatic cancer in the United States. The rates in blacks In contrast to the substantial international variation in predominate until age 65 and then plateau, while the rates in pancreatic cancer, geographic differences within the United whites continue to climb. This cross-over effect is seen in States are limited. Recent analyses of United States cancer reported mortality statistics for other tumors, and may mortality at the county level reveal that the highest rates for 3438 CANCER RESEARCH VOL.35 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1975 American Association for Cancer Research. Cancersof the Pancreas @nd@B1ffwty@T@ac@ 100 ‘IRLES 80 WHITES 60 40 20 . @CKS , I,― 5 15 25 35 45 55 65 75 85. Chart 2. Average annual age-specific mortality rates (per 100,000) for pancreas cancer in the United States by sex and race, 1950 to 1969. pancreatic cancer are in metropolitan areas (46). When plotted on maps (47), the areas with excessive mortality among white males or females do not cluster in a manner signifying strong occupational or other geographically re lated factors (Chart 3). An exception may be an aggregation of pancreatic cancer identified in white males from the southern part of Louisiana, where 24 of the 64 counties in the state have rates in the top 10% of the country. The geographic variation in the United States is consistent with the urban predominance of this tumor, due partly to the availability of medical services (34, 76). Most studies also indicate a positive relation to lower socioeconomic class Chart 3. Geographic variation in mortality from pancreas cancer by United States county, white males (top) and females (bottom), 1950 to (32), although the gradient is not nearly as great as for 1969. Counties are shaded according to 5 levels: (a) significantly high rates, cancers of the stomach or cervix. and in top 10%of all United States county rates; (b) significantly high Incidence data from the 1969 to 197 1 Third National rates, but not in upper decile; (c) in upper decile, but not significant; (d) not Cancer Survey (6) reveal that pancreatic cancer predomi significantly different from total United States rate; and (e) significantly nates in blacks and in males (Chart 4).
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