EDITORIALS

The Rising Incidence of Gastric Cardia Cancer

Susan S. Devesa, Joseph F. Fraumeni, Jr.

Affiliation of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.

Correspondence to: Susan S. Devesa, Ph.D., National Institutes of Health, Executive Plaza South, Rm. 8048, Bethesda, MD 20892.

Recent estimates of global cancer statistics have ranked stomach cancer behind only lung cancer in the number of new cases and deaths worldwide (1). Incidence and mortality rates for stomach cancer in the United States and developed countries of Europe have decreased steadily for many years, while the rates still remain considerably higher in many developing countries (2-5). In the face of the overall decline in stomach cancer, a number of investigators around the world have reported rising incidence rates for gastric cardia adenocarcinoma, almost always in conjunction with increases in esophageal adenocarcinoma (6-15). In the United States, based on data from the Surveillance, Epidemiology, and End Results (SEER)1 program, incidence rates for both gastric cardia and esophageal adenocarcinomas have increased 4%-10% per year among men since 1976, more rapidly than for any other type of cancer (6). In recent years, the incidence of gastric cardia adenocarcinoma in the United States among white males has nearly equaled the rate for noncardia gastric tumors (7). In Sweden, the incidence of gastric cardia carcinoma since 1970 has shown a mean annual increase of 2.5% (11).

In this issue of the Journal, Ekstrom et al. (16) investigate whether variations in the diagnosis, classification, and reporting of gastric cancer in Sweden might have affected the observed increase in the incidence of cardia tumors. They used data from a case-control study in which gastric cancer cases diagnosed from 1989 through 1994 were identified and compared with those routinely reported to the Swedish Cancer Registry. The study procedures included detailed rules for examining medical records and review of all available histologic slides by an experienced pathologist. The distance from the cardioesophageal junction was used to define cancers arising in the gastric cardia (17). Compared with the "gold standard" of information obtained from the case-control study, Ekstrom et al were able to quantify the degree to which gastric cardia adenocarcinomas were misclassified over the time period. In particular, the inclusion of false positives and the missing of true cases in the registry raised concerns that misclassification may have contributed to the upward trends observed for gastric cardia adenocarcinoma (11), even though no variation in misclassification was detected over the relatively short period studied.

According to the most recent volume of Cancer Incidence in Five Continents (18), registration of cancer in Sweden is compulsory for physicians, hospitals, and pathologists, and case registration is estimated to be 96% complete. From 1988 through 1992, 96% or more of all stomach cancers diagnosed and reported to the Swedish Cancer Registry had microscopic verification of the diagnosis, comparable to the best population-based registries in the world. However, a relatively high proportion of cases had gastric tumors that either spanned at least two subsites or were of unspecified origin. This category accounted for 75% of gastric cancers among males and 83% among females. With increasing evidence that cardia and noncardia tumors differ in terms of environmental (7) and possibly genetic determinants (19), it seems plausible that diagnostic and reporting practices may have contributed to the observed increase in cardia tumors, but unfortunately the Ekstrom report does not provide data on the corresponding trends for noncardia gastric cancers. Indeed, it is surprising that more gastric cardia tumors were not found after careful record and pathology review, given the high proportion of cases coded to multiple or unspecified subsites. In the United States during the same period from 1988 through 1992, 25% and 32% of the total stomach cancer cases among white males and females, respectively, did not have a precisely designated subsite (18). Of these, more than one third had tumors that overlapped at least two subsites (20). The proportion of all stomach cancers among white males with unspecified subsite decreased from 38% in the 1970s to 29% in the 1980s (6). We have estimated that, if the unspecified gastric tumors were distributed anatomically in proportion to the relative frequencies of adenocarcinoma by known subsite, about one fourth of the observed increase in the incidence of gastric cardia cancer from 1976 through 1987 would have resulted from more specific diagnoses (6). Further work is needed to clarify time trends in gastric cardia and noncardia cancer around the world, but these studies are currently limited by the high proportion of unspecified gastric tumors in many population-based cancer registries (18).

The problem of distinguishing gastric cardia from noncardia adenocarcinomas is further magnified by the difficulty in separating cardia tumors from adenocarcinomas of the esophagus, an issue not addressed in the Ekstrom study. Some case-control studies of esophageal and gastric cardia adenocarcinomas have combined these tumors as a single entity (21-25), whereas others have examined them separately (26-28). Although all of these studies included a review of hospital and pathology records, only Lagergren et al. (28) mentioned using distance from the gastroesophageal junction to define cardia tumors. It is interesting that, although three authors of the Lagergren paper are also authors of the Ekstrom report, the definitions used for cardia cancer are different. Lagergren et al. (28) included as gastric cardia tumors those tumors having an estimated point of origin within 2 cm proximal or 3 cm distal to the gastroesophageal junction, whereas Ekstrom et al. (16) included those tumors centered within 1 cm proximal and 2 cm distal to the junction, citing Misumi et al. (17) as the source of their definition. It is questionable whether tumors originating proximal to the junction should be classified as cardia rather than esophageal adenocarcinoma. Thus, it appears likely that the discrepancies in site classification reported by Ekstrom et al. result in part from the diagnostic practices of Swedish clinicians and pathologists in defining tumors of the gastric cardia and in part from the lack of routine reporting of subsites to the cancer registry.

Historically, esophageal cancers were mostly squamous cell carcinomas, whereas stomach cancers were adenocarcinomas (29), with both sites being more common among African-Americans than whites in the United States (30). Epidemiologic investigations of stomach cancer have consistently identified dietary factors, such as low intake of fruit and vitamin C, and infection with Helicobactor pylori as important risk factors (5), whereas studies of esophageal cancer have implicated cigarette smoking and heavy alcohol consumption as major determinants (31). Evidence is emerging, however, that gastric and esophageal tumors may be classified as at least three distinct etiologic forms of cancer. Although incidence rates for noncardia gastric tumors and (to a lesser extent) esophageal squamous cell carcinomas have steadily declined, the incidence of gastric cardia and esophageal adenocarcinomas has risen in the United States, especially among white males (6,7). The temporal and racial patterns by subsite and cell type are so pronounced that it seems very unlikely that diagnostic and reporting practices play a major role in the rising incidence of gastric cardia or esophageal adenocarcinomas. In addition, recent analytic studies have revealed a similar array of risk factors, with gastroesophageal reflux disease and subsequent Barrett's esophagus as predisposing conditions for both tumors (23,28). Cigarette smoking is also linked to these tumors, although the risks are lower than for esophageal squamous cell carcinoma and persist longer after smoking cessation (21,22,24,26,32-34). In addition, obesity has emerged as an important risk factor (27,33,35), perhaps by increasing intra-abdominal pressure and subsequent reflux disease (23,36-38). Although Helicobacter pylori infection plays an important role in noncardia gastric cancer, there is some evidence that cagA+ strains may have an inverse relation to gastric cardia and esophageal adenocarcinomas (39-42). A variety of other risk factors are under active investigation to identify reasons for the upward incidence trends in both tumors.

By their careful study of incidence data for gastric cardia cancer in Sweden, Ekstrom et al. (16) have illustrated the need to evaluate the specificity and accuracy of diagnoses in interpreting the rising trend, which corresponds in other populations to marked increases in esophageal adenocarcinoma. With improvements in the quality of data collected by cancer surveillance systems in various countries, it should be possible to limit the potential sources of bias and error, and thus to identify temporal and other patterns of cancer that give rise to etiologic hypotheses.

NOTES

1 SEER is a set of geographically defined, population-based central tumor registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Each registry annually submits its cases to the NCI on a computer tape. These computer tapes are then edited by the NCI and made available for analysis. Back

REFERENCES

1 Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999;49:33-64.[Abstract/Free Full Text]

2 Devesa SS, Silverman DT. Cancer incidence and mortality trends in the United States: 1935-74. J Natl Cancer Inst 1978;60:545-71.[Medline]

3 Devesa SS, Silverman DT, Young JL Jr, Pollack ES, Brown CC, Horm JW, et al. Cancer incidence and mortality trends among whites in the United States, 1947-84. J Natl Cancer Inst 1987;79:701-70.[Medline]

4 Devesa SS, Blot WJ, Stone BJ, Miller BA, Tarone RE, Fraumeni JF Jr. Recent cancer trends in the United States. J Natl Cancer Inst 1995;87:175-82.[Abstract]

5 Nomura A. Stomach cancer. Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. New York (NY): Oxford University Press; 1996. p. 707-24.

6 Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1287-9.[Abstract]

7 Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998;83:2049-53.[Medline]

8 Powell J, McConkey CC. The rising trend in oesophageal adenocarcinoma and gastric cardia. Eur J Cancer Prev 1992;1:265-9.[Medline]

9 McKinney A, Sharp L, Macfarlane GJ, Muir CS. Oesophageal and gastric cancer in Scotland 1960-90. Br J Cancer 1995;71:411-5.[Medline]

10 Moller H. Incidence of cancer of oesophagus, cardia and stomach in Denmark. Eur J Cancer Prev 1992;1:159-64.[Medline]

11 Hansson LE, Sparen P, Nyren O. Increasing incidence of carcinoma of the gastric cardia in Sweden from 1970 to 1985. Br J Surg 1993;80:374-7.[Medline]

12 Hansen S, Wiig JN, Giercksky KE, Tretli S. Esophageal and gastric carcinoma in Norway 1958-1992: incidence time trend variability according to morphological subtypes and organ subsites. Int J Cancer 1997;71: 340-4.[Medline]

13 Levi F, Randimbison L, La Vecchia C. Esophageal and gastric carcinoma in Vaud, Switzerland, 1976-1994 [letter]. Int J Cancer 1998;75:160-1.[Medline]

14 Thomas RJ, Lade S, Giles GG, Thursfield V. Incidence trends in oesophageal and proximal gastric carcinoma in Victoria. Aust N Z J Surg 1996;66:271-5.[Medline]

15 Armstrong RW, Borman B. Trends in incidence rates of adenocarcinoma of the oesophagus and gastric cardia in New Zealand, 1978-1992. Int J Epidemiol 1996;25:941-7.[Abstract]

16 Ekstrom AM, Signorello LB, Hansson LE, Bergstrom R, Lindgren A, Nyren O. Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence. J Natl Cancer Inst 1999;91:786-90.[Abstract/Free Full Text]

17 Misumi A, Murakami A, Harada K, Baba K, Akagi M. Definition of carcinoma of the gastric cardia. Langenbecks Arch Chir 1989;374:221-6.[Medline]

18 Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J, editors. Cancer incidence in five continents, Vol. VII. Lyon: International Agency for Research on Cancer; 1997.

19 Palli D, Bianchi S, Decarli A, Cipriani F, Avellini C, Cocco P, et al. A case-control study of cancers of the gastric cardia in Italy. Br J Cancer 1992;65:263-6.[Medline]

20 Surveillance, Epidemiology, and End Results (SEER) Program Public-Use CD-ROM (1973-1995), National Cancer Institute, DCCPS, Surveillance Program, Cancer Statistics Branch, released April 1998, based on the August 1997 submission.

21 Gray JR, Coldman AJ, MacDonald WC. Cigarette and alcohol use in patients with adenocarcinoma of the gastric cardia or lower esophagus. Cancer 1992;69:2227-31.[Medline]

22 Kabat GC, Ng SK, Wynder EL. Tobacco, alcohol intake, and diet in relation to adenocarcinoma of the esophagus and gastric cardia. Cancer Causes Control 1993;4:123-32.[Medline]

23 Chow WH, Finkle WD, McLaughlin JK, Frankl H, Ziel HK, Fraumeni JF Jr. The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia. JAMA 1995;274:474-7.[Abstract]

24 Zhang ZF, Kurtz RC, Sun M, Karpeh M Jr, Yu GP, Gargon N, et al. Adenocarcinomas of the esophagus and gastric cardia: medical conditions, tobacco, alcohol, and socioeconomic factors. Cancer Epidemiol Biomarkers Prev 1996;5:761-8.[Abstract]

25 Zhang ZF, Kurtz RC, Yu GP, Sun M, Gargon N, Karpeh M Jr, et al. Adenocarcinomas of the esophagus and gastric cardia: the role of diet. Nutr Cancer 1997;27:298-309.[Medline]

26 Gammon MD, Schoenberg JB, Ahsan H, Risch HA, Vaughan TL, Chow WH, et al. Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 1997;89:1277-84.[Abstract/Free Full Text]

27 Chow WH, Blot WJ, Vaughan TL, Risch HA, Gammon MD, Stanford JL, et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 1998;90:150-5.[Abstract/Free Full Text]

28 Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825-31.[Abstract/Free Full Text]

29 Thomas RM, Sobin LH. Gastrointestinal cancer. Cancer 1995;75(1 Suppl):154-70.[Medline]

30 Ries LA, Kosary CL, Hankey BF, Miller BA, Edwards BK, editors. SEER cancer statistics review, 1973-1995. Bethesda (MD): National Cancer Institute; 1998; NIH Publ No. 98-2789.

31 Blot WJ. Esophageal cancer trends and risk factors. Semin Oncol 1994;21:403-10.[Medline]

32 Brown LM, Silverman DT, Pottern LM, Schoenberg JB, Greenberg RS, Swanson GM, et al. Adenocarcinoma of the esophagus and esophagogastric junction in white men in the United States: alcohol, tobacco, and socioeconomic factors. Cancer Causes Control 1994;5:333-40.[Medline]

33 Vaughan TL, Davis S, Kristal A, Thomas DB. Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 1995;4:85-92.[Abstract]

34 Garidou A, Tzonou A, Lipworth L, Signorello LB, Kalapothaki V, Trichopoulos D. Life-style factors and medical conditions in relation to esophageal cancer by histologic type in a low-risk population. Int J Cancer 1996;68:295-9.[Medline]

35 Brown LM, Swanson CA, Gridley G, Swanson GM, Schoenberg JB, Greenberg RS, et al. Adenocarcinoma of the esophagus: role of obesity and diet. J Natl Cancer Inst 1995;87:104-9.[Abstract]

36 Hogan WJ, Dodds WJ. Gastroesophageal reflux disease (reflux esophagitis). Sleisenger MH, Fordtran JS, editors. Gastrointestinal disease. 4th ed. Philadelphia (PA): W. B. Saunders; 1989. p. 594-619.

37 Day JP, Richter JE. Medical and surgical conditions predisposing to gastroesophageal reflux disease. Gastroenterol Clin North Am 1990;19:587-607.[Medline]

38 Reid BJ, Barrett MT, Galipeau PC, Sanchez CA, Neshat K, Cowan DS, et al. Barrett's esophagus: ordering the events that lead to cancer. Eur J Cancer Prev 1996;5 Suppl 2:57-65.

39 Hansson LR, Engstrand L, Nyren O, Lindgren A. Prevalence of Helicobacter pylori infection in subtypes of gastric cancer. Gastroenterology 1995;109:885-8.[Medline]

40 Martin-de-Argila C, Boixeda D, Redondo C, Alvarez I, Gisbert JP, Garcia Plaza A, et al. Relation between histologic subtypes and location of gastric cancer and Helicobacter pylori. Scand J Gastroenterol 1997;32:303-7.[Medline]

41 Wu MS, Chen SY, Shun CT, Lee WJ, Wang HP, Wang TH, et al. Increased prevalence of Helicobacter pylori infection among patients affected with intestinal-type gastric cancer at non-cardiac locations. J Gastroenterol Hepatol 1997;12:425-8.[Medline]

42 Chow WH, Blaser MJ, Blot WJ, Gammon MD, Vaughan TL, Risch HA, et al. An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res 1998;15:588-90.


This article has been cited by other articles in HighWire Press-hosted journals:


             
Copyright © 1999 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement