Our results indicate the presence of significant epidemiological differences between adenocarcinoma of the oesophagus and that of the gastric cardia. While the incidence of OA continues to rise in the USA, the incidence of adenocarcinoma of the cardia remained stable between 1987 and 1996. Compared with Black men, White men have approximately five times the incidence of OA but only twice the incidence of adenocarcinoma of the cardia. Concomitant with its rising incidence, OA has also significantly increased among relatively younger ages. In all age groups, the more recently born cohorts have seen a progressive rise in the incidence of OA. Such a birth cohort effect is not seen in patients with adenocarcinoma of the cardia which has remained predominantly an affliction of patients older than 65 years.
The distinction between the two diseases can be difficult, particularly in cases where the tumour involves the gastro-oesophageal junction. The way these two malignancies are coded in the 9th revision of the Clinical Modification of the International Classification of Diseases
(ICD-9-CM), the most commonly used disease classification in the USA, has added to the difficulty of studying them separately. In the ICD-9 CM, both malignancies are grouped together under the same code (150.0).18
Unlike the ICD-9 CM, adenocarcinoma of the cardia and the oesophagus in the current study are distinctly classified into separate ICD-O codes that are based on specific morphological as well as histological features.15
This data source has distinct advantages over mortality or hospitalisation data contained in administrative databases where distinguishing between cancer types is not the primary purpose of the database. Nevertheless, tumour classification remains the major concern in interpreting the present results. It is often difficult, and occasionally impossible, to make a clear distinction between these tumours; such a problem cannot be solved by the available databases.
A shift in the classification as well as misclassification of gastro-oesophageal malignancies may have resulted in temporal changes in their incidence rates that are not representative of changes in the true occurrence of these cancers. For example, improved diagnostic accuracy using endoscopy and autopsy may have led to diagnosing more cases of OA that would have been labelled in the past as adenocarcinoma of the cardia. However, the rates of GCA between 1987 and 1996 have levelled off while rates of OA have increased, making reclassification an unlikely cause of the observed trends in OA. Furthermore, a reclassification bias typically results in a rapid increase followed by a plateau in the incidence rates once the reclassification is widely adopted. On the other hand, among White men with gastric cancer in the USA, the proportion of cancers of unspecified site decreased from 38% in the 1970s to 29% in the 1980s.1, 19
Misclassification of gastric cancer as cardia cancer might explain at least some of the results of the study. Improved diagnostic accuracy may have resulted in reclassifying some cases of “unspecific site” gastric adenocarcinoma (ICD-9 CM: 151.9)18
to adenocarcinoma of the cardia20
thus contributing to the latter cancer's early rise between 1973 and 1986 that was subsequently followed by a plateau.
The US population is aging progressively and therefore the rising rates of OA could potentially reflect an “age effect” rather than a true increase in incidence. In the current results, at least three explanations make this possibility unlikely. Firstly, the use of age adjusted incidence rates in this study mitigates this effect by adjusting for the varying age structure of the population. Secondly, an increase in incidence in younger ages has accompanied the rise in OA. Finally, the birth cohort analysis has shown clearly an increase in incidence among cohorts born more recently, irrespective of their age groups. This possible cohort effect indicates the acquisition of a risk factor early in life that increases the risk of OA in all ages of the exposed cohort.16, 17
A few previous studies distinguished between these malignancies and found some differences in their epidemiology and risk factors. Similar to our current study, Hansen et al
reported discrepancy between the temporal trends of OA and GCA incidence rates in the cancer registry of Norway.21
Between 1982 and 1992, the age adjusted rates of OA in Norway had an average annual increase of 17% in men and 15% in women, while proximal gastric cancer rates, including GCA, remained stable. Another large Swedish population based case control study was performed on the basis of the hypothesis that these tumours were distinct entities. The investigators used clear morphological and histological criteria to separate 189 cases with OA from 167 cases with GCA; both groups were then compared with 820 normal control subjects.10, 11
Among those with longstanding GORD and severe symptoms, the adjusted odds ratios were 43.5 (95% CI 18.3–103.5) for OA and 4.4 (1.7–11.0) for GCA compared with normal controls. In the same Swedish population, a strong dose dependent relation was found between body mass index (BMI) and OA.11
The adjusted odds ratio was 7.6 (3.8–15.2) among patients in the highest BMI quartile compared with those in the lowest. On the other hand, the odds ratio for GCA was 2.3 (1.5–3.6) in patients with the highest BMI quartile compared with those with the lowest.11
Lastly, conflicting results on the role of tobacco and alcohol were seen between studies that examined oesophagocardiac cancers22–24
versus those examining each malignancy separately.25
These differences are further supported by recent studies that have indicated that risk factors for the precursor lesion of OA, Barrett's oesophagus, are different from those for IM of the gastric cardia.6–8
While GORD is a strong risk factor for Barrett's oesophagus, several studies have failed to find such an association for IM of the gastric cardia. On the other hand, H pylori
infection, gastritis, and the presence of IM in the distal stomach were strong predictors of the presence of IM at the gastric cardia.6–8
The presence of H pylori
, particularly cag A+
, is inversely related to Barrett's oesophagus and OA.26, 27
Furthermore, the presence of corpus gastritis related to H pylori
reduces to a significant degree the risk of erosive oesophagitis.28–30
This might be related to reduced gastric acid secretion which renders the refluxate material less injurious among GORD patients.5
The relationship between H pylori
and adenocarcinoma of the cardia is less clear. A large US case control study reported an inverse relationship between cagA+ H pylori
and OA and GCA combined in a single group.30
In another study, Hansson et al
reported a 42% seroprevalence rate of H pylori
in patients with “gastric cardia” tumours (n=42) which was significantly lower than the 85% prevalence in gastric tumours distal to the gastric cardia. However, tumours of “gastric cardia” in the latter study were gastro-oesophageal junction tumours and hence included an unspecified number of patients with OA.31
These studies indicate that although there are obvious similarities between theses tumours, both occurring more frequently in men and Caucasians and both sharing some risk factors (GORD and obesity), there are significant differences in the magnitude of these risks as well as epidemiological variables.
It is becoming clear that when an attempt is made to separate patients with IM or adenocarcinoma at the gastro-oesophageal junction into either oesophageal or cardiac, two distinctly different groups of patients are seen. Patients with Barrett's oesophagus and/or OA are mainly White, have more GORD, less H pylori, less gastritis, and are increasing in number, especially among younger ages. On the other hand, patients with IM and/or adenocarcinoma of the gastric cardia are less likely to be White, tend to be older, have less GORD, more H pylori, more gastritis, and are not increasing in number.
In summary, we found that the rates of OA continue to rise significantly while the rise in adenocarcinoma of the gastric cardia reported earlier has ceased after 1987. Significant differences exist between OA and GCA in sex, ethnic, age, and birth cohort distribution. These differences add further evidence in support of the hypothesis that these two malignancies are two distinct disease entities.