No further increase in the incidence of esophageal adenocarcinoma in Sweden

Authors

  • Jesper Lagergren,

    Corresponding author
    1. Department of Molecular Medicine and Surgery, Upper Gastrointestinal Research, Karolinska Institutet, Stockholm, Sweden
    2. Division of Cancer Studies, King's College London, United Kingdom
    • Department of Molecular Medicine and Surgery, Upper Gastrointestinal Research, Karolinska Institutet, Norra Stationsgatan 67, level 2, 171 76 Stockholm, Sweden
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    • Tel: + 46-8-517-760-12, Fax: + 46-8-517-762-80

  • Fredrik Mattsson

    1. Department of Molecular Medicine and Surgery, Upper Gastrointestinal Research, Karolinska Institutet, Stockholm, Sweden
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Abstract

Since 1970, the incidence of esophageal adenocarcinoma has increased rapidly in Western populations, whereas the incidences of gastric cardia and gastric non-cardia adenocarcinoma have increased moderately and declined, respectively. The Swedish Cancer Register and Total Population Register provided opportunities for a valid update of incidence trends of these tumors including the year 2008. Joinpoint regression was used to assess any shifts in trends with calendar time. The esophageal adenocarcinoma incidence reached a peak in 2005, and then showed a decrease. During the period 2001–2008, the joinpoint regression analysis indicates a virtually stable incidence (annual percentage increase 1.1, 95% confidence interval [CI] −2.7 to 5.1). The cardia adenocarcinoma incidence has slightly decreased after 1990 (annual percentage decrease −1.0, 95% CI −1.6 to −0.3). The decreasing incidence of gastric non-cardia adenocarcinoma has continued steadily during recent years (annual percentage decrease −4.9 (95% CI −5.2 to −4.7). Thus, an encouraging break in the rising incidence of esophageal adenocarcinoma has been seen in Sweden since 2005, whereas the corresponding incidences of gastric cardia and non-cardia adenocarcinoma have been stable and decreasing, respectively.

The incidence patterns of esophageal and gastric adenocarcinoma have shown striking changes with time in most Western populations. The incidence of esophageal adenocarcinoma has been rising faster than that of any other tumor in the United States and in some Western European countries since the mid 1970s, 1–3 whereas the incidence of gastric adenocarcinoma has declined steadily in these countries since the 1950s.4, 5 The incidence of cardia adenocarcinoma, located between the esophagus and the stomach, has increased, but to a more moderate level compared to esophageal adenocarcinoma, and in recent years, it has stabilized or slightly decreased.6, 7 Sweden has a nationwide, highly complete and valid cancer register, which has recently been updated to include the year 2008. The aim of this study was to provide an update of potential recent calendar period changes in the incidence pattern of adenocarcinoma arising in the esophagus and comparing it with that of the cardia, and the non-cardia part of the stomach. For completeness, we also included esophageal squamous cell carcinoma, a tumor with a slightly declining incidence in many Western populations.

Material and Methods

Data on all new cases diagnosed in 1970–2008 were obtained from the Swedish Cancer Register by year of diagnosis, sex, age at diagnosis, all tumor diagnoses and histological codes. The Swedish Cancer Register was founded in 1958. It has been validated regarding cancer of the esophagus, cardia and non-cardia area of the stomach, resulting in a completeness rate of 98% for each of these tumors. 8, 9 Since 1970, cardia adenocarcinoma has been registered as a separate diagnosis code within the stomach. We used the seventh revision of the International Classification of Diseases (ICD-7) and histology codes (PAD) to define esophageal adenocarcinoma (ICD-7 150; histology code 096), esophageal squamous cell carcinoma (ICD-7 150; histology code 146), gastric cardia adenocarcinoma (ICD-7 151.0; histology code 096) and gastric non-cardia adenocarcinoma (ICD-7 151.1, 151.8 and 151.9; histology code 096). Data on the entire Swedish population was acquired from the Total Population Register, a register with a 100% nationwide coverage. The data were stratified by sex, 5-year age groups, and by each calendar year. The annual age-standardized incidence rates per 100,000 person-years were calculated for all ages, using 5-year age groups, with the age distribution in 1989 as standard. Log-linear joinpoint regression models10 were used to detect any changes in age-standardized incidence trends with calendar time and to estimate annual percent changes in age-standardized incidence with 95% confidence intervals (CIs). Log-linear joinpoint regression models were estimated using the weighted least squares method. The number of allowed joinpoints was 0–4, with the condition of a minimum of 2 years between two joinpoints and a minimum of 3 years from a joinpoint to either end of the study period. Permutation tests were used, with a significance level of 0.05. Because of small number of cases in some strata, we also calculated age-standardized incidence rates per 100,000 person-years with 3 years moving average to reduce effects of random fluctuation. Because the patterns were similar, we chose to present annual incidence rates.

Results

During the study period, 3,510 patients were diagnosed with esophageal adenocarcinoma, 2,828 (81%) males and 682 females. The incidence of esophageal adenocarcinoma increased from 1970–1993, and the increase was further accentuated during the period 1993–2001, after which it has been virtually stable (annual percentage increase 1.1 (95% CI −2.7 to 5.1). The increase reached a peak in 2005, and during the last period, a decrease was noted (Table 1 and Figs. 1 and 2). In women, the increasing incidence of esophageal adenocarcinoma continued in a more linear manner during the entire study period (Table 1 and Figs. 1 and 2). Among 8,239 cases of esophageal squamous cell carcinoma, 5,513 males: (67%) and 2,726 females, the incidence declined after 1988 among males, while the decline has been more slight and steady among females (Table 1 and Fig. 1). The incidence of esophageal adenocarcinoma surpassed that of esophageal squamous cell carcinoma in the year 2000 in males, but not in females (Fig. 2). Among 6,243 patients with gastric cardia adenocarcinoma, 4,770 (76%) males and 1,473 females, a peak in the incidence was found in 1991 in men and in 1989 in women after which the incidence has slightly decreased (annual percentage decrease −1.0, 95% CI −1.6 to −0.3) (Table 1 and Fig. 1). The incidence of esophageal and cardia adenocarcinoma is currently similar (Fig. 1). The study included 45,671 patients with gastric non-cardia adenocarcinoma, of whom 27,188 (60%) were male and 18,483 were female. The incidence of this tumor decreased during the entire study period, and the decrease was accentuated in 1984 in both sexes after which the annual percentage decrease has been −4.9 (95% CI −5.2 to −4.7) (Table 1).

Figure 1.

a: Males and females combined, (b) males, (c) females. a–c: Age-standardized incidence of adenocarcinoma of the esophagus, gastric cardia and gastric non-cardia in Sweden per 100,000 person-years.

Figure 2.

Age-standardized incidence of esophageal adenocarcinoma and squamous cell carcinoma in men and women in Sweden per 100,000 person-years.

Table 1. Annual percent changes in age-standardized incidence with 95% confidence interval (CI) were estimated with joinpoint regression models of esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma
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To assess potential influence of other ethnicities, all analyses were repeated after having excluded patients who had immigrated (5%). These results were very similar to those including all patients (data not shown). The overall rates of tumors with unknown or undifferentiated histology were 8% for esophageal tumors, 5% for cardia tumors and 10% for gastric tumors. These rates did not substantially change with calendar time (data not shown).

Discussion

This study indicates that none of the esophageal or gastric cancer types have been increasing since 2005 in Sweden, while the most recent report from the Swedish Cancer Registry, including the years 1970–2000, concluded that the incidence of esophageal adenocarcinoma was still on the rise. 11

Among methodological issues, the complete and updated information and the nationwide coverage of the registers used are main advantages. 8, 9 Tumor misclassification regarding site, however, is a concern, particularly regarding cardia adenocarcinoma, as there are no clear anatomical borders that exactly define the location of these adenocarcinomas. This problem is shared by all studies trying to separate the sites of adenocarcinoma of the esophagus and stomach. Studies evaluating the role of such tumor misclassification have shown substantial misclassification of site, yet such misclassification did not explain the observed incidence trends.6, 8 Finally, the study population was almost entirely of Caucasian origin, which makes generalization to other ethnic groups difficult, although the exclusion of immigrants did not change the overall results.

The main result of this study is that the increasing incidence of esophageal adenocarcinoma might have come to an end must be interpreted cautiously since incidence trends may vary with time just due to chance. The finding is, however, supported by a recent study from the US including the years 1973–2006, where a the rising incidence seemed to be leveling off. 12 Our update included year 2008 and indicates that the peak has occurred. Although the decreasing incidence of gastric cancer is probably explained by changes in dietary patterns and a declining prevalence of Helicobacter pylori infection,13 the reasons for the shift in the incidence trend of esophageal adenocarcinoma are more uncertain. The prevalence rates of the main risk factors, gastroesophageal reflux and high body mass,14, 15 are rising. Similarly, the decreasing prevalence of Helicobacter pylori infection in Western populations cannot explain the decrease, because this infection is rather inversely associated with esophageal adenocarcinoma.16 A potential contributing factor, however, is the decreasing male prevalence of the risk factor tobacco smoking in Sweden.17, 18 Finally, an increased dietary intake of fruit and vegetables is a protective factor against all malignant tumors of the esophagus and stomach, which might contribute to the generally decreasing incidence of these tumors.19

In conclusion, this population-based and study with virtually 100% completeness indicates an encouraging break in the rising incidence of esophageal adenocarcinoma in Sweden since 2005, while the corresponding incidences of esophageal squamous cell carcinoma, cardia adenocarcinoma and non-cardia gastric adenocarcinoma are decreasing, stable, and have been decreasing, respectively. The results must, however, be interpreted cautiously since chance might influence these time trends.

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