1 School of Public Health, Department of Epidemiology and Medical Statistics, University of Bielefeld, Bielefeld; 2 World Health Organization Geneva Programme on Cancer Control, Geneva, Switzerland; 3 Medizinische Klinik II, Klinikum Aschaffenburg, Aschaffenburg, Germany
Received 2 July 2001; revised 18 December 2001; accepted 18 January 2002
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Abstract |
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While the clinical and experimental knowledge concerning gastric lymphomas is increasing, there is a scarcity of epidemiological data.
Patients and methods:
A population-based sample of patients in Franconia and Saarland in Germany was collected from a clinical trial, hospital archives and a cancer registry.
Results:
Over a period of 3 years, 94 patients with primary gastric lymphoma were recorded out of a total population of 3.5 million. The standardised incidence rates in Saarland and Franconia were 0.7 and 0.8 cases per 100 000, respectively. Patients were predominantly from higher age groups (mean age 62.1 years) and the incidence in men was slightly more than in women (P <0.03). The distribution of histological subtypes in Franconia was as follows: marginal zone B-cell lymphomas (MZBL), 58%; diffuse large-cell B-cell lymphoma (DLBL), 33%; and mixed forms, 9%. Helicobacter pylori could be detected histologically in 84% of all cases, 95% of MZBL cases and 68% of DLBL cases.
Conclusions:
Incidence rates of gastric lymphoma in Germany were similar to that in other European countries, except England, where rates are lower. The subtype-specific differences of H. pylori infection rates could be due to differences in carcinogenesis or to secondary changes during malignant transformation.
Key words: diffuse large-cell B-cell lymphoma, epidemiology, gastric non-Hodgkins lymphoma, Helicobacter pylori infection rates, incidence rates, marginal zone B-cell lymphoma
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Introduction |
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We carried out a study to determine incidence rates and clinical features, such as histological type and H. pylori status, of gastric lymphoma in Germany from a population-based sample of affected patients. The study covered a total population of 3.5 million in the state of Saarland and the districts of Lower and Upper Franconia, the latter situated in the state of Bavaria (Figure 1).
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Materials and methods |
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The quality standards of the histological diagnoses in the Franconian data sources were of the same high level. Patients in the multicentre study were only accepted for inclusion if the central histological review of the Department of Pathology at the University of Wuerzburg confirmed the collaborating centres initial diagnosis of primary gastric lymphoma. Both Departments of Pathology collaborated closely in the diagnosis of gastrointestinal lymphomas and both followed the REAL classification of NHL [10]. All cases were reviewed by H.-K. Müller-Hermelink (Department of Pathology, University of Wuerzburg) or by Stolte (Department of Pathology, Klinikum Bayreuth). Patients were included when MZBL or DLBL had been diagnosed and confirmed. Gastric lymphomas consisting of low- and high-grade components, as described and classified by de Jong (type B and type C) [16], were also included. Copies of the patients histological records were provided by the Departments of Pathology as well as the multicentre study archive. From these records clinical data were abstracted, such as H. pylori infection status by histological diagnosis. The data from the different Franconian sources were compared to eliminate duplication.
In order to obtain incidence rates for gastric lymphomas from another region, we analysed data provided by the Saarland Cancer Register, an official population-based cancer register which covers the states total population of 1.08 million. There are multiple, partly overlapping sources of notifications for this register, particularly from clinicians and pathologists. The rate of case ascertainment for this register has been estimated to be high [17]. Data on patients affected by gastric lymphomas have been available since January 1994; therefore, a 3-year time period from January 1994 to December 1996 was chosen for case recruitment. In order to determine the quota of gastric lymphoma within the whole group of NHL, we requested data from the Saarland Cancer Register for the same time period. All cases of NHL classified according to the International Classification of Diseases (ICD) 9 [18] coded 200 or 202 were included.
The demographic data of the catchment population by age group for Lower and Upper Franconia were published in the statistical yearbooks of Bavaria [19]. In the case of Saarland, these data were provided by the regional cancer register.
In order to compare the H. pylori infection rates of our patient study sample with the general German population, we referred to a representative sample from western Germany for which H. pylori testing had been performed [20].
Statistical analysis
All incidence rates were referred to as the number of cases per 100 000 persons at risk. Age-specific incidence rates were calculated separately for Lower and Upper Franconia and Saarland based on the mean population of the corresponding study periods. Owing to the small number of patients only four age groups were chosen. Based on pooled data from all study regions age-specific incidence rates were calculated in 10-year intervals. The corresponding 95% confidence intervals (CIs) were computed by means of the confidence limit factors for estimates of Poisson- distributed variables [21]. Age-standardised incidence rates were calculated by direct methods based on the New European standard population and the World standard population [22]. Gender differences of regional age-specific incidence rates were tested by stratified contingency tables, referring to the procedures proposed by Breslow and Day [23] using the StatXact-4 statistical package (Cytel Software Corporation, Cambridge, MA). As higher incidence rates for gastrointestinal lymphomas have been reported in men [24], a one-sided exact P value was considered.
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Results |
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Discussion |
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In Lower and Upper Franconia, case ascertainment is also based on overlapping sources of information from pathologists (University of Wuerzburg, Bayreuth) and clinicians (co-operating clinical centres of the multicentre study). All patients residing in Franconia diagnosed during the study period could be captured by both sources. The possibility that patients residing in Franconia were diagnosed and treated outside the districts cannot be excluded. The similarity of the estimates for incidence rates in our study for the Franconian districts and for Saarland indicates that the ascertainment rates in the study regions should be at the same high level. This assumes that regional incidence rates of gastric lymphomas in this restricted geographical context are the same.
There are small differences in the time frames of data collection between Franconia and Saarland. In the Saarland Cancer Register, site-specific coding for NHL was introduced in January 1994; therefore, data collection for this region only started 9 months later than for the multicentre study. The effect of this time frame difference was considered to be negligible for our data. The published time trend analyses of gastric lymphoma in Europe show a variation ranging between no change [1, 2] up to an annual change of 6.3% [3]. Assuming the latter rate for our study regions, no substantial influence could be expected for the validity of our estimates. Time trend analysis in our study was not performed because the observation time was too short and the number of cases too small.
Compared with the incidence rates derived from the epidemiological studies on gastric NHL (Table 1) and adjusted for the different underlying standard populations, the German rates (European standard population, women 0.70, men 0.86; World standard population, women 0.38, men 0.51, total 0.45) are very similar to the results in Denmark (European standard population, women 0.59, men 0.85) [1] and USA (World standard population, total 0.41) [7], but lower than in France (World standard population, women 0.44, men 0.76) [2]. In England the annual incidence of gastric NHL is even lower than in Germany (World standard population, women 0.20, men 0.24) [3]. These findings could be partly explained by different detection procedures, but also by geographic variations of risk factors such as H. pylori prevalence. Both these facts could also explain the differences in time trends [6].
With regard to gender differences, our results confirm the findings that the incidence in men is slightly higher than in women [2, 24]. This difference could indicate that gender-specific constitutional or behavioural factors could play an aetiological role in the development of gastrointestinal lymphomas. The gender differences concerning the mean age at diagnosis could be due to the same factors or sex-specific differences in the utilisation of medical care.
Based on histological findings, the overall H. pylori infection rate in our patient sample was 84% (95% CI 75% to 93%). Ten of 66 patients (missing data for three patients) were H. pylori negative at time of diagnosis. The H. pylori infection rate in the general population of West Germany, based on serological testing of a national random sample of 1834 participants, has been reported at 58% (95% CI 54% to 62%) in the age groups >50 years of age [21]. However, the difference in infection rates may be greater than we have found: H. pylori-negative patients at the time of diagnosis may have been exposed to this risk factor prior to or in earlier stages of the disease, H. pylori having been eliminated at the later stages [9]. It is probable, therefore, that lifetime exposure of patients was underestimated by the histological findings [25].
The infection rate in MZBL, calculated separately for the two histological subtypes, was 95% (95% CI 75% to 99%), higher than in the DLBL group [68% (95% CI 41% to 95%)]. The CIs are large due to the small number of cases. Although they partially overlap, the difference in infection rates may not be a random occurrence. Two hypotheses can be deduced. (i) In DLBL the secondary elimination of H. pylori could be more important than in MZBL due to less favourable local conditions in the stomach during the malignant transformation to high-grade lymphoma. (ii) H. pylori could also have different roles in the pathogeneses of the two subtypes of gastric lymphoma, explaining, in part, the observed difference in infection rates. Further studies on this topic should include serological findings, as they reflect a more valid assessment of the history of H. pylori infection in patients. Because H. pylori infection in the general German population is common but gastric lymphoma is a very rare disease, further research should focus on risk factors other than H. pylori. Some evidence concerning pesticides and solvents [26], dietary compounds [27] or infectious agents such as Helicobacter heilmanii [28] has been presented in the literature. Additionally, host factors could also affect gastric lymphoma risk and should be further addressed.
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Acknowledgements |
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Footnotes |
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References |
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