Tobacco smoking and alcohol consumption as risk factors for thymoma – A European case-control study
Introduction
Thymomas are rare tumours originating from thymic epithelial cells, i.e. from the thymus. Thymomas are most often encapsulated benign tumours, but must always be regarded as potentially malignant with possibility of invasiveness, metastatic spread and recurrences. The most common site for metastases is pleura. Some of them are obviously well differentiated carcinomas. The WHO classification separates five categories: medullary, lymphocyte-rich, cortical, mixed, and well differentiated thymic carcinomas [1,2]. The incidence of thymoma in Europe and in the USA is approximately 0.1-0.3 per 100 000 in males and females. Most cases occur between 40 and 60 years of age [3,4]. Thymus is an important part of the immune system, and there is a well-known association between thymoma and autoimmune disease, especially myasthenia gravis, recently iterated in a study of 85 cases of thymoma [5]. However, thymoma is considered as the causal factor of these disorders, with disappearing of symptoms if the tumour is operated.
Very little is known about the aetiology of thymoma. EBV infection has been reported as a suspect risk factor for thymic carcinomas in some studies as reviewed by Sweeney et al. [3], also including reports that the EBV genome is present in thymomas occurring in Chinese patients. A Japanese report describes a case of suspected causal relationship between HTLV-1 carrier state and thymoma [6]. Furthermore, a case of thymoma among 49 different tumours in a group of patients with HIV infection is reported from Italy [7]. In a register study from England and Wales, not separating thymomas from thymic carcinomas, a birth cohort analysis showed the lowest risk for persons born during the Second World War [8]. Irradiation may be of etiologic interest shown by some reports of synchronous thyroid and thymic malignancy following childhood irradiation [9]. Very few papers report anything about chemical exposures and thymoma. Animal studies have shown that vinyl carbamate may induce thymomas if administered in the first weeks after birth [10]. One case report describes a case of thymoma in a worker exposed to fluorocarbons in an automobile plant [11]. A case series from France with 37 patients with thymic carcinoma showed that half of them (19/37) were smokers, indicating tobacco as a possible risk factor [12].
Since very little is known about risk factors, we performed the first case-control study on this disease, focusing upon life-style factors and occupational exposures. In this paper we present data regarding tobacco and alcohol consumption in relation to thymoma.
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Material and methods
This study was a part of a large multi-centre case-control project conducted in ten European countries and including seven different rare tumours, among them thymoma, using a large common control group for all the different tumour sites. The project, which has been described in detail in earlier reports [[13], [14], [15], [16]], aimed at including enough cases of the rare tumours investigated by a multi-national effort.
In the thymoma study, cases and controls from the following regions in seven
Results
In total, 120 thymoma cases were recruited from seven countries (Sweden, Denmark, France, Germany, Italy, Spain, and Portugal), Table 1. Five of these cases (4%), however, were judged as not eligible by the reviewing pathologist and were excluded from analyses. Of the 115 remaining cases, 93 were classified as "definite" and 22 as "possible". In the latter category the main part, 12, were cases with a definite histopathologic report but without any available slide to review because of refusal
Discussion
To our knowledge, no previous epidemiological studies have been made focusing on potential risk factors for thymoma. As a consequence, there are hardly any hypotheses regarding aetiologic factors of importance for this tumour. The obvious reasons for this lack of research concern the rarity of the disease and the heterogeneous pathology with a range from clearly benign tumours through potential malignant thymomas to thymic carcinomas.
The advantage of this study is the large number of
Contribution
Study concepts: M.E., L.K., N.A., W.A., P.G., F.M., M.M.S.-V., S.S.
Study design: M.E., L.K., N.A., W.A., P.G., F.M., M.M.S.-V., S.S.
Data acquisition: All
Quality control of data and algorithms: M.E., L.K.
Data analysis and interpretation: M.E., L.K., N.A., W.A., P.G., F.M., M.M.S.-V., S.S.
Statistical analysis: M.E., L.K.
Manuscript preparation: M.E., L.K.
Manuscript editing: All.
Manuscript review: All.
Acknowledgements
We gratefully acknowledge collaboration from patients, control persons, participating hospitals, and data providers.” Occupational risk factors for rare cancers of unknown aetiology” was supported financially by the European Commission, DGXII, Programme BIOMED, grant no BMH1 CT 93-1630, and national funding agencies: Denmark: The strategic Environment Programme, grant no 92.01.015.7-06, and the Danish Epidemiology Science Centre,- the activities of the centre are financed by a grant from the
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