Tobacco smoking and alcohol consumption as risk factors for thymoma – A European case-control study

Highlights

• Data is presented from the first analytical epidemiologic study on thymoma ever performed

• A statistically significant risk for thymoma was demonstrated among heavy smokers

• A high consumption of spirits was also significantly associated with the risk of thymoma

Abstract

Purpose

Hardly anything is known about the aetiology of thymoma. This paper presents data regarding tobacco smoking and alcohol consumption in relation to thymoma from the first case-control study performed on this rare tumour.

Methods

A European multi-centre case-control study including incident cases aged 35–69 years with thymoma between 1995 and 1997, was conducted in seven countries. A set of controls, used in seven parallel case-control studies by the same research group was used, including population-based controls from five countries and hospital controls with colon cancer from two countries. Altogether 103 cases, accepted by a reference pathologist, 712 colon cancer controls, and 2071 population controls were interviewed.

Results

Tobacco smoking was moderately related with thymoma (OR 1.4, 95% CI 0.9–2.2), and a tendency to dose-response was shown (p = 0.04), with an increased risk for heavy smokers defined as ≥41 pack-years (OR 2.1, 95% CI 1.1–3.9). A high consumption of spirits defined as ≥25 g of alcohol per day was associated with an increased risk of thymoma (OR 2.4, 95% CI 1.1–5.4), whereas no association was found with beer or wine.

Conclusions

Tobacco smoking and a high intake of spirits were indicated as risk factors for thymoma.

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.