Elsevier

Cancer Epidemiology

Volume 38, Issue 3, June 2014, Pages 273-278
Cancer Epidemiology

Familial malignant mesothelioma: A population-based study in Central Italy (1980–2012)

https://doi.org/10.1016/j.canep.2014.02.014Get rights and content

Abstract

Malignant mesothelioma is a sporadic cancer linked to asbestos exposure. Its occurrence among blood relatives (familial mesothelioma) may point to genetic susceptibility or shared exposures. The burden of the familial disease is unknown. The aims of the study were to assess at population level the proportion of familial mesotheliomas among all mesotheliomas and to investigate the family history of cancer among relatives of mesothelioma cases. We actively searched familial clusters based on a mesothelioma registry from central Italy (5.5 million people, 10% of the Italian population) of the National Mesothelioma Register network (ReNaM) as well as a pathology-based archive. Among 997 incident mesotheliomas recorded in a 32-year-period (1980–2012), we detected 13 clusters and 34 familial cases, accounting for 3.4% of all mesotheliomas. The most common clusters where those with affected siblings and unaffected parents. Asbestos exposure was occupational (n = 7 clusters), household (n = 2), environmental (n = 1), or not attributable for insufficient information (n = 3). There were 25 additional cancers in nine families. Some were cancer sites for which there is sufficient evidence (lung and larynx) or limited evidence (stomach and colon) of causal association with asbestos. The results suggest potential genetic recessive effects in mesothelioma that interact with asbestos exposure, but it is not possible to estimate the specific proportion attributable to each of these components.

Introduction

Asbestos is the well-established major aetiological risk factor for mesothelioma, a rare cancer. As the majority of common neoplasms, mesothelioma is a sporadic cancer (one individual is affected in the family). However, clusters among blood relatives (two or more affected individuals), often referred to as ‘familial’, have been reported since the 1970s [1]. It is clear that a familial aggregation of mesothelioma may simply be due to shared asbestos exposures, as reported in the vast majority of studies [1], [2], [3], [4]; however, there is the possibility that the occurrence of family clusters might be due genetic susceptibility [5]. There are several pieces of evidence that corroborate this hypothesis. Only a relatively small fraction of asbestos exposed individuals develop the disease [6], [7] and given asbestos exposure, a family history of cancer may indicate an increased susceptibility [8]. Some metabolic gene polymorphisms may modify the risk of developing mesothelioma [9], [10]. Recent genome-wide association studies have identified genetic variants associated with increased risk of malignant pleural mesothelioma [11], [12]. There are reports of this malignancy in subjects affected by rare inherited diseases, i.e., multiple exostoses [13], Li–Fraumeni syndrome [14], Marfan and Ehlers–Danlos syndromes [15], neurofibromatosis type 2 [16], familial Mediterranean fever [17] and acne inversa [18]. To-date, the evidence for a genetic predisposition is also suggested the occurrence of mesothelioma in familial cancer syndromes, as observed in carriers of TP53 [19], [20] and BRCA1 associated-protein1 (BAP1) gene mutations [21]. Finally, almost a twofold risk of mesothelioma was found in blood relatives of mesothelioma patients in the Wittenoom cohorts of workers exposed to crocidolite [22].

Because of the rarity of familial mesothelioma, there are limited epidemiological investigations and its occurrence is likely to be underestimated. The available studies have not been able to estimate the burden of familial mesothelioma, namely the proportion of cases with an affected relative (familial proportion) [23]. Among the family studies, only a few were at the population level [1], [22].

We aimed to provide epidemiological data on familial mesothelioma, taking advantage of a population-based mesothelioma registry operating in central Italy [24], covering 5.5 million inhabitants (about one tenth of the country population). This registry is part of the network of the Italian National Mesothelioma Register (ReNaM); it represents roughly one tenth of the mesothelioma burden in Italy [25]. We estimated the proportion of familial mesotheliomas in the population covered by the registry. In addition, we report the details of the familial clusters, including the generation pattern involved, and the family history of cancer.

Section snippets

Data source of cases

The mesothelioma registry of the Lazio region (including the city of Rome) (Regional Operative Center, COR-Lazio), covers for the period 2001–2012 all residents with a new diagnosis of mesothelioma and collects information on the individual exposure to asbestos. It is based on the compulsory notification of cases and on active search also. The procedures and the criteria for assessing the level of diagnostic certainty are described in the ReNaM guidelines (//www.ispesl.it/dml/leo/download/RenamGuidelines.pdf

Results

In the 32-year-period of the study (1980–2012), we identified 34 familial mesotheliomas (13 probands) in the database of 997 cases, accounting for a familial proportion of 3.4% of all mesotheliomas. The male-to-female ratio was 1.6 among the familial cases and 2.3 among all other cases. Thirty-one were mesothelioma of the pleura and three of the peritoneum (only men). Table 1 shows that 20 cases (12 probands) were incident in the 12 years of the COR-Lazio activity 2001–2012, and 14 (1 proband)

Discussion

Our analysis of families with two or more mesotheliomas extends the limited literature on familial mesothelioma, and further defines its characteristics on a population basis. It shows a not negligible proportion (exceeding 3%) of familial mesotheliomas among a large case-series.

The majority of common cancers are sporadic, 5–10% are inherited, and 10–15% are referred to as ‘familial’ [30]. On the basis of the largest Family-Cancer Database available in the world, the proportion of familial

Conflict of interest

None of the authors have any conflicts of interest.

Acknowledgments

The authors want to thank Dr. Carolina Mensi (COR of Lombardia), Dr. Cristiana Pascucci (COR Marche), and Dr. Gert Schallenberg (COR Trento) for their helpful contribute in acquiring family data for three family clusters.

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