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Familial malignant mesothelioma

2001; Elsevier BV; Volume: 358; Issue: 9295 Linguagem: Inglês

10.1016/s0140-6736(01)06816-7

1474-547X

Rodolfo Saracci, Lorenzo Simonato,

Air Quality and Health Impacts

Michele Carbone and Joseph Testa (June 2, p 1804)1Carbone M Testa JR Genetic susceptibility and familial malignant mesothelioma.Lancet. 2001; 357: 1804Summary Full Text Full Text PDF PubMed Google Scholar envisage the probable contribution of genetic factors to asbestos-related mesotheliomas. They maintain that they showed genetic susceptibility to mesothelioma in the Cappadocian region of Turkey in a previous report,2Roushdy-Hammady I Siegel J Enri S Testa JR Carbone M Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey.Lancet. 2001; 357: 444-445Summary Full Text Full Text PDF PubMed Scopus (225) Google Scholar in which they stated “Analysis of a six-generation extended pedigree of 526 individuals showed that mesothelioma was genetically transmitted, probably in an autosomal way”. We can find no support in that report for such an assertion. First, if in the unselected entire population of the Karain and Tuzköy villages malignant mesothelioma causes 50% of deaths in men and women (for Karain this value is in line with our own data3Baris Y Simonato L Artvinli M et al.Epidemiological and environmental evidence of the health effects of exposure to erionite: a four-year study in the Cappadocian region of Turkey.Int J Cancer. 1987; 39: 10-17Crossref PubMed Scopus (211) Google Scholar), the finding that 50% of each generation was affected also within the selected subgroup of nuclear families with the disease simply corresponds to what would be expected even without genetic clustering. Second, the expected segregation ratio of affected to non-affected children for autosomal dominant transmission in a group of families with one or two parents affected—heterozygous or homozygous for the putative pathological gene—is not 1:1, but is higher. Instead, the observed segregation ratio does not diverge significantly from 1:1, which speaks, if anything, against Carbone and Testa's hypothesis. Third, 50% of the cases of mesothelioma occurred between ages 26 and 55 years, within the reproductive period. There is, therefore, a selective pressure against the permanence of a hypothetical autosomal and lethal gene at the very high frequency implied by the mesothelioma rates. Fourth, we wonder how a diagnosis of mesothelioma could be established and confirmed by review of the medical records for the six-generation extended pedigree, since records from the 19th century would be needed. Before 1978, when Baris4Baris YI Sahin AA Ozesmi M et al.An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urgup in Anatolia.Thorax. 1978; 33: 181-192Crossref PubMed Scopus (203) Google Scholar discovered the endemic, mesothelioma was diagnosed as tuberculosis, lung cancer, metastatic cancers, or other disorders. The report by Roushdy-Hammady and co-workers2Roushdy-Hammady I Siegel J Enri S Testa JR Carbone M Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey.Lancet. 2001; 357: 444-445Summary Full Text Full Text PDF PubMed Scopus (225) Google Scholar shows in pedigree B a third-generation case who died at age 61 years, and his grandfather died at 55. Even under the most favourable assumptions—death of the case in 2000, age at reproduction 17 years—the grandfather could not have died later than 1960, which is long before local recognition of the disease. As late as 1979–83, when we contributed to establishing the causal role of environmental erionite,3Baris Y Simonato L Artvinli M et al.Epidemiological and environmental evidence of the health effects of exposure to erionite: a four-year study in the Cappadocian region of Turkey.Int J Cancer. 1987; 39: 10-17Crossref PubMed Scopus (211) Google Scholar, 5Saracci R Simonato S Baris Y et al.The age-curve of endemic pleural mesothelioma in Karain, Central Turkey.Br J Cancer. 1982; 45: 147-149Crossref PubMed Scopus (13) Google Scholar we could only rely on the direct diagnostic investigations done with Baris and his team rather than on seldom existent medical records. The conjecturing of a genetic component in the causation of some mesotheliomas is one thing; to show its actual role is another, requiring much more information than reported. This evidence is essential scientifically and for the wider public-health implications, given the weight that a genetic factor may carry when debating liability in asbestos-related mesotheliomas. Familial malignant mesotheliomaAuthor's reply Full-Text PDF