CORRESPONDENCE

Re: Trends in U.S. Pleural Mesothelioma Incidence Rates Following Simian Virus 40 Contamination of Early Poliovirus Vaccines

Riccardo Puntoni, Monica Neri, Paolo G. Cerrano, Rosangela Filiberti

Affiliation of authors: R. Puntoni, M. Neri, P. G. Cerrano, R. Filiberti, Environmental Epidemiology and Biostatistics, National Cancer Research Institute of Genoa, Genoa, Italy.

Correspondence to: Riccardo Puntoni, Ph.D., Environmental Epidemiology and Biostatistics, National Cancer Research Institute of Genoa, Largo Rosanna Benzi, 10, 16132 Genoa, Italy (e-mail: riccardo.puntoni{at}istge.it).

In a recent article in the Journal, Strickler et al. (1) estimated age- and sex-specific pleural mesothelioma incidence rates from 1975 through 1997. These trends were then compared with trends in prevalence of exposure to simian virus 40 (SV40)-contaminated poliovirus vaccine. The authors concluded that "Age-specific trends in U.S. pleural mesothelioma incidence rates are not consistent with an effect of exposure to SV40-contaminated poliovirus vaccine." In our opinion, the observed plateau in pleural mesothelioma incidence after 1992 is not in conflict with a possible effect of SV40 for three reasons. First, because pleural mesothelioma is a disease of the elderly, even an increasing incidence among the youngest individuals would lead to a number of cases too small to modify the general trend. The exposure prevalence by age may be better evaluated by disaggregating the data into age groups (Table 1Go). Among individuals in the 25- to 44-year age groups, half the cohort (i.e., those aged 25–34 years) includes few exposed people in the last two periods of observation (i.e., 1991–1994 and 1995–1997). Moreover, in this group, few cases are able to modify the age-specific trend. For this reason, the 3-year period, 1995–1997, should be excluded from the analysis. Among those in the 45- to 54-year age group, trends show a decrease among males and a slight increase among females [Fig. 2, B in (1)]. In the oldest age groups, the prevalence of SV40 exposure increases over time, as does the trend of pleural mesothelioma incidence. Second, it is important to consider the latency period of pleural mesothelioma. In occupational studies of long-term asbestos exposure, time since first exposure ranges from 10 to 60 or more years (2,3). Epidemiologic data suggest that the latency period for pleural mesothelioma is longer than 40 years, particularly if an individual inhaled asbestos at a very young age. The latency period may be different in the case of a viral contamination; however, in such a case, a similarly long-term presence of SV40 in the body compartments can be hypothesized. Among young individuals inoculated with SV40-contaminated vaccine, the virus could remain silent for many years and then possibly interact with asbestos that remains in the pleura as well. Indeed, SV40 is able to initiate oncogenic transformation of cells. The large T antigen of SV40 inactivates the p53 and Rb tumor suppressor genes and promotes immortalization of cells (46). However, additional cellular changes are necessary for a tumor to develop. The timing of these events could occur slowly, inducing mesothelioma even 60 years after the first exposure. Third, the Institute of Medicine recently concluded that epidemiology that is based on the differences between exposed and non-exposed cohorts is of dubious significance because it is impossible to clearly separate these two cohorts (7). Recent data [reviewed in (5)] suggest that SV40 may have contaminated some vaccines even after 1963, and/or that human-to-human transmission of SV40 may occur.


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Table 1. Rough estimates of the prevalence of exposure to SV40-contaminated poliovirus vaccine by age at exposure and year of birth in different age groups*
 
Regardless of the route of infection, the molecular pathologic evidence indicates that SV40 is a factor in the pathogenesis of some mesotheliomas (5,6). We believe, however, that the epidemiologic data currently available are insufficient to draw definitive conclusions about the possible contribution of SV40-contaminated poliovaccines to the overall increase in the incidence of mesothelioma in the past 40 years.

REFERENCES

1 Strickler HD, Goedert JJ, Devesa SS, Lahey J, Fraumeni JF Jr, Rosenberg PS. Trends in U.S. pleural mesothelioma incidence rates following simian virus 40 contamination of early poliovirus vaccines. J Natl Cancer Inst 2003;95:38–45.[Abstract/Free Full Text]

2 Puntoni R, Merlo F, Borsa L, Reggiardo G, Garrone E, Ceppi M. A historical cohort mortality study among shipyard workers in Genova, Italy. Am J Ind Med 2001;40:363–70.[CrossRef][Medline]

3 Bianchi C, Giarelli L, Grandi G, Brollo A, Ramani L, Zuch C. Latency periods in asbestos-related mesothelioma of the pleura. Eur J Cancer Prev 1997;6:162–6.[Medline]

4 Butel JS, Lednicky JA. Cell and molecular biology of simian virus 40: implications for human infection and disease. J Natl Cancer Inst 1999;91:119–34.[CrossRef][Medline]

5 Gazdar, A, Butel, JS, Carbone M. SV40 and human tumours: myth, association, or causality? Nat Rev Cancer 2002;2:957–64.[CrossRef][Medline]

6 Carbone M, Kratzke RA, Testa JR. The pathogenesis of mesothelioma. Semin Oncol 2002;29:2–17.

7 Stratton K, Almario DA, McCormick MC. SV40 contamination of poliovaccine and cancer. Immunization Safety Review Committee, Institute of Medicine, National Academy of Sciences. Washington (DC): The National Academy Press; 2002. p. 1–76. Available at: http://www.nap.edu. [Last accessed: 03/07/2003.]



             
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