SV40 and Asbestos Exposure Increase Malignant Mesothelioma Risk

Written by Joyce Smith, BS. Study shows a significant association between malignant mesothelioma and those who were exposed to asbestos and positive for SV40 virus.

While asbestos is the major cause of malignant mesotheliomas, only a small percentage of individuals exposed to asbestos during their lifetime will actually develop the disease (1). This suggests a contributory role for other carcinogenic agents. The Simian SV40 virus may be one of these. Between 1958 and 1963 nearly 100 million Americans received polio vaccinations of which an estimated 10 – 30 million doses were contaminated with SV40 (2). This became a major concern when studies actually found SV40 present in many individuals who had been diagnosed with mesothelioma. The SV40 virus interacts with cellular DNA to suppress the synthesis of tumor-suppressing p53 protein which is responsible for cell death (apoptosis). Thus the cell becomes transformed into a tumor cell. Promotion of telomerase activity extends the length of the telomers (tip of chromosome) to further support cell immortalization and delaying cell death (4).

One such study led by Dr. Carbone found that 54% of all malignant mesothelioma (MM) patients had SV40 in their malignant mesothelial cells, yet he found no evidence of SV40 virus in other types of lung cancer (5). A more recent 2008 study demonstrated that injecting the pleural cavities of hamsters with SV40 caused 60% of them to die of mesothelioma (6). These studies validated concerns regarding possible link between SV40 and asbestos induced cancer, but there was no conclusive evidence that linked SV40 alone to mesothelioma.

The question for the researchers became “Does the presence of SV40 in MM and bladder urothelioma tumors increase the risk of developing MM in individuals exposed to asbestos?

They hypothesized that SV40 contributes to the development of mesothelioma only as a co-factor rather than the direct cause. To test this hypothesis they chose a molecular epidemiologic case-control study to determine if people exposed to asbestos and infected with SV40 virus have an increased risk of developing MM.

The study consisted of 19 patients diagnosed with MM and 18 control patients diagnosed with bladder urotheliomas. Urotheliomas were chosen for controls because there was no data in the medical literature that indicated a link to either SV40 or asbestos. The recruitment of both the MM patients and the controls was on a random basis and the tumors from both were examined histologically and classified. A personal history of previous asbestos exposure was also obtained. Tumor samples were then tested for the presence of SV40 virus and odds ratios (OR) and 95% confidence intervals (95%CI) for the association between MM and SV40 or asbestos were calculated.

Results:

• There was a statistically significant association between MM and a personal history of previous exposure to asbestos (OR, 7.6; 95% CI, 1.7 – 33.1) P=0.007
• There was also a significant association between MM and presence of both asbestos and SV40 when the combined effect of both SV40 and asbestos was analyzed. (OR, 12.6 (95% CI, 1.2 – 133.9) P=0.035.

This indicates that patients who were exposed to asbestos and were also positive for SV40 had a 12.6-fold higher risk of MM than subjects with no previous asbestos exposure and no SV40 DNA.

• In mesothelioma patients who had no exposure to SV40, the strength of the association with asbestos was much weaker.

• The Researchers concluded that SV40 alone may not be able to cause MM in humans; however, it functions as a cofactor that strongly increases the carcinogenic effect of asbestos exposure. More importantly, the researchers believe that “detection of SV40 among a cohort of individuals exposed to asbestos could be a useful marker to identify those at higher risk for MM. This subgroup of high risk individuals could be closely monitored for early detection and possibly curative surgical excision. It follows that since SV40 increases the risk of MM among individuals exposed to asbestos, searching for ways to better diagnose and identify these high-risk individuals is critical to saving more lives.

Source: Cristaudo, Alfonso, et al. “SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study.” Cancer research 65.8 (2005): 3049-3052.

© 2005 American Association for Cancer Research.

Posted July 28, 2015.

References:

1. Rizzo P, Bocchetta M, Power A, et al. SV40 and the pathogenesis of MM. Semin Cancer Biol 2001; 11: 63–71. CrossRefMedline
2. Stratton K, Almario DA, McCormick M, editors. Institute of Medicine report 2002. Immunization safety review: SV40 contamination of polio vaccine and cancer. Washington, DC: The National Academy of Sciences; 2002. Available from: http://www.nap.edu.
3. De Luca A, Baldi A, Esposito V, et al. The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human MMs. Nature 1997; 3: 913–6. CrossRefMedline
4. Foddis R, De Rienzo A, Broccoli D, et al. SV40 infection induces telomerase activity in human MM cells. Oncogene 2002; 21: 1434–42. CrossRefMedline
5. Carbone M, Pass HI, Rizzo P, et al. Simian virus 40-like DNA sequences in human pleural MM. Oncogene 1994; 9: 1781–90. Medline
6. Riviera et al, The Relationship between Simian Virus and Mesothelioma.” Curr Opin Pulm Med. 2008 Jul;14(4):316-21. doi: 10.1097/MCP.0b013e3283018220. Review.