Occupational exposure to vinyl chloride and risk of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a common form of cancer that arises from hepatocytes and whose risk may be affected by several known factors, including viruses, alcohol, cigarette smoking, and several genetic conditions. Liver angiosarcoma is a rare cancer that develops from endothelial cells and whose most relevant known risk factor is occupational exposure to vinyl chloride (VC). Since occupational exposure to high levels of VC may still occur, we reviewed the epidemiological and experimental evidence supporting the notion that inhalation exposure to VC is a risk factor for HCC. We find that available epidemiological evidence is based on a dose-risk study with 10 HCC cases and on a partially overlapping study reporting similar results: neither study provided controls for known non-occupational confounders for HCC. Carcinogenesis bioassays of VC inhalation in rodents indicate that angiosarcomas account for nearly all liver tumors induced. Thus, the role of inhalation exposure to VC in HCC risk remains unclear, awaiting further studies and the integration of results from epidemiological studies and animal models.

Hepatocellular carcinoma and the risk of occupational exposure

“…induce specific gene mutations in the liver [105][106][107][108][109][110][111][112][113][114][115][116][117] . Various European and Italian studies have reported the apparent association between the amount and timing of exposure to VCM and development of HCC in those exposed [118][119][120] .…”

Vinyl chloride industry in the courtroom and corporate influences on the scientific literature

“…The trial elicited original studies from consultants to the public prosecutors, who provided part of the available evidence on the association between VC and HCC [Pirastu et al, 2003;Mastrangelo et al, 2004]; additional studies from independent researchers were consistent with this finding, which was confirmed by the last IARC assessment. Consultants of the VC industry issued 4 reviews of epidemiological studies (out of 6 published in English language since the beginning of the trial) [McLaughlin and Lipworth, 1999;Bosetti et al, 2003;Dragani and Zocchetti, 2008;Sherman, 2009]. The first reviews amplified doubts and limitations in the available literature, and supported the judges' decision on the presence of uncertainties about the association between VC and HCC.…”

Vinyl Institute Comments on Cicalese et al.: “An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas”

“…No available risk assessment suggests that an ambient level of VCM of 0.01 µg/m 3 presents a risk of harm based on exposures over an average lifetime. In humans, the level of exposure to VCM must be > 7,531 ppm-years to develop ASL [4] 1 . Available information suggests that exposure to VCM must be 10-fold higher to develop HCC, far exceeding actual exposures.…”

“…Available information suggests that exposure to VCM must be 10-fold higher to develop HCC, far exceeding actual exposures. The evidence of risk of HCC from VCM exposure is based on a few and overlapping data [4-6] 2, 3 .…”