Incidence of cancer among workers exposed to vinyl chloride in polyvinyl chloride manufacture

Based on results from two previous studies where an excess of melanomas was found in a cohort of workers exposed to vinyl chloride (VCM), a follow up of the incidence of cancer in the same cohort of 428 workers was carried out to scrutinise whether or not the excess could be confirmed by new cases. The total number of deaths in the study group from 1953 to the end of 1993 was 132 v 141 expected, and the total number of incident cancer cases was 56 v 57 expected. There were 11 cases of lung cancer v eight expected, seven cases of melanomas v 2.07 expected, and two cases of thyroid cancer v 0.34 expected. Five of the seven melanoma cases had occurred in the group that had been most heavily exposed to VCM v 0.7 expected. In the present follow up we also found five cases of the spinocellular cancer of the skin v 1.7 expected. Out of these five cases four were diagnosed after 1984. Two of the five cases v 0.7 expected had occurred in the most heavily exposed group. The total number of skin cancers (melanomas and spinocellular cancers) were 12 v 3.7 expected. There was one new case of melanoma between 1985 and 1993 v 0.7 expected. Hence, the strength of the relation between the observed and expected number of cases was reduced compared with the last follow up, and does not strengthen the previously indicated causal relation between exposure to VCM and development of malignant melanoma. There was no excess of testicular cancers in this study. The present results may indicate that occurrence of spinocellular skin cancer could bear some relation to work in the manufacture of polyvinyl chloride (PVC). Confirmation is needed from studies on other cohorts exposed to VCM.


Keywords: cohort study; aetiology; exposure; melanomas; spinocellular cancers     

An industry-wide epidemiologic study of vinyl chloride workers, 1942-1982

The cohort consisted of 10,173 men who had worked for at least one year in jobs involving exposure to vinyl chloride prior to 1 January 1973. These men were employed at 37 plants in the U.S., belonging to 17 companies. Observation of the mortality experience of the cohort was updated from 31 December 1972 to 31 December 1982 (the study now covering 1942-1982). A total of 1,536 cohort members were identified as having died. The observed mortality, by cause, was compared with the expected based on U.S. mortality rates, standardized for age, race, and calendar time. Analyses by length of exposure, latency, age at first exposure, calendar year of first exposure, and type of products were performed. The study confirmed that the vinyl chloride workers experience a significant mortality excesses in angiosarcoma (15 deaths), cancer of the liver and biliary tract (SMR = 641), and cancer of the brain and other central nervous system (SMR = 180). In addition, the study also found a significant mortality excess in emphysema/chronic obstructive pulmonary disease (COPD) (SMR = 179). On the other hand, the study did not find any excess in either respiratory cancer or lymphatic and hematopoietic cancer. This study also found an increase in biliary tract cancers, independent from liver cancer.     

Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80-3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.     

A collaborative study of cancer incidence and mortality among vinyl chloride workers

A large European multicentric cohort study has been coordinated by the International Agency for Research on Cancer with the objectives of investigating the dose-response relationship between liver cancer and exposure to vinyl chloride and assessing cancer risk for sites other than the liver. A nearly threefold increase in liver cancer was detected on the basis of 24 observed deaths and 8.4 expected (standardized mortality ratio 286, 95% confidence interval 186-425). The excess from liver cancer was clearly related to time since first exposure, duration of employment, and estimated ranked and quantitative exposures. Other cancer sites investigated on the basis of a priori hypotheses were either not in excess (lung) or apparently unrelated to the exposure variables (brain and lymphoma).     

Asbestos exposure, smoking habits, and cancer incidence among production and maintenance workers in an electrochemical plant

The incidence of cancer was studied in a cohort of 287 men who were exposed to asbestos at a nitric acid production plant from 1928 onwards. During the observation period from 1953 through 1980 all cancer cases among the cohort members were identified in The Cancer Registry. For the whole cohort 42 cases of cancer were observed versus 30.6 expected. The figures for cancer of the lungs and pleura combined were 17 observed versus 3.7 expected. The corresponding figures for a heavily exposed subcohort were 11 observed and 1.2 expected. In that group there was also an increased incidence of colon cancer with 3 cases observed against 0.8 cases expected. Within the whole cohort four cases of pleural and one case of peritoneal malignant mesothelioma were found. There was also an increased incidence of malignant melanoma of the skin with 3 cases observed against 0.6 expected. For cancer cases that were registered as of unknown origin there were 7 cases observed and 1.4 expected. There was no increased rate ratio for cancer at any site before 20 years after the first asbestos exposure. The smoking habits of all cohort members were recorded and the relative rates for lung cancer were calculated in relation to smoking habits. In common with previous studies the results indicate a multiplicative model for the interaction between asbestos exposure and smoking in regard to lung cancer risk.     

Liver and biliary tract cancer among chemical workers

A recent cohort mortality study of male, hourly wage employees of a large Michigan chemical production and research facility had found a greater than expected number of deaths coded to liver and biliary tract cancer. In response, an additional investigation was then undertaken of the 44 liver and biliary tract cancer deaths observed between 1940 and 1982. A random sample (N = 1,888) of subjects was selected from the total cohort (N = 21,437) to serve as referents. Company work history records were used to classify cases and referents by work area assignment and potential for exposure to 11 selected chemical agents which have been shown to produce cancer of the liver or biliary passages in experimental animals. Statistically significant associations in both positive and negative directions were found for several work areas within the facility. A suggestive association was found for vinyl chloride monomer, based on five cases with presumed exposure.     

Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant

To study whether exposure to low levels of vinyl chloride monomer (VCM) causes increased risk for cancer morbidity and death from ischemic heart disease, a cohort study was performed among 2,031 male workers at a polyvinyl chloride (PVC) processing plant who had been employed for at least 3 months during the period 1945-1980. An almost significantly increased total mortality (SMR = 116, 95% CI 99-136) was found. Deaths caused by violence or intoxication were significantly increased (SMR = 153, 95% CI 109-213), but not deaths from ischemic heart disease (SMR = 100, 95% CI 73-135). A significant increase in total cancer morbidity was observed (SMR = 128, 95% CI 101-161). Respiratory cancers were significantly increased (SMR = 213, 95% CI 127-346). Furthermore, six brain tumors (vs. 2.6 expected) were observed. This increase, however, was not significant (SMR = 229, 95% CI 84-498). No liver hemangiosarcoma was observed. Applying a latency period of greater than or equal to 10 years from start of employment did not change the risk patterns. There were no significant exposure-response associations between exposure estimates for VCM, asbestos, and plasticizers and cancer morbidity.     

氯乙烯作业工人恶性肿瘤流行病学调查研究

目的 为了解氯乙烯作业工人恶性肿瘤发病情况。方法 采用回顾前瞻性观察法,对921名氯乙烯作业工人进行了40年死因流行病学调查。结果 男性接触组肝癌死亡率明显高于对照组。RR为2．16（P＜0．05）;接触组恶性肿瘤、肝癌的死亡也显著高于1994年全国城市居民恶性肿瘤的死亡率及1995年全国城市居民肝癌的死亡水平。SMR分别为1．8、29（P＜0．05）。在恶性肿瘤分类构成中,接触组肝癌居首位。结论 氯乙烯作业工人肝癌高发具有职业性特征。     

An epidemiological study of workers exposed to vinyl chloride in the plants of Ferrara, Rosignano and Ravenna

The aim of the present study is to investigate cause-specific mortality among male workers employed in vinyl chloride manufacture and polymerization in three Italian plants located in Ferrara, Rosignano and Ravenna. The cohorts include all workers hired between start of operation and, respectively 1985, 1978 and 1985, amounting to 418, 206 and 635 subjects followed up for mortality until 1996 (Ferrara and Rosignano) and 1997 (Ravenna). Cause specific SMRs (Standardized mortality ratios) were computed. Expected figures were obtained from mortality rates for the population resident in the region where the plant was located, for each SMR value a 90% confidence interval (CI) was calculated on the assumption of a Poisson distribution. The study detected an increased mortality for primary liver cancer in all three plants; SMR values were 444 in Ferrara (4 Obs. 90% CI 160-1069), 200 in Rosignano (1 Obs. 90% CI 10-869) and 375 in Ravenna (3 Obs. 90% CI 110-1038). In the pooled cohort liver cancer SMR was equal to 364 (8 Obs. 90% CI 108-390). In one plant, Ferrara, observed mortality was above the expected for lung cancer, SMR = 146 (14 Obs. 90% CI 89-229) and for larynx cancer, SMR = 500 (4 Obs. 90% CI 174-1167). One death from pleural cancer was observed in Rosignano (SMR = 1000 90% CI 47-4331). A non significant increase was detected for liver cirrhosis, in Ferrara (SMR 108, 6 Obs. 90% CI 73-332) and Rosignano (SMR 129, 3 Obs. 90% CI 35-332). The study results are confirming the carcinogenic action of vinyl chloride on the liver, they are pointing to its possible role in lung cancer development, as already shown for workers employed in Porto Marghera; an increased risk for larynx cancer is also shown.     

Angiosarcoma of the liver in Great Britain in proximity to vinyl chloride sites.

OBJECTIVES: To study the incidence of angiosarcoma of the liver in England and Wales 1979-86 and Scotland 1975-87. To investigate whether any non-occupational neighbourhood cases occurred near a vinyl chloride site. METHODS: This is a geographical study of incident cases among the general population of Great Britain. Diagnosis of angiosarcoma of the liver was based mainly on the national cancer registry, the world register of cases among vinyl chloride workers, and the register of cases (including histological review) maintained by the Health and Safety Executive. Proximity (< 10 km) of residence to a vinyl chloride site was based on postcode of address at the time of diagnosis. RESULTS: 55 cases were ascribed to angiosarcoma of the liver in England and Wales with a further six cases in Scotland (annual incidence in Great Britain from all sources of around 1.4 cases per 10 million population). There were two cases with documented exposure to Thorotrast, and 10 cases among vinyl chloride workers. There were no vinyl chloride sites in Scotland. Among the 25 cases in England and Wales with histological diagnosis after review by a panel of pathologists, only 15 were confirmed as angiosarcoma, and one of the two Scottish cases after histological review was also confirmed. Overall, 11 cases ascribed to angiosarcoma were resident within 10 km of a vinyl chloride site; nine were vinyl chloride workers, one further case on histological review was not considered to have been correctly diagnosed as angiosarcoma, and the remaining case, confirmed as angiosarcoma, was employed at a vinyl chloride factory during the late 1950s, although not as a vinyl chloride worker. CONCLUSION: The incidence of angiosarcoma of the liver in Great Britain remains extremely rare. The one confirmed case in a non-vinyl chloride worker within 10 km of a site must nevertheless be presumed to have been exposed to vinyl chloride in the workplace. In the period of study, there were no confirmed non-occupationally exposed cases of angiosarcoma among residents living near a vinyl chloride site in Great Britain.     

Vinyl chloride exposure in a controlled industrial environment. A long-term mortality experience in 594 employees.

Vinyl chloride has been associated recently with findings of angiosarcoma in animals and man. The present study examines the mortality experience of individuals occupationally exposed to vinyl chloride and lesser amounts of vinylidene chloride and other compounds. Employees were grouped into four exposure categories according to the highest levels of vinyl chloride exposure experienced for at least one month. Although no angiosarcomas were found and there were no deaths due to any liver malignancy, the observed malignancy deaths exceeded the expected among workers in the high-exposure category. Fewer than expected malignancy deaths were observed in the remaining exposure catergories.     

Epidemiologic study of workers exposed to vinyl chloride in Porto Marghera: mortality update

The investigation describes mortality of vinyl chloride exposed workers in the Montedison-Enichem plant located in Porto Marghera, near Venice, Italy. A total of 1658 workers employed from start of production (1950), present in 1956 or successively hired until 1985, were followed up between 01.01.1973 and 31.07.1999, for a total of 41.037 person years at risk: 248 deaths were observed. Mortality from all causes compared with regional population was lower than expected, (SMR 0.75; 90% CI 0.68-0.83) and from all malignant neoplasms similar to expected (SMR 0.94; 90% CI 0.81-1.09). SMR for primary liver cancer was significantly increased (SMR 2.78 90% CI 1.86-4.14). In the first year since leaving employment observed mortality was significantly above the null value for all causes (SMR 2.76; 90% CI 1.94-3.91), all malignant neoplasms (SMR 1.89; 90% CI 0.97-3.92) and cardiovascular diseases (SMR 2.37; 90% CI 1.13-4.95). Mortality rates for liver angiosarcoma (6 cases) increased with latency (trend test x 2 (1df) = 25.20 p < 0.001) and cumulative exposure (trend test x 2 (1df) = 61.00 p < 0.001), there were no cases with duration of employment less than 12 years, latency less than 10 years and for cumulative exposure less than 2.379 ppm-years. Mortality rates for hepatocellular carcinoma (12 cases) and liver cirrhosis (20 cases) showed a similar pattern for cumulative exposure. Observed mortality from lung cancer was higher than expected among those workers whose only job title was bagger. In the analysis accounting for latency, age and calendar period the RR for only bagger was 2.31 (90% CI 1.15-4.61). Mortality pattern for all causes, all malignancies and cardiovascular disease increased by time since employment, as expected in presence of a particularly strong Healthy Worker Effect (HWE). These results and the increased SMR values during the first year since leaving employment indicate that workers were selected into employment on the basis of good health conditions and early selective removal of weaker ones followed. The study results confirm the causal relationship between VCM exposure and liver angiosarcoma, and add supplementary evidence in favour of a causal explanation of the excess risk for hepatocellular carcinoma and liver cirrhosis as well as lung cancer among only baggers.     

Incidence of cancer in a cohort of magnesium production workers

The results from a cohort study on the incidence of cancer and the mortality in a cohort of 2391 male workers producing magnesium metal are presented. The study population was restricted to employees with more than one year of work experience in the study plant between 1951 and 1974 and the cohort was observed from 1953 to 1984. Altogether 152 new cases of cancer were observed versus 132.6 expected. Six cases of cancer of the lip were found against 2.3 expected, 21 of stomach cancer against 12.8 expected, and 32 of lung cancer against 18.2 expected. A possible causal relation between exposure to factors in the work environment and the development of cancer is discussed.     

Incidence of cancer in a cohort of magnesium production workers.

The results from a cohort study on the incidence of cancer and the mortality in a cohort of 2391 male workers producing magnesium metal are presented. The study population was restricted to employees with more than one year of work experience in the study plant between 1951 and 1974 and the cohort was observed from 1953 to 1984. Altogether 152 new cases of cancer were observed versus 132.6 expected. Six cases of cancer of the lip were found against 2.3 expected, 21 of stomach cancer against 12.8 expected, and 32 of lung cancer against 18.2 expected. A possible causal relation between exposure to factors in the work environment and the development of cancer is discussed.     

Incidence of cancer among welders and other workers in a Norwegian shipyard

The incidence of cancer among 4778 male shipyard workers, including 783 mild steel welders, was investigated in a historical cohort study. The workers had been employed for at least three months between 1 January 1946 and 31 March 1977. The incidence of cancer was observed from 1 January 1953 through 1986. The loss during follow-up was only 0.9%. There were 53 observed cases of lung cancer in the whole cohort versus 31.3 expected on the basis of the national rates for men. There was an increased incidence of lung cancer among the welders, with seven observed cases versus 3.2 expected. Twenty-two cases of bladder cancer were observed versus 15.2 expected. Two malignant mesotheliomas had occurred (0.7 expected). Smoking was likely to be a confounder in the present study. Due to concomitant exposure to asbestos, the results are inconclusive concerning the possible relationship between exposure to welding fumes and lung cancer.     

Lung cancer risk in workers exposed to poly(vinyl chloride) dust: a nested case-referent study

Background: There have been few investigations of an association between poly(vinyl chloride) (PVC) dust exposure and an increase in lung cancer incidence, and their conclusions have been inconsistent.

Aims: To determine whether PVC and/or vinyl chloride monomer (VCM) is the associated risk factor(s), by means of a nested case-referent study, in order to estimate lung cancer risk, avoiding selection, information, or confounding biases.

Methods: Thirty eight cases of histologically verified lung cancer and 224 control subjects without a history of cancer were selected from an Italian cohort of 1658 vinyl chloride workers. Information sources included clinical records (diagnosis, smoking habits) and plant records (occupational history). The risk of lung cancer was estimated by odds ratios (OR) with 95% confidence intervals (CI), calculated using logistic regression models.

Results: In PVC baggers exposed to high levels of respirable PVC particles in the workplace, the lung cancer OR increases by 20% for each extra year of work (OR = 1.2003; 95% CI 1.0772 to 1.3469; p = 0.0010), when the influence of age and smoking habits is controlled. No relation was found between lung cancer and cumulative VCM exposure.

Conclusion: This nested case-control study showed, in the VCM/PVC industry, an increased risk of lung cancer associated with exposure to PVC dust; previous cohort studies failed to recognise such excess, probably because they used VCM exposure as the risk indicator.

     

Exposure to vinyl chloride monomer: report on a cohort study

In 1980 a prospective exposed/non-exposed cohort study was initiated in France by the Institut National de la Santé et de la Recherche Médicale (INSERM U 287) to evaluate the association between mortality and cancer morbidity and occupational exposure to vinyl chloride monomer (VCM). Eleven hundred VCM exposed subjects and 1100 VCM non-exposed controls matched for age (+/- 2 years), plant, and physician were included and followed up over a five year period for vital, health, and occupational status. The percentages of deaths observed among the exposed (1.8%) and non-exposed subjects (1.6%) did not differ. Eighteen (1.6%) and 15 (1.4%) cases of cancer were reported among exposed and non-exposed subjects, respectively (NS). One case of angiosarcoma of the liver occurred among the exposed group; six cases of lung cancer occurred among exposed subjects and two among non-exposed subjects (NS). The percentage of diseases of the circulatory system was higher (p less than 0.02) in the exposed group than in the non-exposed group: this difference was explained mainly by the high incidence of Raynaud's disease (p less than 0.006). The percentages of diseases of the respiratory system did not differ between the two groups.     

氯乙烯作业工人恶性肿瘤发病情况的前瞻性流行病学调查

对全国范围内12个城市的13个大、中型聚氯乙烯生产工厂5 291名接触氯乙烯的工人,及6 276名对照工人,进行了从1982-01-01～1989-12-31为止的前瞻性流行病学调查。结果没有发现肝血管肉瘤患者,但接触组男工肝癌的死亡率显著高于我国中等城市男性居民肝癌的死亡率(P<0.05),在恶性肿瘤的分类构成中,接触组男工以肝癌居首位,而且肝癌的发病年龄比对照组显著提前。     

Exposure to vinyl chloride monomer: report on a cohort study.

In 1980 a prospective exposed/non-exposed cohort study was initiated in France by the Institut National de la Santé et de la Recherche Médicale (INSERM U 287) to evaluate the association between mortality and cancer morbidity and occupational exposure to vinyl chloride monomer (VCM). Eleven hundred VCM exposed subjects and 1100 VCM non-exposed controls matched for age (+/- 2 years), plant, and physician were included and followed up over a five year period for vital, health, and occupational status. The percentages of deaths observed among the exposed (1.8%) and non-exposed subjects (1.6%) did not differ. Eighteen (1.6%) and 15 (1.4%) cases of cancer were reported among exposed and non-exposed subjects, respectively (NS). One case of angiosarcoma of the liver occurred among the exposed group; six cases of lung cancer occurred among exposed subjects and two among non-exposed subjects (NS). The percentage of diseases of the circulatory system was higher (p less than 0.02) in the exposed group than in the non-exposed group: this difference was explained mainly by the high incidence of Raynaud's disease (p less than 0.006). The percentages of diseases of the respiratory system did not differ between the two groups.     

氯乙烯作业工人恶性肿瘤发病情况的流行病学调查

对全国12个城市的13个聚氯乙烯制造工人中5459名氯乙烯作业工人和6461名对照厂工人进行了从投产到1989年12月31日为止的恶性肿瘤发病情况的回顾性和前瞻性队列调查。结果表明,男工接触组肝癌的发病率、死亡率均显著高于对照组,男性肝癌的死亡率也显著高于我国中等城市男性肝癌的死亡率。在恶性肿瘤的分类构成中,接触组男工的肝癌居首位。接触组男工肝癌的发病年龄比对照组显著提前。