High incidence of renal tumours in vitamins A and E synthesis workers: A new cause of occupational cancer?

Abstract

Dear Sir,Renal cell carcinoma (RCC) is the most common adult kidney tumour, accounting for around 3% of human malignancies. 1 Its incidence is about 11/100,000 person-years in industrial countries and is increasing as the result of both increases in the prevalence of risk factors and in use of diagnostic imaging procedures. 2-3 Main histological subtypes include clear-cell (75%), papillary (10%) and chromophobe (5%) RCC. Complete surgical resection is considered to be curative for localised RCC but 30% of patients have metastatic disease at diagnosis and RCC is responsible for about 95,000 deaths per year world-wide. 1 Little is known regarding etiological factors of RCC. 2,4 Familial RCC syndromes are estimated at less than 5%; the 2 main conditions are von Hippel-Lindau disease, related to the tumour-suppressor VHL gene, for clear-cell RCC; and hereditary papillary RCC, caused by the c-MET proto-oncogene. 5 Most cases of RCC are thought to be sporadic and many factors are known to increase the risk. Tobacco smoking, obesity (particularly among women), high blood pressure and/or medication prescribed to treat this condition are the main established, although modest, risk factors. 6 -8 A number of reports have also pointed out the potential nephrocarcinogenic effect of occupational exposure to trichloroethylene, gasoline, petroleum products, asbestos, cadmium and iron processing fumes; corresponding epidemiological studies, however, are sometimes controversial. 9 -12 Somatic inactivation of the VHL gene is found in up to 70% of sporadic clear-cell RCC whereas somatic c-MET mutations only occur in 13% of papillary tumours. [13][14][15][16] Prolonged exposure to trichloroethylene during metal machining is associated with clear-cell RCC harbouring a specific pattern of VHL somatic mutations; the identification of this putative mechanism increases the probability for a causative role of trichloroethylene in RCC. 12,17 We recently were made aware of an unexpected number of RCC occurring in a French factory that specialised in vitamin A, vitamin E and methionine synthesis. Between March 1994 and October 2002, 10 cases of RCC were detected in workers from this factory that currently employs 612 men and 116 women. Because of the use of vinyl chloride, a well-documented liver carcinogen, an annual abdominal ultrasonography was progressively introduced in worker medical surveillance in the end of the 1980s. The first RCC was detected by chance in 1994 in a 48-year-old man, who had worked at vitamin A synthesis from 1979 to 1988. To date, 9 further men with RCC have been discovered through systematic ultrasonography and confirmed by CT-scan [ Table I]. Mean age at diagnosis was 52.3 Ϯ 7.8 years and mean diameter of tumour was 2.9 Ϯ 1.0 cm. All patients were successfully operated upon (6 patients underwent a nephrectomy and 4 were treated by conservative surgery) and were free of disease in March 2003. Review of tumour slides identified 7 clear-cell and 3 papillary RCC. The renal tumour was unique in 9 patients and multifoc...

Chemistry and biology of vitamin E

“…The reduction in the number of large primary mammary tumors and lung metastases was attributed to the increase in reactive oxygen species (caused by the lack of vitamin E) and subsequent apoptosis [174]. A very recent report describes the unexplained increase of 13 times of the standardized incidence ratio for renal cell carcinoma in workers in a vitamin A and E synthesis plant in France [175]. However, more workers in vitamin A than in vitamin E production were affected, and tumor development may be due to occupational exposure to any of the chemicals used in synthesis (more than 60), although none of these had previously been related to renal cell carcinoma [175].…”

An extensive epidemiological investigation of a kidney cancer cluster in a chemical plant: what have we learned?

“…The estimated SIR of 13.1 confirmed an excess of kidney cancers 1. Nonetheless, this could partially be explained by the early diagnosis due to the abdominal ultrasound screening.…”

“…Diagnosis of the 10 index cases had histologically been confirmed 1. Among the 12 additional cases, diagnosis was based on death certificate in three cases, Computed tomography (CT) results in one case and histological confirmation for the remaining seven cases.…”

“…In 2003, the plant employed about 700 workers. Ten cases of kidney cancer had been reported, all involving renal cell carcinoma (RCC), including seven clear-cell and three papillary cases 1. They had been diagnosed in men who had been employed at the plant between 1994 and 2002.…”

Screenings and clusters: a cancer cluster in a chemical plant

“…Screening identified RCC in 10 male plant workers during 1994 through 2002 2. Nine of the men synthesised vitamin A.…”