Causes of death among lead smelters in relation to the glucose-6-phosphate dehydrogenase polymorphism

Objective. To assess adverse health effects following occupational lead exposure in relation to the glucose-6-phosphate dehydrogenase (G6PD) polymorphism, we updated a follow-up mortality study of a lead smelters cohort in Sardinia, Italy. Method. We followed up the 1973-2003 mortality in 1,017 male lead smelters, divided into two subcohorts according to the G6PD phenotype, whether G6PD deficient (G6PD-) or wild type (wtG6PD). Observed deaths in the overall cohort and the two subcohorts were compared to the expected, based on the age-, sex- and calendar year-specific mortality rates in the general male population of the island. Directly standardized mortality rates in the two subcohorts were also compared. Results. Among production and maintenance workers, cardiovascular mortality was strongly reduced, most likely related to the healthy worker effect. However, the standardized mortality rate for cardiovascular diseases was substantially lower among the G6PD- subcohort (5.0 x 10-4) compared wtG6PD subcohort (33.6 x 10-4; ƒO p NS). Neoplasms of the haemopoietic system exceeded the expectation in the G6PD- subcohort (SMR = 388; 95% C.I. 111-1108). No other cancer sites showed any excess in the overall cohort or in the two subcohorts. No death from haemolytic anemia occurred in the G6PD- subcohort. Conclusion. With due consideration of the limited statistical power of our study, we confirm previous results suggesting that, in workplaces where exposure is under careful control, expressing the G6PD- phenotype does not convey increased susceptibility to lead toxicity. The observed excess risk of haematopoietic malignancies seems to have most likely resulted from chance.