Mortality risk among workers with exposure to dioxins.

BACKGROUND: In several studies, dioxin exposure has been associated with increased risk from several causes of death. AIMS: To compare the mortality experience of workers exposed to dioxins during trichlorophenol (TCP) and pentachlorophenol (PCP) production to that of the general population and to examine mortality risk by estimated exposure levels. METHODS: A retrospective cohort study which followed up workers' vital status from 1940 to 2011, with serum surveys to support estimation of historical dioxin exposure levels. RESULTS: Among the 2192 study subjects, there were nine deaths in TCP workers from acute non-lymphatic leukaemia [standardized mortality ratio (SMR) = 2.88, 95% confidence interval (CI) 1.32-5.47], four mesothelioma deaths (SMR = 5.12, 95% CI 1.39-13.10) and four soft tissue sarcoma (STS) deaths (SMR = 3.08, 95% CI 0.84-7.87). In PCP workers, there were eight deaths from non-Hodgkin's lymphoma (SMR = 1.92, 95% CI 0.83-3.79), 150 from ischaemic heart disease (SMR = 1.20, 95% CI 1.01-7.89) and five from stomach ulcers (SMR = 3.38, 95% CI 1.10-7.89). There were no trends of increased mortality with increased dioxin exposure except for STS and 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. This finding for STS should be interpreted with caution due to the small number of deaths and the uncertainty in diagnosis and nosology. CONCLUSIONS: While some causes of death were greater than expected, this study provides little evidence of increased risk when dioxin exposures are considered.

Cancer incidence among semiconductor and electronic storage device workers.

AIMS: To evaluate cancer incidence among workers at two facilities in the USA that made semiconductors and electronic storage devices. METHODS: 89 054 men and women employed by International Business Machines (IBM) were included in the study. We compared employees' incidence rates with general population rates and examined incidence patterns by facility, duration of employment, time since first employment, manufacturing era, potential for exposure to workplace environments other than offices and work activity. RESULTS: For employees at the semiconductor manufacturing facility, the standardised incidence ratio (SIR) for all cancers combined was 81 (1541 observed cases, 95% confidence interval (CI) 77 to 85) and for those at the storage device manufacturing facility the SIR was 87 (1319 observed cases, 95% CI 82 to 92). The subgroups of employees with > or =15 years since hiring and > or =5 years worked had 6-16% fewer total incidents than expected. SIRs were increased for several cancers in certain employee subgroups, but analyses of incidence patterns by potential exposure and by years spent and time since starting in specific work activities did not clearly indicate that the excesses were due to occupational exposure. CONCLUSIONS: This study did not provide strong or consistent evidence of causal associations with employment factors. Data on employees with long potential induction time and many years worked were limited. Further follow-up will allow a more informative analysis of cancer incidence that might be plausibly related to workplace exposures in the cohort.

Polymorphisms in HLA class I genes associated with both favorable prognosis of human immunodeficiency virus (HIV) type 1 infection and positive cytotoxic T-lymphocyte responses to ALVAC-HIV recombinant canarypox vaccines.

Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8(+) cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8(+) cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B*27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B*57 carriers reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B*27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4, P < 0.05) and B*57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013) and Env (39%; OR = 9.5, P = 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.