RESUMO
Previously we reported that in sheep dippers exposed to organophosphates the frequency of paraoxonase (PON1) polymorphisms differed between those with or without self-reported ill health. We have now examined whether polymorphisms in other genes involved in xenobiotic metabolism alter disease risk in this population. There were elevated but non-significant risks associated with the CYP2D6 WT genotype (odds ratio (OR) 1.47, 95% CI 0.83-2.60), or a GSTP1*B or *C allele (OR 1.37, 95% CI 0.88-2.01) or being GSTM1*2/GSTT1*2 homozygous (OR 1.61, 95% CI 0.74-3.48). Similar results were generally obtained after the exclusion of subjects to obtain a more homogenous case-referent population: for double null GSTM1 and GSTT1 homozygotes the OR was 2.06 (95% CI 0.85-2.04). In those also likely to have been exposed to diazinon, risks associated with a GSTP1*B or *C allele (OR 1.82, 95% CI 0.92-3.63) or a GSTM1*2/GSTT1*2 homozygous (OR 2.60, 95% CI 0.72-10.42) were elevated but not to a significant extent. Risk associated with PON1 genotype and phenotype varied with CYP2D6 and GSTP1 genotype but not consistently with a priori hypotheses. Further work is necessary to delineate more clearly pathways of organophosphate activation and non-PON1 pathways of detoxification and to confirm whether CYP and GST polymorphisms alter disease risk in populations exposed to organophosphates.
Assuntos
Arildialquilfosfatase/genética , Citocromo P-450 CYP2D6/genética , Predisposição Genética para Doença , Glutationa S-Transferase pi/genética , Exposição Ocupacional/efeitos adversos , Organofosfatos/efeitos adversos , Polimorfismo Genético , Agricultura , Animais , Genótipo , Glutationa Transferase/genética , Humanos , Inseticidas/efeitos adversos , Carneiro DomésticoRESUMO
AIMS: To investigate the hypothesis that long term exposure to excessive noise can increase the risk of ischaemic heart disease. METHODS: A case-control design, nested within a cohort of nuclear power workers employed at two sites in England over the period 1950-98, was used. Cases were men who died from ischaemic heart disease (ICD-9: 410-414) aged 75 or under; each was matched to a surviving control of the nearest age who joined the same site at the same time. Personal noise exposure was assessed retrospectively for each man by hygienists using (1) company work histories, (2) noise survey records from 1965-98, and (3) judgements about likely use of hearing protection devices. Men were classified into four groups according to their cumulative exposure to noise, with men whose exposure at the company never exceeded 85dB(A) for at least one year being considered "unexposed". Risks were compared via odds ratios (ORs) using conditional logistic regression and adjusted for systolic and diastolic blood pressure, height, BMI, and smoking, as measured at recruitment to the company. RESULTS: Analysis was based on 1101 case-control pairs. There was little difference between the exposure groups at recruitment. There was no evidence of increased risk at site A: the ORs for ischaemic heart disease mortality among low, medium, and high exposure categories, compared to unexposed men, being 1.04, 1.00, and 0.77. The corresponding ORs (95% CIs) at site B were 1.15 (0.81-1.65) 1.45 (1.02-2.06), and 1.37 (0.96-1.96). When the comparison was confined to men with at least five years of employment, these dropped to 1.07 (0.64-1.77), 1.33 (0.88-2.01), and 1.21 (0.82-1.79) respectively. CONCLUSIONS: The authors did not find statistically robust evidence of increased risk but the estimates at site B are consistent with those in a major cohort study. A strength of the present study is that the validity of noise estimation at site B has been demonstrated elsewhere.
Assuntos
Isquemia Miocárdica/etiologia , Ruído Ocupacional/efeitos adversos , Doenças Profissionais/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Inglaterra/epidemiologia , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Doenças Profissionais/mortalidade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Fatores de TempoRESUMO
AIMS: To investigate the validity of measures of noise exposure derived retrospectively for a cohort of nuclear energy workers for the period 1950-98, by investigating their ability to predict hearing loss. METHODS: Subjects were men aged 45-65 chosen from a larger group of employees--assembled for a nested case-control study of noise and death from ischaemic heart disease--who had had at least one audiogram after at least five years' work. Average hearing loss, across both ears and the frequencies 0.5, 1, 2, and 4 kHz, was calculated from the last audiogram for each man. Previous noise exposure at work was assessed retrospectively by three hygienists using work histories, noise survey records from 1965-98, and judgement about use of hearing protection devices. Smoking and age at the time of the audiogram were extracted from records. Differences in hearing loss between men categorised by cumulative noise exposure were assessed after controlling for age, smoking, year of test, and previous test experience. RESULTS: There were 186 and 150 eligible subjects at sites A and B of the company respectively who were employed for an average of 20 years. Compared to men with less than one year's exposure to levels of 85dB(A) or greater, hearing loss was greater by 3.7 dB (90% CI -2.6 to 10.1), 3.8 dB (90% CI -2.6 to 10.3), 7.0 dB (90% CI 1.1 to 12.9) and 10.1 dB (90% CI 4.2 to 16.0) in the lowest to highest categories of cumulative noise exposure at site B. In contrast, at site A, the corresponding figures were -2.2 dB, -2.4 dB, -1.8 dB, and -4.4 dB, with no confidence interval excluding zero. CONCLUSIONS: Noise estimation at one site was shown to have predictive validity in terms of hearing loss, but not at the other site. Reasons for the differences between sites are discussed.