Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands

As part of the "IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants," a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers.     

The Estonian study of Chernobyl cleanup workers: II. Incidence of cancer and mortality

A cohort of 4,742 men from Estonia who had participated in the cleanup activities in the Chernobyl area sometime between 1986 and 1991 and were followed through 1993 was analyzed with respect to the incidence of cancer and mortality. Incidence and mortality in the cleanup workers were assessed relative to national rates. No increases were found in all cancers (25 incident cases compared to 26.5 expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not differ statistically significantly from expectation for any individual cancer site or type, though lung cancer and non-Hodgkin's lymphoma both occurred slightly more often than expected. A total of 144 deaths were observed [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82-1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%) were suicides (SMR = 1.52; 95% CI = 1.01-2.19). Exposure to ionizing radiation while at Chernobyl has not caused a detectable increase in the incidence of cancer among cleanup workers from Estonia. At least for the short follow-up period, diseases directly attributable to radiation appear to be of relatively minor importance when compared with the substantial excess of deaths due to suicide.     

Risk of death from malignant neoplasms among paper mill workers

A cohort study was designed to evaluate the risk of death from malignant neoplasms among pulp and paper workers. This paper presents the evaluation of death risk among workers engaged only in the production of paper, paperboard and paper products. The cohort study covered 1,322 males and 1,914 females employed for, at least, one year in a big pulp and paper mill during the period 1968-90. The study of exposure to harmful factors revealed that concentrations of paper and paperboard dusts in this mill exceeded hygienic standards. The analysis of death risk by causes and gender of those under study was based on standardized mortality rate (SMR) calculated using the method of person-year observation. The general population of Poland was used as reference. The results do not confirm excess mortality from lung, stomach and hematopoietic cancers in paper mill workers reported by other authors. However, an elevated risk of bladder cancer in males (SMR = 491, two deaths) and brain cancer in females (SMR = 353, two deaths) was observed. Both SMR values were not statistically significant. Because of small number of deaths, risk according to exposure and latency was not evaluated.     

Lung cancer mortality in a French cohort of hard-metal workers

A cohort mortality study was carried out among workers of a plant producing hard metals using cobalt as a binder. This study was aimed at assessing possible lung cancer risks in relation with cobalt exposure. Seven hundred nine male workers with at least 1 year of employment were included in the cohort and followed for mortality from 1956 to 1989. Job histories were provided by the administration of the plant, whereas smoking habits were collected from medical records and by interview. The causes of deaths were ascertained from hospital and general practitioner records. The observed numbers of deaths (obs) were compared with the expected based on national rates with adjustment for age, sex, and calendar time (standardized mortality ratio; SMR). The overall mortality did not differ from that expected (obs = 75, SMR = 1.05), whereas mortality due to lung cancer was in significant excess (obs = 10, SMR = 2.13). This excess was higher among workers employed in the areas with the highest exposure (obs = 6, SMR = 5.03). No trend was observed, however, with duration of employment or time since first employment. Smoking data were available for 81% of the workers and 69% of the deceased and showed that smoking alone does not account for these lung cancer excesses, yet, because of the small numbers involved, no firm conclusion should be drawn from this study.     

Workplace risk factors for cancer in the German rubber industry: Part 2. Mortality from non-respiratory cancers

OBJECTIVES: To determine the mortality from non-respiratory cancers by work area among active and retired male workers of the German rubber industry. METHODS: A cohort of 11,633 male German workers was followed up for mortality from 1 January 1981 to 31 December 1991. Cohort members were active (n = 7536) or retired (n = 4127) on 1 January 1981 and had been employed for at least one year in one of five study plants producing tyres or technical rubber goods. Work histories were reconstructed from routinely documented "cost centre codes" and classified into six categories: I preparation of materials; II production of technical rubber goods; III production of tyres; IV storage and dispatch; V general service; VI others. Standardised mortality ratios (SMRs) and 95% confidence intervals (95% CIs), controlling for age and calendar year and stratified by work area (employment in respective work area for at least one year) and time related variables (year of hire, lagged years of employment in work area) were calculated from national mortality rates as the reference. RESULTS: Significant increases in mortality were found for pharyngeal cancer in work area IV (three deaths, SMR 486, 95% CI 101 to 1419), oesophageal cancer in work area III (11 deaths, SMR 227, 95% CI 114 to 407), and leukaemia in work areas I (11 deaths, SMR 216; 95% CI 108 to 387) and II (14 deaths, SMR 187; 95% CI 102 to 213). Furthermore, increased SMRs were found for stomach cancer in work area I (22 deaths, SMR 134; 95% CI 84 to 203), colon cancer in work area II (27 deaths, SMR 131, 95% CI 86 to 191), prostatic cancer in work area V (27 deaths, SMR 152, 95% CI 99 to 221), and bladder cancer in work areas IV (six deaths, SMR 253; 95% CI 93 to 551) and V (12 deaths, SMR 159, 95% CI 82 to 279). Mortality from cancer of the liver or gall bladder, pancreas and kidney, and from lymphomas was not substantially increased in any of the work areas. CONCLUSIONS: Mortality from cancer of several sites was associated with specific work areas. Some of these associations have been reported previously. Future analyses of our study will have to determine the role of specific exposures in the aetiology of these cancers.     

An evaluation of digital subtraction radiography for assessment of changes in position of the mandibular condyle

OBJECTIVES: This study evaluated the mortality experience of workers from the styrene-butadiene rubber industry. Concerns about a possible association of 1,3-butadiene and styrene with lymphohaematopoietic, gastrointestinal, and lung cancers prompted the investigation. METHODS: A retrospective follow up study was conducted of 15,649 men employed for at least one year at any of eight North American styrene-butadiene rubber plants. Analyses used standardised mortality ratios (SMRs) to compare styrene-butadiene rubber workers' cause specific mortalities (1943-91) with those of the United States and Ontario general populations. RESULTS: On average, there were 25 years of follow up per subject. The standardised mortality ratio (SMR) was 87 (95% confidence interval (95% CI) 85 to 90) for all causes of death combined and was 93 (95% CI 87 to 99) for all cancers. There was an excess of leukaemia (SMR 131, 95% CI 97 to 174), restricted to hourly workers (SMR 143, 95% CI 104 to 191). For causes of death other than leukaemia, SMRs were close to or below the null value of 100. Results by work area (process group) were unremarkable for non-Hodgkin's lymphoma, multiple myeloma, and stomach cancer. Maintenance workers had a slight increase in deaths from lung cancer, and certain subgroups of workers had more than expected deaths from cancer of the large intestine and the larynx. CONCLUSION: This study found an excess of leukaemia that is likely to be due to exposure to butadiene or to butadiene plus other chemicals. Deaths from non-Hodgkin's lymphoma, multiple myeloma, and stomach cancer did not seem to be related to occupational exposure. The excess deaths from lung cancer among maintenance workers may be due in part to confounding by smoking, which was not controlled for, and in part to an unidentified occupational exposure other than butadiene or styrene. Increases in cancer of the large intestine and larynx were based on small numbers, did not seem to be due to exposure to butadiene or styrene, and may be chance observations.     

Stress and HIV disease progression: psychoneuroimmunological framework

BACKGROUND AND METHODS: A retrospective cohort study was conducted to estimate the effects of low-level exposure to external (penetrating) radiation on cancer mortality among 4,563 workers monitored for external radiation between 1950 and 1993 at a nuclear research and production facility in Southern California. RESULTS: Of the 875 deaths that occurred before 1995, 258 were due to cancer as the underlying cause. External comparisons of male subjects with the U.S. white male population indicated that the workers had lower rates of dying from all causes and all cancers, but a higher rate of dying from leukemia. Internal comparisons of workers exposed at different dose levels, using risk-set analyses with adjustment for confounders, demonstrated an increased mortality rate in workers exposed to 200 mSv for hemato- and lymphopoietic cancers and for lung cancer. Mortality rates for total cancers and "radiosensitive" solid cancers increased monotonically with cumulative radiation dose, but no trends were observed for "nonradiosensitive" cancers. CONCLUSIONS: Despite possible residual confounding and low precision for estimating effects on specific cancers, these findings indicate that chronic, low-level radiation exposure may have more generalized carcinogenic effects than have been observed in most previous investigations. Such effects may have become evident as a result of the relatively long follow-up period in the present study.     

First analysis of mortality and occupational radiation exposure based on the National Dose Registry of Canada

A cohort mortality study of occupational radiation exposure was conducted using the records of the National Dose Registry of Canada. The cohort consisted of 206,620 individuals monitored for radiation exposure between 1951 and 1983 with mortality follow-up through December 31, 1987. A total of 5,426 deaths were identified by computerized record linkage with the Canadian Mortality Data Base. The standardized mortality ratio for all causes of death was 0.61 for both sexes combined. However, trends of increasing mortality with cumulative exposure to whole body radiation were noted for all causes of death in both males and females. In males, cancer mortality appeared to increase with cumulative exposure to radiation, without any clear relation to specific cancers. Unexplained trends of increasing mortality due to cardiovascular diseases (males and females) and accidents (males only) were also noted. The excess relative risk for both sexes, estimated to be 3.0% per 10 mSv (90% confidence interval 1.1-4.8) for all cancers combined, is within the range of risk estimates previously reported in the literature.     

Mortality and incidence of cancer among sewage workers: a retrospective cohort study

To study the incidence of and mortality from cancer among sewage workers a retrospective analysis was performed on a cohort of 656 men employed for at least one year at any one of 17 Swedish sewage plants during the years 1965-86. Assessment of exposure was done by classification of work tasks. Lower than expected total mortality (standardised mortality ratio (SMR) = 0.75, 95% confidence interval (95% CI) 0.58-0.97) and cardiovascular mortality (SMR = 0.61, 95% CI 0.39-0.91) was found. This was interpreted as a result of the healthy worker effect. For all cancers combined the mortality (SMR = 1.08, 95% CI 0.68-1.67) and morbidity (SMR = 1.02, 95% CI 0.72-1.38) were comparable with those of the general population. There were increased incidences for brain tumours (SMR = 2.19, 95% CI 0.45-6.39), gastric cancers (SMR = 2.73, 95% CI, 1.00-5.94), and renal cancers (SMR = 1.68, 95% CI = 0.35-4.90). For lung cancer the risk was reduced (SMR = 0.70, 95% CI 0.15-2.05). Allowance for a latency period of 10 years from the start of exposure did not change the pattern. Logistic modelling was used to search for exposure-response relations. In a logistic model with the confounder age forced in, renal cancer had a significant positive relation with a weighted sum of employment times, where the weights describe the classification of exposure. No exposure-response relations were found for brain tumors or gastric cancers. The increased risks are based on small numbers of cases. A future follow up will add more conclusive power to the study. Specific exposures need to be identified to allow for a better dose-response analysis.     

Determination of monensin, salinomycin and narasin in muscle, liver and eggs from domestic fowl using liquid chromatography-electrospray mass spectrometry

Historical records were used to reconstruct an outbreak of chlorance and acute liver toxicity due to chlorinated naphthalene exposure at a New York State plant which manufactured "Navy cables" during World War II. A cohort mortality study was conducted of the population (n = 9,028) employed at the plant from 1940 to 1944. Vital status was followed through December 31, 1985. The study found an excess of deaths from cirrhosis of the liver [observed (OBS) = 150; standardized mortality ratio (SMR) = 1.84; 95% confidence interval (CI) = 1.56-2.16]; cirrhosis deaths were elevated to a similar degree in the 460 individuals who had chlorance (OBS = 8; SMR = 1.51; CI = 0.65-2.98). The SMR for "non-alcoholic cirrhosis" (OBS = 83; SMR = 1.67; CI = 1.33-2.07) was similar to the SMR for "alcoholic cirrhosis" (OBS = 59; SMR = 1.96; CI = 1.49-2.53). There was no evidence for increased alcoholism in the overall cohort based on mortality from alcohol-related causes of death other than cirrhosis (SMR for esophageal cancer = 1.01 and for deaths from alcoholism = 0.99). We conclude that the excess mortality from cirrhosis of the liver observed in this cohort is due to the chronic effect of chlorinated naphthalene exposure.     

Stronger occipital cortical activation to lower than upper visual field stimuli. Neuromagnetic recordings

This article present the results of the extension of the follow-up of a cohort of workers employed in an Italian oil refinery. 1,583 workers employed in 1949-1982 in a northern Italy oil refinery plant were followed-up for mortality as of May 31, 1991. Environmental measurements documented potential exposure to benzene. Standardized mortality ratios (SMR) and their 95% confidence intervals (95% CI) were calculated using as references national (1949-1968) and regional mortality rates (1969-1991). Elevated mortality from lymphoma (seven deaths, SMR 190, 95% CI 76-391) and leukemia (eight deaths, SMR 225, 95% CI 97-443) was observed. No consistent trends by length of employment or time since first exposure were apparent. Nonetheless, the excess risk was particularly and significantly increased among workers with 15 or more years of employment, and 30 or more years since first employment. The findings of elevated mortality from leukemia and lymphoma are in agreement with those of other oil refinery studies. Chance, confounding, or other biases might have played a marginal, if any, role in determining the results. Exposure to benzene is a biologically plausible explanation.     

Postservice mortality of US Air Force veterans occupationally exposed to herbicides in Vietnam: 15-year follow-up

The US Air Force continues to assess the mortality of veterans of Operation Ranch Hand, the unit responsible for aerially spraying herbicides in Vietnam. The authors of this study found that the cumulative all-cause mortality experience of these veterans was not different from that expected (standardized mortality ratio (SMR) = 1.0). Overall, cause-specific mortality did not differ from that expected regarding deaths from accidents, cancer, or circulatory system diseases, but the authors found that there was an increased number of deaths due to digestive diseases (SMR = 1.7, 95% confidence interval (CI) 0.9-3.2). When analyzing by military occupation, they found an increase in the number of deaths caused by circulatory system diseases (SMR = 1.5, 95% CI 1.0-2.2) among enlisted ground personnel, the subgroup with the highest dioxin levels. Most of the increase in the number of deaths from digestive diseases was caused by chronic liver disease and cirrhosis, and more than half of the increase in the number of deaths from circulatory system diseases was a result of atherosclerotic heart disease. In the subgroup of Ranch Hand veterans who had survived more than 20 years since their military service in Southeast Asia, the authors found no significant increase in the risk of death due to cancer at all sites (SMR = 1.1) and a nonsignificant increase in the number of deaths due to cancers of the bronchus and lung (SMR = 1.3).     

Predictive tests of response to radiotherapy. Assessment and perspectives in 1997

A cohort study was carried out in order to evaluate the cancer risk in the asbestos-cement industry workers. The cohort consisted of workers employed in four asbestos-cement plants. One of those plants was established in 1924, the other three in the 1960s and 1970s. Currently only two of these plants continue their production. The plants used mainly chrysotile asbestos as well as crocidolite and amosite. Amphibolite asbestos was used before the mid-nineteen eighties in production of pressure pipes utilising about 15% of the total quantity of asbestos used. The measurements of the asbestos fibre concentration at work-sites have been taken occasionally since the mid 1980s, thus, the determination of a cumulative dose for individual persons in the cohort and the evaluation of the dose-effect relationship were not feasible. It could only be supposed that the concentrations at the preparatory work-site during first years of the plants' operation accounted for several tens fibres/cm3 in the production that employed the dry method. The cohort consisted of workers employed in the plant for at least three months between beginning of the plant during the post-war period, and 1980, that is during the period when amphibolite asbestos was in use. The retrospective observation was completed on 31 December 1991. The analysis of the death risk by causes was based on a standardized mortality ratios (SMRs) calculated using the person-years method. Statistical significance of SMRs was assessed by means of Poisson distribution one-sided test. The general population of Poland was used as the reference population to estimate the death risk. The cohort comprised 4,712 persons (3,563 males and 1,149 females). Of this number 4,500 persons (3,405 males and 1,095 females) were followed. The cohort availability were 95.5%. Male mortality, both total (473 deaths; SMR = 83) and due to malignant neoplasms (108 deaths; SMR = 86) was lower than in the general population. An excess of deaths from neoplasm of the pleura was by about 23 times higher (5 deaths; SMR = 2,288) and from neoplasm of the large intestine by two times higher (7 deaths; SMR = 214). Among females (41 deaths; SMR = 50) death risk was lower than in the reference population. At a low level of total mortality from neoplasms (13 deaths; SMR = 52) a statistically significant excess of deaths from neoplasm of the pleura (2 deaths; SMR = 2,112) was observed. In the plants investigated the analysis revealed a considerably diversified mortality from asbestos-related neoplasms. The incidence of pleura mesothelioma should be attributed to the use of considerable quantities of crocidolite asbestos and high concentrations of fibres in the air in plants II and IV, particularly during the first years after their establishment. In view of a long period of latency the excess of this neoplasm can be expected till 2020.     

Renal eco Doppler in pediatrics

In this study, the authors investigated mortality and cancer patterns among a group of individuals accidentally exposed to methyl chloride 32 y earlier. This group of 24 persons had survived the immediate intoxication, which had occurred on a trawler during a fishing trip. The authors selected a reference group, which contained five times as many individuals as the study group, from registers of crews, and they controlled for age, occupation, social class, and lifestyle factors. The authors established a record linkage through personal identification numbers with the national death register and cancer register, thus securing 100% follow-up. The Mantel-Haenszel point estimate (M-H) was 2.2, and the 95% confidence interval (CI) was 1.3-3.1 for all causes of death. There was an excess of deaths from cardiovascular diseases (M-H = 2.1, 95% CI = 1.2-3.8). This excess mortality was more prominent among deckhands who had been subject to higher exposure; risk ratios (RRs) were elevated for all causes of death (RR = 2.5, 95% CI = 1.0-5.7), as well as for cardiovascular diseases (RR = 3.9, 95% CI = 1.0-14.4). In addition, the authors noted elevated risks for all cancers (M-H = 1.5, 95% CI = 0.3-5.6) and for lung cancer (M-H = 2.7, 95% CI = 0.1-52.6). The authors concluded that exposure to methyl chloride may have contributed to the risk of cardiovascular disease. Investigators need to conduct further studies on groups exposed to methyl chloride to refute or confirm this result.     

Mortality among a cohort of electric utility workers, 1960-1991

Overall mortality trends among an electric utility workforce are examined. The study cohort (n = 40,335) included all workers with at least 1 year of work experience from 1960-1991; 3,753 deaths were observed in this cohort. Standardized mortality ratios (SMRs) and internal cohort analyses were used to assess mortality trends for the entire cohort and for specific occupational groups. Most SMRs were < or = 1.0 and were generally lower for noncancer (cardiovascular, COPD, and injuries) than for cancer mortality. Compared to office staff, rate ratios (RR) were higher for respiratory cancers for field staff [(RR = 2.3, 95% CI, 1.0-5.0) linecrew (RR = 2.2 95% CI, 1.5-3.1), and power plant occupations (RR = 2.4, 95% CI, 1.6-3.6)]. Nonmanagement occupations had rate ratios for motor vehicle injuries and all types of injuries, within a range of 2.5-4.7, with all lower CIs > 1.0. The healthy worker effect is an important factor in explaining the difference between SMR and internal cohort analyses results. The SMR results indicate that this workforce has lower rates for overall mortality, cardiovascular disease, cancer and nonintentional injury. A consistent finding in the internal cohort analyses that merits further research was higher mortality rates for respiratory cancer and injuries among nonoffice staff.     

Occupational low back pain: history and physical examination

The mortality experience of 7,119 workers who were employed at a Beaumont, Texas, refinery for at least 1 year between 1945 and 1987 was investigated. Mortality analyses based on standardized mortality ratios (SMRs) and 95% confidence intervals (95% CI) showed overall mortality was significantly lower than expected compared with the U.S. general population (SMR = 82, 95% CI = 79-86). Total cancer mortality was also lower than expected (SMR = 92, 95% CI = 84-100). Significant mortality deficits from several malignant and nonmalignant diseases were reported. A significant mortality increase in the broad category of lymphatic and hematopoietic cancers was found (SMR = 133, 95% CI = 103-170). This increase was attributed to a nonsignificant elevation in leukemia of all cell types combined (SMR = 139, 95% CI = 92-201) and a borderline significant increase in other lymphatic tissue cancer (SMR = 158, 95% CI = 101-235). The elevation in leukemia was confined to workers hired before 1950. Furthermore, the leukemia excess was shown to have peaked during the 1960s, with mortality no longer elevated post-1980. Analyses of cell type-specific leukemias showed a similar temporal pattern for acute myeloid leukemia (AML) which was not significantly elevated (SMR = 136, 95% CI = 59-268). Mortality from other leukemia cell types was similar to or lower than expected. Mortality from non-Hodgkin's lymphoma (NHL) (SMR = 140, 95% CI = 88-211) and multiple myeloma (MM) (SMR = 121, 95% CI = 55-230) were increased, but neither was statistically significant nor likely to be related to refinery employment. No death from asbestosis was reported, and mortality from mesothelioma and pulmonary fibrosis was lower than expected. Lung cancer mortality for the overall cohort was similar to expected. For the overall cohort, analyses by duration of employment and time since first employment showed no evidence of any trends for increasing cause-specific mortality. Separate analyses of male workers employed in operator jobs showed mortality patterns that were more favorable than those of the total cohort. Maintenance craftworkers showed statistically significant elevations in mortality for prostate cancer (SMR = 145, 95% CI = 107-194), leukemia (SMR = 179, 95% CI = 111-273), and other lymphatic tissue cancer (SMR = 233, 95% CI = 138-368). Detailed analyses indicated that, among maintenance craftworkers, mortality was elevated for AML, NHL, and MM, but none was significant. Furthermore, no upward trend by duration of maintenance jobs was observed. A small increase of lung cancer was observed among maintenance craftworkers (SMR = 120, 95% CI = 99-145), which was borderline significant. No relationship between lung cancer and duration of maintenance employment was found. In contrast, a deficit of pulmonary fibrosis was reported among maintenance craftworkers (SMR = 62, 95% CI = 17-159). These findings are discussed in conjunction with results from other refinery studies, and the limitations of the study are discussed.     

Mortality due to pancreatic and lymphopoietic cancers in chlorohydrin production workers

Men assigned to the chlorohydrin unit of Union Carbide's South Charleston plant in the Kanawha Valley of West Virginia were followed up for mortality from 1940 to the end of 1988. This 10 year update was conducted to verify previous findings of excesses of cancer among the 278 men assigned to the chlorohydrin unit, which primarily produced ethylene chlorohydrin from 1925 to 1957. This process produced ethylene dichloride and bischloroethyl ether as byproducts. Mean duration of assignment was 5.9 years and mean duration of follow up was 36.5 years. Standardised mortality ratios (SMRs) were calculated based on comparisons with the United States white male population. Duration-response trends were assessed by internal comparisons with two different groups of unexposed chemical workers in the Kanawha Valley. The evidence that the earlier finding of an excess of pancreatic cancer was work related is strengthened by the occurrence of two additional cases (0.9 expected). The SMR for pancreatic cancer was 492 (95% CI 158-1140), based on eight observed v 1.6 expected deaths. There were no additional deaths due to leukaemia, but the three to four-fold excess risk for lymphopoietic cancers persisted due to new cases of non-Hodgkin's lymphoma and a death from multiple myeloma. The SMR for lymphatic and haematopoietic cancers was 294 (eight observed v 2.7 expected; 95% CI 127-580). Pronounced increases in risk were seen for total cancer, pancreatic cancer, all lymphatic and haematopoietic cancers, and leukaemia with increasing durations of assignment to the chlorohydrin unit. Most of the cases were first assigned to the unit in the 1930s when chemical manufacturing was in its infancy and exposures were less controlled. These data are insufficient to identify conclusively the causative agent or agents. The weight of evidence, however, based on probable exposure, known toxicity of the chemicals, and animal responses suggest that high exposures to ethylene dichloride, perhaps in combination with other chlorinated hydrocarbons, is the most likely explanation.     

Bilaterally cleft lip, limb defects, and haematological manifestations: Roberts syndrome versus TAR syndrome

OBJECTIVES: To examine the causes of death among 1130 former workers of a plant in Tyler, Texas dedicated to the manufacture of asbestos pipe insulation materials. This cohort is important and unusual because it used amosite as the only asbestiform mineral in the production process. High level exposure of such a specific type was documented through industrial hygiene surveys in the plant. METHODS: Deaths were ascertained through various sources including data tapes from the Texas Department of Health and the national death index files. As many death certificates as possible were secured (304/315) and cause of death assigned. After select exclusions, 222 death certificates were used in the analysis. Causes of death were compared with age, race, and sex specific mortalities for the United States population with a commercial software package (OCMAP Version 2.0). RESULTS: There was an excess of deaths from respiratory cancer including the bronchus, trachea, and lung (standardised mortality ratio (SMR) 277 with 95% confidence interval (95% CI) 193 to 385). Four pleural mesotheliomas and two peritoneal mesotheliomas were identified. The analysis also showed an increasing risk of respiratory malignancy with increased duration of exposure including a significant excess of total deaths from respiratory cancer with less than six months of work at the plant (SMR 268 with 95% CI 172 to 399). CONCLUSIONS: The importance of the cohort lies with the pure amosite exposure which took place in the plant and the extended period of latency which has followed. The death certificate analysis indicates the pathogenicity of amosite, the predominant commercial amphibole used in the United States. These data confirm a link between amosite asbestos and respiratory malignancy as well as mesothelioma.     

Renal biopsy diagnosis in children presenting with haematuria

OBJECTIVES: This study considers the cause-specific mortality from cancer among art glass workers employed in 17 industrial facilities in Tuscany, Italy. METHODS: A cohort of 3390 workers, 3180 men and 210 women, employed at least 1 year, was taken from company payrolls. It was followed between the year each factory started operation, mostly the mid-1950s, and 31 December 1993. The cause-specific expected mortality from cancer was computed for men relative to Tuscany rates, specified for gender, 5-year age groups, and calendar year. Separate analyses were carried out for the job title of maker and former and for batch mixers. RESULTS: For 3180 men, the observed mortality was above the expected for larynx [standardized mortality ratio (SMR) 166, 90% confidence interval (90% CI) 90-282], lung (SMR 123, 90% CI 100-151), stomach (SMR 105, 90% CI76-142), and brain (SMR 150, 90%CI 71-282) cancer. Increases for these causes were also found for the makers and formers. Mortality from larynx and lung cancer increased with latency, and significantly increased SMR values were observed for > or =21 years since first exposure. The increasing pattern was also present after adjustment for smoking. CONCLUSIONS: The results showed consistently increased mortality from larynx and lung cancer in the overall cohort and among makers and formers. Stomach and brain cancer was also increased in the overall cohort and among the makers and formers.     

Obesity-independent hyperinsulinemia in nondiabetic first-degree relatives of individuals with type 2 diabetes

An increased incidence of systemic cancers has been described in some reports of familial atypical multiple mole-melanoma kindreds. If the gene defect underlying the familial atypical multiple mole-melanoma syndrome is not only important for the development of melanoma of the skin, the impact of the defect on life expectancy may be much higher than previously thought. We investigated all-cause mortality from 1830 to the present and causes of death from 1941 to 1994 in proven, obligate, and potential CDKN2 mutation carriers to obtain an estimate of the impact of a hereditary defect of the CDKN2 gene on mortality. From 1830 to 1994 there were 65 deaths, although only 42 deaths were expected [standardized mortality ratio (SMR) 1.6, 95% confidence interval (CI) 1.2-2.0] and the SMR doubled with calendar time. Excess mortality was shown in most of the families, but was confined to ages 35-70 y (SMR 2.1, 95%CI 1.5-2.9). Excess mortality could be fully attributed to cancer mortality, especially to pancreatic carcinoma and melanoma of the skin. There appeared to be some heterogeneity among the families, especially due to the specific cancer pattern within a family. The impact of the defect of the CDKN2 gene is rising over calendar time, mainly because the mortality in the general population has been falling. Excess mortality was not only due to melanoma, but also to pancreatic carcinoma. Therefore, follow-up programs of affected family members should not be confined to a regular check of the atypical nevi.