The Western Australian Mesothelioma Registry: Analysis of 60 years of cases.

BACKGROUND AND OBJECTIVE: Australia introduced a partial ban on asbestos consumption in 1984. There is continuing concern about exposure to asbestos in the built environment and non-occupational exposures. The aim of this study was to describe epidemiological trends of mesothelioma in Western Australia (WA) over the 60 years since the first case was recorded. METHODS: Every case of mesothelioma notified to the WA Cancer Registry is reviewed by an expert panel. Data include demographic and clinical variables including principal mode of asbestos exposure and age at first exposure. Trends over time for survival, latency and pathological subtype of mesothelioma where analysed. Incidence rates for cases exposed during home renovation where calculated. RESULTS: Two thousand seven hundred ninety-six cases of mesothelioma were identified with males comprising the majority (n = 2368, 84.7%). The median (IQR) age at diagnosis was 70 (62-78) years, and median latency of 47 (38-55) years. Pleural mesothelioma was recorded in 2620 (93.7%) cases with the epithelioid subtype most prevalent (n = 1730, 61.9%). Overall, median survival was 298 (128-585) days and latency 46 (37-54) years, both effectively doubling over the study period. Non-occupational exposures were proportionally higher in females (52.6%), compared with males (9.5%). Home renovation was the primary exposure in 227 (8.1%) cases, with number of cases and incidence rate ratio peaking in 2005/09 but subsequently decreasing. CONCLUSION: The annual number of cases of mesothelioma in WA may have hit a plateau. The majority of females have non-occupational exposures and incidence rates from home renovation exposure may have peaked, suggesting the ban on asbestos has been effective.

Comparison of outcomes following a cytological or histological diagnosis of malignant mesothelioma.

BACKGROUND: Survival with the epithelioid subtype of malignant mesothelioma (MM) is longer than the biphasic or sarcomatoid subtypes. There is concern that cytology-diagnosed epithelioid MM may underdiagnose the biphasic subtype. This study examines survival differences between patients with epithelioid MM diagnosed by cytology only and other subtypes diagnosed by histology. METHODS: Demographics, diagnosis method, MM subtype and survival were extracted from the Western Australia (WA) Mesothelioma Registry, which records details of all MM cases occurring in WA. RESULTS: A total of 2024 MM cases were identified over 42 years. One thousand seven hundred forty-four (86.2%) were male, median (IQR) age was 68.6 (60.4-77.0) years. A total of 1212 (59.9%) cases were identified as epithelioid subtype of which 499 (41.2%) were diagnosed using fluid cytology only. Those with a cytology-only diagnosis were older than the histology group (median 70.2 vs 67.6 years, P<0.001), but median survival was similar (cytology 10.6 (5.5-19.2) vs histology 11.1 (4.8-19.8) months, P=0.727) and Cox regression modelling adjusting for age, sex, site and time since first exposure showed no difference in survival between the different diagnostic approaches. CONCLUSIONS: Survival of cytologically and histologically diagnosed epithelioid MM cases does not differ. A diagnostic tap should be considered adequate to diagnose epithelioid MM without need for further invasive testing.

Risk factors for malignant mesothelioma in people with no known exposure to asbestos.

OBJECTIVES: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other exposures which may cause MM. METHODS: Cases with no known asbestos exposure were selected from the WA Mesothelioma Register (WAMR). Matched controls were selected from hospital patients admitted for conditions unrelated to asbestos. Occupational histories were coded by an industrial hygienist. Data were analyzed using conditional logistic regression. RESULTS: Thirty-eight MM participants and 134 controls were recruited. Risk of MM was increased (OR = 3.1, 95%CI 1.0-9.6) after no known, but likely, exposure to asbestos at work. CONCLUSIONS: Because of its extensive use, few people in WA have never been exposed to asbestos. Unrecognized exposure may cause most MM cases initially regarded as "no exposure." Am. J. Ind. Med. 60:432-436, 2017. © 2017 Wiley Periodicals, Inc.

Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers.

The asbestos induced cancer malignant mesothelioma (MM) is difficult to diagnose and has a poor prognosis. MM is an immunological cancer, therefore autoantibodies may be suitable biomarkers and associated with prognosis. We used Protoarray(®) microarrays to determine immune responses to 8798 antigens in 10 MM and 10 asbestos exposed controls and developed diagnostic panels using 17 antigens from this. The AUC of these panels were independently tested in these 10 MM patients and controls and in a validation group of 36 controls and 35 MM patients using luminex assays; none of the antigens identified were validated. Immune responses to RAB38 were associated with a better prognosis.

Effect of N-acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: a double-blind, randomized clinical trial.

BACKGROUND AND OBJECTIVE: Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed individuals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos. METHODS: A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation. RESULTS: Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified. CONCLUSIONS: No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation.

The mental health of asbestos-exposed subjects with pleural abnormalities.

PURPOSE: To examine the effect of knowledge of radiographic abnormalities on the mental health of asbestos-exposed people with and without pleural abnormalities. METHODS: Subjects were former asbestos mine and mill workers and residents of the mining town who had participated in an annual health review program. Pleural abnormalities (pleural plaques, diffuse pleural thickening and asbestosis) were determined from plain chest X-rays. All Participants completed a questionnaire on mental health status (SF-12) and locus of control (LOC). RESULTS: There were no significant differences between asbestos-exposed people with and without radiographic abnormalities for either the SF-12 mental health score or LOC. However, the asbestos-exposed cohorts had lower mental health scores compared with a random sample of the local population. CONCLUSION: The presence of pleural abnormalities did not further affect the mental health of asbestos-exposed people beyond a decrement associated with exposure per se.

Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia.

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3-2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.

Pleurodesis outcome in malignant pleural mesothelioma.

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.

All-cause mortality and cancer incidence among adults exposed to blue asbestos during childhood.

BACKGROUND: There are few data on the long-term health outcomes of exposure to asbestos in childhood. This study investigated cancer and mortality of adults exposed to blue asbestos as children. METHODS: Data linkage to relevant health registries was used to identify cancers and mortality in a cohort of adults (n = 2,460) that had lived in an asbestos mining town during their childhood (<15 years). RESULTS: There were 217 (93 female) incident cancers and 218 (70 female) deaths among the cohort. Compared with the Western Australian population females had elevated mesothelioma, ovarian and brain cancers, and increased "all cause" and "all cancer" mortality. Males had elevated mesothelioma, leukemia, prostate, brain, and colorectal cancers, and excess mortality from "all causes," "all cancers," circulatory disease, diseases of the nervous system, and accidents. CONCLUSION: Exposure to blue asbestos in childhood is associated with an increased risk of cancer and mortality in adults.

Increasing incidence of malignant mesothelioma after exposure to asbestos during home maintenance and renovation.

OBJECTIVE: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation. DESIGN, SETTING AND PARTICIPANTS: Using the Western Australian Mesothelioma Register, we reviewed all cases of MM diagnosed in WA from 1960 to the end of 2008, and determined the primary source of exposure to asbestos. Categories of exposure were collapsed into seven groups: asbestos miners and millers from Wittenoom; all other asbestos workers; residents from Wittenoom; home maintenance/renovators; other people exposed but not through their occupation; and people with unknown asbestos exposure; or no known asbestos exposure. Latency periods and age at diagnosis for each group were calculated and compared. RESULTS: In WA, 1631 people (1408 men, 223 women) were diagnosed with MM between 1960 and 2008. Since 1981, there have been 87 cases (55 in men) of MM attributed to asbestos exposure during home maintenance and renovation, and an increasing trend in such cases, in both men and women. In the last 4 years of the study (2005-2008), home renovators accounted for 8.4% of all men and 35.7% of all women diagnosed with MM. After controlling for sex and both year and age at diagnosis, the latency period for people exposed to asbestos during home renovation was significantly shorter than that for all other exposure groups, but the shorter follow-up and difficulty recalling when exposure first occurred in this group may partly explain this. CONCLUSIONS: MM after exposure to asbestos during home renovation is an increasing problem in WA, and these cases seem to have a shorter latency period than other types of exposure. MM cases related to renovation will probably continue to increase because of the many homes that have contained, and still contain, asbestos building products.

The Wittenoom legacy.

The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.

Age and sex differences in malignant mesothelioma after residential exposure to blue asbestos (crocidolite).

BACKGROUND: Blue asbestos was mined and milled at Wittenoom, Western Australia, from 1943 until 1966. Various public records were used to establish a cohort of residents of the nearby township. Mine tailings were distributed throughout the town. AIMS: To report the incident number of malignant mesotheliomas that have occurred in residents of the town who did not work at the mine or mill; and to determine if female subjects are more susceptible to asbestos exposure than male subjects, and if children are more susceptible than adults. SUBJECTS AND METHODS: A total of 4,768 residents of the town of Wittenoom have been followed up in cancer and death registries. RESULTS: There were 67 cases of mesothelioma, and 64 deaths with mesothelioma to the end of 2002. The mortality rate with mesothelioma increased with increasing residence duration, time since first exposure, and estimated cumulative exposure. The mesothelioma mortality rate was consistently lower for female subjects when compared with male subjects, but the dose-response curve was steeper for female subjects. The rate was lower in those first exposed as children compared with those first exposed at > or = 15 years of age. The dose-response slope for asbestos exposure and mortality from mesothelioma was not different between those who were first exposed as children than those who were first exposed at > or = 15 years of age. CONCLUSIONS: Former residents of a crocidolite mining town have a high rate of mesothelioma. The rate is higher in male subjects and those > or = 15 years of age at first exposure, but women have a steeper dose-response curve.

Plasma vitamin concentrations and incidence of mesothelioma and lung cancer in individuals exposed to crocidolite at Wittenoom, Western Australia.

Increased rates of death from asbestos-related diseases have been reported in former workers and residents exposed to crocidolite (blue asbestos) at Wittenoom (Western Australia). The relationships between plasma concentrations of retinol, carotene and vitamin E and incidence of mesothelioma and lung cancer in a cohort of people from this town were examined. The relationships were evaluated by survival analyses using data obtained at the first visit, at each visit and with the rate of change of each vitamin during the period of follow-up. Of 1953 study participants, 65 developed mesothelioma during the follow-up, and 47 developed lung cancer. A lower incidence of mesothelioma was related to plasma concentrations of retinol at the first visit [hazard ratio (HR)=0.63, 95% confidence interval=0.41-0.99], and to measurements at each visit (HR=0.71, 95% confidence interval=0.50-1.00). Plasma carotene concentrations at the first measurement, but not during the follow-up period, were associated with lower incidence of lung cancer in men and in workers. No significant associations were found between carotene concentrations and incidence of mesothelioma. Vitamin E concentrations were not significantly associated with mesothelioma or lung cancer incidence. These findings suggest that people with chronically low plasma levels of retinol have increased risk of developing mesothelioma and lung cancer.

Asbestos-related disease from recycled hessian superphosphate bags in rural Western Australia.

OBJECTIVES: To describe the dissemination of asbestos fibres within the Western Australian community. METHODS: A case report. RESULTS: A 60-year-old female was referred for investigation of calcified pleural plaques. On questioning, she recalled exposure to asbestos as a child on the family farm. She had shaken hessian bags prior to recycling to the fertiliser supplier. Her father survived to 90 years. Her mother died from malignant pleural mesothelioma. Four of five siblings had shaken the bags, two had radiographic evidence of pleural plaques while two others had not had recent chest x-rays. CONCLUSIONS: It appears that the use of recycled hessian bags for the fertiliser industry was endemic in the State during the period 1943-66. It is possible that many farmers and their families have had similar exposure to asbestos. IMPLICATIONS: The risk of developing an asbestos-related disease is not restricted to any specific social or employment groups within the Australian community.

Incidence of malignant mesothelioma in Aboriginal people in Western Australia.

OBJECTIVES: To describe the incidence of malignant mesothelioma (MM) in Aboriginal people in Western Australia (WA) and determine the main routes of exposure to asbestos in this population. METHODS: All MM cases in Western Australia, as well as the primary source of asbestos exposure, are recorded in the WA Mesothelioma Register. Aboriginal cases up to the end of 2013 were extracted from the register and compared with non-Aboriginal cases with respect to the primary means/source of exposure. Age-standardised incidence rates for each decade from 1980 were calculated for both Aboriginals and non-Aboriginals. Age-standardised mortality rates were calculated for the period 1994-2008 and compared with international rates. RESULTS: There were 39 cases (77% male) of MM among WA Aboriginal people. Twenty-six (67%) were a direct result of the mining of crocidolite at Wittenoom and the subsequent contamination of the surrounding lands. Of the non-Aboriginal MM cases (n = 2070, 86.3% male), fewer than 25% can be attributed to Wittenoom. Aboriginals had consistently higher 10-year incidence rates than non-Aboriginals and, when compared to world populations, the highest mortality rate internationally. CONCLUSION: When incidence rates in Aboriginal people are compared with non-Aboriginal people, the Wittenoom mining operation has had a disproportionate effect on MM incidence in the local Aboriginal population.

Plasma retinol, carotene and vitamin E concentrations and lung function in a crocidolite-exposed cohort from Wittenoom, Western Australia: a cohort study.

BACKGROUND: Increased rates of death from asbestos related diseases have been reported for people previously employed in the mining and milling operations at Wittenoom (Western Australia), and people who lived in the nearby town, where they were environmentally exposed to crocidolite. METHODS: Annual measurements of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and plasma concentrations of retinol, carotene and vitamin E have been made since 1992. Mixed effects models were used to examine the associations between lung function and the plasma vitamin levels of retinol, carotene and vitamin E. RESULTS: After adjusting for potential confounders, higher plasma retinol and carotene concentrations were significantly associated with higher levels of lung function at entry into the study, while vitamin E concentrations were associated with lower entry lung function. Retinol was associated with a less steep decline of lung function over time, while carotene concentrations were associated with an increased decline of lung function over time and vitamin E levels were not associated with changes of lung function over time. CONCLUSION: These results support a beneficial relationship between plasma concentrations of retinol on the levels and rates of change of lung function, while showing no such consistent beneficial effect for plasma levels of beta-carotene or vitamin E.

Plasma concentrations of retinol, carotene, and vitamin E and mortality in subjects with asbestosis in a cohort exposed to crocidolite in Wittenoom, Western Australia.

OBJECTIVE: We sought to examine the relationships between plasma concentrations of retinol, carotene, and vitamin E and mortality associated with asbestosis in people previously exposed to crocidolite. METHODS: Cox regression modeling was applied to examine these relationships at the first measurement of each vitamin, at the measurement at each visit, and with the rate of change of each vitamin during the follow-up. RESULTS: There were 76 deaths of people with asbestosis during the follow-up period and 1885 subjects censored. Mortality in subjects with asbestosis was inversely related to plasma levels of retinol and Vitamin E concentrations and to their rate of increase during the follow-up. Carotene concentrations at first visit were associated with lower mortality but not during the follow up period. CONCLUSIONS: Chronically low levels of these vitamins are associated with an increased risk of dying with asbestosis.

Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.

Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.