Christensen BC, Houseman EA, Godleski JJ, Marsit CJ, Longacker JL, Roelofs CR, Karagas MR, Wrensch MR, Yeh RF, Nelson HH, Wiemels JL, Zheng S, Wiencke JK, Bueno R, Sugarbaker DJ, Kelsey KT.

Department of Community Health, Center for Environmental Health and Technology, Brown University, 70 Ship Street, Providence, RI 02903, USA.

Abstract

Mechanisms of action of nonmutagenic carcinogens such as asbestos remain poorly characterized. As pleural mesothelioma is known to have limited numbers of genetic mutations, we aimed to characterize the relationships among gene-locus-specific methylation alterations, disease status, asbestos burden, and survival in this rapidly fatal asbestos-associated tumor. Methylation of 1505 CpG loci associated with 803 cancer-related genes were studied in 158 pleural mesotheliomas and 18 normal pleura. After false-discovery rate correction, 969 CpG loci were independently associated with disease status (Q < 0.05). Classifying samples based on CpG methylation profile with a mixture model approach, methylation classes discriminated tumor from normal pleura (permutation P < 0.0001). In a random forests classification, the overall misclassification error rate was 3.4%, with <1% (n = 1) of tumors misclassified as normal (P < 0.0001). Among tumors, methylation class membership was significantly associated with lung tissue asbestos body burden (P < 0.03), and significantly predicted survival (likelihood ratio P < 0.01). Consistent with prior work, asbestos burden was associated with an increased risk of death (hazard ratio, 1.4; 95% confidence interval, 1.1-1.8). Our results have shown that methylation profiles powerfully differentiate diseased pleura from nontumor pleura and that asbestos burden and methylation profiles are independent predictors of mesothelioma patient survival. We have added to the growing body of evidence that cellular epigenetic dysregulation is a critical mode of action for asbestos in the induction of pleural mesothelioma. Importantly, these findings hold great promise for using epigenetic profiling in the diagnosis and prognosis of human cancers.

Glossary

prognosis

(prog-no-sis) a prediction of the course of disease; the outlook for the cure of the patient. For example, women with breast cancer that was detected early and who received prompt treatment have a good prognosis.

pleura

(pler-uh) the membrane around the lungs and lining of the chest cavity. (Pleural mesothelioma.)

gene

a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

tissue

a collection of cells, united to perform a particular function.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Archimandriti DT, Dalavanga YA, Cianti R, Bianchi L, Manda-Stachouli C, Armini A, Koukkou AI, Rottoli P, Constantopoulos SH, Bini L.

Department of Pneumonology, Medical School, University of Ioannina, Ioannina, Greece.

Abstract

Inhabitants of Metsovo, NW Greece, have been exposed to an asbestos whitewash, resulting in malignant pleural mesothelioma (MPM) and pleural calcifications (PCs). Interestingly, those with PCs (PC⁺) are less prone to MPM. They also have lymphocytic alveolitis, and differences in bronchoalveolar lavage (BAL) proteins, compared with those without pleural calcifications (PC^-). This may mean a different response to the fiber leading to different susceptibility to neoplasia. To further evaluate this, a proteomic analysis of BAL proteins was performed. Proteomic analysis (2D-electrophoresis/Mass Spectrometry) of BAL in Metsovites nonoccupationally exposed to asbestos revealed increased albumin fragments, alpha1-antitrypsin, S100-A9 and HSP27, suggesting ongoing inflammation. In those without pleural calcifications, increased expression of acid ceramidase, glutathione-S-transferase and presence of calcyphosin, all involved in cell cycle regulation and death as well as in the detoxification of mutagenic and toxic agents, lend further support to our thesis of possible “protection against neoplasia” in Metsovites with pleural calcifications.

Glossary

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Moore AJ, Parker RJ, Wiggins J.

Department of Respiratory Medicine, Wexham Park Hospital, Wexham, Slough, Berkshire, UK. a.moore@ic.ac.uk

Abstract

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational “environmental” exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Glossary

prevalence

a measure of the proportion of persons in the population with a certain disease at a given time.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

benign

(be-nine) not cancer; not malignant.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

tunica vaginalis

The serous sheath of the testis and epididymis, derived from the peritoneum; it consists of outer parietal and inner visceral serous layers.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

pleural effusion

an abnormal accumulation of fluid, usually caused by trauma or disease, in the pleural space.

ascites

(uh-sigh-tees) excess fluid accumulation in the abdominal (peritoneal) cavity.

Sherwood AL, Mutsaers SE, Peeva VK, Robinson C, deSilva CJ, Swanson NR, Lake RA.

National Centre for Asbestos Related Diseases, University of Western Australia, Perth, Australia.

Abstract

Objectives: Mesotheliomas occur in occult serous cavities after chronic exposure of mesothelial cells to asbestos fibres. Molecular events that contribute to the development of this cancer are therefore not readily accessible for study. We have used in vitro culture systems to study and compare induced and spontaneous transformation events in primary mouse mesothelial cells.

Materials and Methods: Mouse mesothelial cells were cultivated until small populations of proliferating cells emerged from senescing cultures. Spontaneously transformed cultures of cells were characterized and compared to malignantly transformed cells.

Results: Human mesothelial cells had a finite lifespan of 10-15 population doublings when cultured in vitro; mouse mesothelial cells typically exhibit this same pattern. Here, we show that mouse mesothelial cells can be cultured for extended periods and that these cells can transform spontaneously. Lines of spontaneously transformed cells generated in this study are immortal and growth factor-independent. They display the salient characteristic features of transformation, including increased proliferation rate, lack of contact inhibition, aneuploidy and ability to grow in anchorage-independent conditions. A subset of these cell lines developed into tumours in syngeneic mice. Comparative gene expression analysis demonstrated that spontaneously transformed cell lines were more closely related to neoplastic cells than to primary cells.

Conclusion: These findings have implications for interpretation of in vitro transformation studies, demonstrating broad similarity between spontaneous and induced genetic changes.

Glossary

gene

a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

Park EK, Hannaford-Turner KM, Hyland RA, Johnson AR, Yates DH.

Research and Education Unit, Workers’ Compensation Dust Diseases Board of NSW, Sydney, Australia.

Abstract

Asbestos is a fibrous silicate which is recognized as causing a variety of lung disorders including malignant mesothelioma of the pleura, lung cancer and asbestosis. Asbestos use has been banned in most developed countries but exposure still occurs under strict regulation in occupational settings and also occasionally in domestic settings. Although the hazards of asbestos are well known in developed countries, awareness of its adverse health effects is less in other parts of the world, particularly when exposure occurs in non-occupational settings. Experience of asbestos use and its adverse heath effects in developed countries such as Australia have resulted in development of expertise in the diagnosis and treatment of asbestos-related diseases as well as in screening and this can be used to help developing countries facing the issue of asbestos exposure.

Keywords: Asbestos, Mesothelioma, Asbestos-related diseases, Occupational exposure, Public health

Glossary

screening

the search for disease, such as cancer, in people without symptoms. For example, the principal screening measure for breast cancer is mammography. Screening may refer to coordinated programs in large populations.

pleura

(pler-uh) the membrane around the lungs and lining of the chest cavity. (Pleural mesothelioma.)

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Pancaldi C, Balatti V, Guaschino R, Vaniglia F, Corallini A, Martini F, Mutti L, Tognon M.

Department of Morphology and Embryology, Section of Cell Biology and Molecular Genetics, University of Ferrara, Ferrara, Italy.

Abstract

Objective: Asbestos is considered the main agent in causing the onset of the malignant pleural mesothelioma (MM), a fatal cancer of increasing incidence worldwide. Other factors may contribute to the onset/progression of MM, such as genetic predisposition and infection by oncogenic viruses, like simian virus 40 (SV40). SV40 was administered to human populations mainly with SV40-contaminated anti-polio vaccines. SV40 footprints have been detected in specific human tumours, including MM, and in healthy blood donors. The aim of this study was to verify the presence of SV40 sequences in buffy coats of healthy blood donors, inhabitants of Casale Monferrato, where MM is 10 times more prevalent compared to other areas.

Methods: DNA from 148 buffy coats of healthy blood donors were qualitatively and quantitatively PCR analyzed for SV40 sequences.

Results: SV40 sequences were detected in 24 out of 148 (16%) samples. Quantitative real time PCR analyses carried out in SV40-positive samples indicated a viral copy number in the range of 10-10,000 per 100,000 cells.

Conclusions: SV40 sequences are present in blood samples of healthy donors from Casale Monferrato with a prevalence similar to that reported in previous investigations of healthy donors from asbestos-free areas. Altogether these data suggest that SV40 is circulating in the human population.

Glossary

prevalence

a measure of the proportion of persons in the population with a certain disease at a given time.

predisposition

susceptibility to a disease that can be triggered under certain conditions. For example, some women have a family history of breast cancer and are therefore more likely (but not necessarily destined) to develop breast cancer.

DNA

(dee-ok-see-ri-bo-new-CLAY-ic) abbreviation for deoxyribonucleic acid. DNA holds genetic information on cell growth, division, and function.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

virus

very small organisms that cause infections. Viruses are too small to be seen with a regular microscope. They reproduce only in living cells.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Pairon JC, Andujar P, Matrat M, Ameille J.

INSERM Unité 841, Créteil, France. JC.Pairon@chicreteil.fr

Abstract

Lung cancer and pleural mesothelioma are the most common occupational cancers.

Recent epidemiological studies have estimated that the fraction attributable to occupational factors varies from 13 to 29% for lung cancer in men and is about 85% for pleural mesothelioma in men. Previous occupational exposure to asbestos is the most common occupational exposure in these cancers. Mesothelioma immediately leads the clinician to look for past asbestos exposure. In contrast, the search for an occupational exposure that should be routine in all cases of lung cancer, is generally more difficult because of the number of occupational aetiological factors and the absence of criteria that allow distinction of an occupational cancer from a tobacco related one.

Therefore attention should be paid to the identification of occupational exposure in order to set up primary prevention programmes to prevent exposure still present in the working environment and, on the other hand, to identify the subjects entitled to the acknowledgement of occupational disease and/or to obtain the compensation available to asbestos victims.

Keywords: Asbestos, Silicon dioxide, Occupational diseases, Lung, Carcinogens

Glossary

DES

abbreviation for diethylstilbestrola (die-eth-l-steh-BES-ter-ol),  synthetic form of estrogen.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Schneider F, Sporn TA, Roggli VL.

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. frank.schneider@duke.edu

Abstract

This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.

Keywords: amosite; amphiboles; asbestos; crocidolite; mesothelioma

Glossary

detection

finding disease. Early detection means that the disease is found at an early stage, before it has grown large or spread to other sites. Note many forms of cancer can reach an advanced stage without causing symptoms. Mammography can help to find breast cancer early, and the PSA blood test is useful in finding prostate cancer.

tissue

a collection of cells, united to perform a particular function.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Reid A, Heyworth J, de Klerk N, Musk AW.

Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Alison.Reid@uwa.edu.au

Abstract

Objectives: Knowledge of mortality patterns following exposure to asbestos has been determined mostly from cohort studies of men who were exposed to asbestos in their workplace. Women are more likely to have obtained their asbestos exposure domestically or from their environment.

Methods: 2552 women and girls are documented to have lived in the blue asbestos mining and milling township of Wittenoom between 1943 and 1992 and were not involved in asbestos mining or milling. Quantitative asbestos exposure measurements were derived from periodic dust surveys undertaken in the industry and around the township. Death records were obtained for the period 1950–2004. Standardised mortality ratios (SMRs) were calculated to compare the Wittenoom women’s mortality with that of the Western Australian female population.

Results: There were 425 deaths, including 30 from malignant mesothelioma. There was excess mortality for all causes of death (SMR = 1.13), all neoplasms (SMR = 1.42), symptoms, signs and ill defined conditions (SMR = 6.35), lung cancer (SMR = 2.15) and pneumoconiosis (SMR = 11.8). Mortality from cancer of the ovary (SMR = 1.52), upper aerodigestive cancers (SMR = 2.70) and tuberculosis (SMR = 5.38) was increased but not significantly. The risk of death from mesothelioma was increased, but not significantly, in residents known to have lived with or washed the clothes of an Australian Blue Asbestos Company asbestos worker (HR = 2.67, 95% CI 0.77 to 9.21; HR = 2.61, 95% CI 0.85 to 7.99, respectively).

Conclusion: Women who were former residents of Wittenoom, exposed to asbestos in their environment or in their home, have excess cancer mortality, including mesothelioma, compared with the Western Australian female population.

Glossary

mortality

a measure of the rate of death from a disease within a given population.

epidemiology

(ep-uh-deem-ee-AHL-uh-gee) the study of diseases in populations by collecting and analyzing statistical data. In the field of cancer, epidemiologists look at how many people have cancer; who gets specific types of cancer; and what factors (such as environment, job hazards, family patterns, and personal habits, such as smoking and diet) play a part in the development of cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

Okuda M, Kashio M, Tanaka N, Masuno T, Kamei J, Tsuyuguchi I.

Osaka Hospital, Anti-Tuberculosis Association, Osaka Branch.

Abstract

We report a case of non-tuberculous mycobacteriosis (NTM) with pleurisy in a 75-year-old man. The patient was admitted with a diagnosis of pneumonia. Chest radiography and CT scans revealed a tumorous shadow that increased rapidly in size despite treatment with antibiotics. Bronchoalveolar lavage fluid (BALF) disclosed numerous asbestos bodies, suggesting dense exposure and pulmonary silicosis. The tumorous chest shadow remained undiagnosed. Repeated microscopic examination of sputum and BALF revealed no acidophilic-bacilli. Diagnostic pneumonectomy was performed to further explore the nature of the tumorous shadow on chest radiography. Ziehl-Neelsen staining of excised lung tissue disclosed no acid-bacilli; however, the washed fluid of the tissue specimen showed acid-fast bacilli that were subsequently verified as M. avium by in vitro culture. The X-ray findings in our case were not consistent with NTM or specific for disease due to asbestos inhalation. A final diagnosis of NTM was confirmed via open biopsy of the lung. Our case suggests that in addition to tuberculosis, NTM should be taken into consideration as a complication of silicosis.

Glossary

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

biopsy

(buy-op-see) the removal of a sample of tissue to see whether cancer cells are present. There are several kinds of biopsies. In some, a very thin needle is used to draw fluid and cells from a lump. In a core biopsy, a larger needle is used to remove more tissue.

tissue

a collection of cells, united to perform a particular function.