Genetic polymorphisms of xenobiotic-metabolizing enzymes influence the risk of pulmonary emphysema.

BACKGROUND: Pulmonary emphysema is a smoking-induced condition of the lung. Genetically determined differences in the activities of enzymes that metabolize oxidative agents are suspected to modify individual susceptibility to emphysema, as well as other smoking-related pulmonary disorders. OBJECTIVES: We investigated whether polymorphisms in selected xenobiotic-metabolizing enzyme genes predispose to emphysematous changes and airflow limitation among Finnish Caucasian construction workers. METHODS: PCR-based methods were used to analyze nine common polymorphisms in EPHX1, GSTM1, GSTM3, GSTP1, GSTT1, and NAT2 genes among 988 Finnish construction workers. The genotype data were compared with different emphysematous signs confirmed with high-resolution computed tomography and with forced vital capacity and forced expiratory volume in 1 s. For this, linear and logistic regression analyses, adjusted for the potential confounders, were used. RESULTS: The EPHX1 Tyr113His polymorphism was associated with emphysematous changes (P=0.007), including paraceptal (P=0.039), panlobular (P=0.013), and bullae (P=0.003) type changes. The GSTM3 promoter polymorphism was associated with forced expiratory volume in 1 s/forced vital capacity ratio (P=0.010), and the GSTT1 genotype with emphysematous signs (P=0.008), including paraceptal (P=0.015), panlobular (P=0.031), and bullae-type (P=0.045) changes. In further analysis, the GSTT1 deletion was found to pose a two-fold overall risk for having emphysematous changes (odds ratio: 2.01; 95% confidence interval: 1.33-3.03), and almost a four-fold risk for having severe emphysematous changes (odds ratio: 3.70; 95% confidence interval: 2.15-6.36). CONCLUSION: The results indicate a significant modifying role for GSTT1 gene polymorphism in the individual risk and severity of emphysematous changes.

Season of birth and lung fibrosis among workers exposed to asbestos.

The season of birth has been suggested to influence the development of some diseases, but its role in lung fibrosis seems to not have been studied previously. The aim of this study was to investigate the relation between the season of birth and fibrotic abnormalities as detected radiologically in high-resolution computed tomography (HRCT) among workers exposed to asbestos. The HRCT examination was performed on 528 study subjects. Multiple ordinal regression analysis adjusting for covariates was used to study the relations between birth month or season and radiological fibrosis signs. Subjects born in autumn or winter had more extensive fibrotic changes than those born in spring or summer. This applied to all fibrotic changes, apart from subpleural nodules, but only the overall fibrosis score, septal lines, and honeycombing showed statistically significantly higher values in comparison to spring births. The highest scores were detected among those born in autumn and winter months (September-February). These results suggest that there are differences in fibrotic radiological abnormalities according to the season of birth in adults exposed to asbestos. Several hypotheses could explain the observed findings, including the effects of early respiratory infections, cold temperature, and differences in air pollution levels, as well as some metabolic and hormonal effects.

Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer.

UNLABELLED: Lung cancer specimens display recurrent copy number aberrations in distinguished chromosomal regions as compared with normal lung cells. Such alterations have been utilized in design of fluorescence in situ hybridization (FISH) probe sets in attempts to improve the cytological diagnosis of lung cancer. One of such probe sets, LAVysion, detects copy number changes in the centromeric region of chromosome 6 (CEP6), and regions 5p15, 8q24, and 7p12, often gained in lung cancer. METHODS: We evaluated the feasibility of the LAVysion multi-color probe set in detection of individuals at high risk of lung cancer by applying the FISH probe set on smears prepared of induced sputa obtained from 20 lung cancer patients, 43 asbestos-exposed workers, 21 heavy tobacco smokers, and 15 healthy never-smokers. The hybridized sputum smears were examined using fluorescence microscopy and the number of signals in epithelial cells was examined throughout the hybridized area. Additionally, we review here the previous studies using LAVysion probe set. RESULTS: The FISH probe set was slightly more sensitive than cytology alone in detecting lung cancer. No significant differences in copy number gain were found between high-risk individuals and healthy never-smokers. The proportions of individuals with copy number gains in sputa among the lung cancer patients, asbestos-exposed workers, tobacco smokers, and never-smokers were 50, 20, 12, and 27%, respectively, when three or more cells with a copy number gain detected by at least two different probes was used as the cut-off point. In comparison, the sensitivity of cytology in detecting lung cancer was 44%. In the lung cancer patients the number of abnormal cells by FISH correlated well with the cytologic atypia class (Spearman rank correlation coefficient 0.77, p<0.01). Using multivariant variance analysis, gains in CEP6, 5p15, 8q24 and 7p12 were not associated with smoking or asbestos exposure. CONCLUSIONS: FISH did not significantly exceed the sensitivity of sputum cytology in finding lung cancers. Significant differences were not found between sputa of asbestos-exposed individuals, heavy-smokers and never-smokers. More sensitive methods are needed for the follow-up of populations at high risk of contracting lung cancer.

Finnish Institute of Occupational Health (FIOH): prevention and detection of asbestos-related diseases, 1987-2005.

BACKGROUND: Between 1987 and 1992, the Finnish Institute of Occupational Health (FIOH) initiated and implemented the Asbestos Program that aimed at reducing asbestos-related risks. It was a cooperative effort between government authorities, labor market organizations, and health care and labor protection personnel. METHODS: During the Program and its follow-up since 1993 several preventive actions were taken, and considerable new legislation and official instructions were issued. RESULTS: Approximately 200,000 people in Finland have been exposed to asbestos in their work. Through the cooperative efforts of government, labor, health care and worker protection programs, the import of asbestos was ceased in 1993 with a few exceptions. Almost all imports ceased in 2005 following European Union directives. Regulation of asbestos abatement companies has been greatly increased. The occupational exposure limit has been reduced from 2.0 fibers/cm(3) to the present 0.1 fibers/cm(3). Asbestos-related diseases are closely monitored and education of health care providers regarding the occupational source of these conditions is now emphasized. CONCLUSIONS: The success of the primary goal of the Program, a reduction in asbestos-related morbidity, will not be fully realized for many decades.

Computed tomography screening for lung cancer in asbestos-exposed workers.

We conducted a computed tomography (CT) screening for lung cancer in a high-risk population. Six hundred and two workers (38-81 years, 97% smokers) with asbestos-related occupational disease were screened using spiral CT and chest radiography. The national cancer registry was checked for possible false negative cases. The screening detected 111 patients with non-calcified nodules >0.5 cm in diameter and 66 of them were referred for further hospital examination. We found five lung cancers (106 false positive cases) with a histological spectrum similar to the national, natural occurrence of the disease (two adeno, one squamous cell, one anaplastic and one metastatic carcinoma) and one peritoneal mesothelioma. Three cases were potentially operable (stage I-II). Unfortunately there was one false negative fine-needle aspiration biopsy (FNAB) with misinterpretation of the follow-up CT scan and another patient who refused further investigations after an inadequate FNAB. In the end only one patient with adenocarcinoma underwent surgery. After 3 years of follow-up two new lung cancers were reported to the cancer registry with no evidence of tumour in the retrospective analysis of the screening CT scan. The sensitivity of CT screening was 100%. CT was capable of detecting early lung cancer in asbestos-exposed patients with a lot of confusing pulmonary and pleural pathology. Due to the high number of positive findings attention should be paid to patient compliance and the follow-up protocols and patient selection in future screening programmes.