Meta-analyses of occupational exposure as a painter and lung and bladder cancer morbidity and mortality 1950-2008.

The International Agency for Research on Cancer (IARC) classified occupational painting as a human carcinogen based on lung and bladder cancers; however, no specific exposures were implicated. The authors conducted comprehensive meta-analyses of the epidemiological literature on occupational painting and these cancers. The authors abstracted study results and confounder information, and used quantile plots and regression models to evaluate heterogeneity and publication bias. Summary risk estimates were derived and sensitivity analyses performed to evaluate smoking, socioeconomic status (SES), and exposure variables. Where applicable, a Bayesian approach was used to externally adjust for smoking, a major risk factor for both cancers. For lung cancer cohort mortality studies, publication bias and heterogeneity were seen, and earlier studies reported higher risk estimates than later studies. Overall lung cancer summary risk estimates were 1.29 for case-control and 1.22 and 1.36 for cohort morbidity and mortality studies, respectively, and risk estimates for bladder cancer were 1.28 for case-control and 1.14 and 1.27 for cohort morbidity and mortality studies, respectively (all statistically significant). Risks did not differ between painters and mixed occupations. Nonsignificant summary estimates resulted for lung and bladder cancers when controlling for SES, or externally adjusting for smoking in lung cancer studies. Summary risks varied by control source for case-control studies. Residual confounding by smoking and SES, lack of exposure group effect, and publication bias limit the ability of the meta-analyses to explain associations observed between occupational painting and lung and bladder cancers. Given the long latencies for lung and bladder cancers, these weak associations, if real, may not be elucidated through studies of occupational painting today.

Identification of a novel peptidoglycan hydrolase CwlM in Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a major global pathogen whose threat has increased with the emergence of multidrug-resistant strains. The cell wall of M. tuberculosis is thick, rigid, and hydrophobic, which serves to protect the organism from the environment and makes it highly impermeable to conventional antimicrobial agents. There is little known about cell wall autolysins (also referred to as peptidoglycan hydrolases) of mycobacteria. We identified an open reading frame (Rv3915) in the M. tuberculosis genome designated cwlM that appeared consistent with a peptidoglycan hydrolase. The 1218-bp gene was amplified by PCR, cloned and expressed in E. coli strain HMS174(DE-3), and its gene product, a 47-kDa recombinant protein, was purified and partially characterized. Purified CwlM was able to lyse whole mycobacteria, release peptidoglycan from the cell wall of Micrococcus luteus and Mycobacterium smegmatis, and cleave N-acetylmuramoyl-L-alanyl-D-isoglutamine, releasing free N-acetylmuramic acid. These results indicate that CwlM is a novel autolysin and identify cwlM as the first, to our knowledge, autolysin gene identified and cloned from M. tuberculosis. CwlM offers a new target for a unique class of drugs that could alter the permeability of the mycobacterial cell wall and enhance the effectiveness of treatments for tuberculosis.