Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07-1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98-1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.

Large cohort studies in the U.S. and in Europe suggest that air pollution may increase lung cancer risk. Biomarkers can be useful to understand the mechanisms and to characterize high-risk groups. Here we describe biomarkers of exposure, in particular DNA adducts as well as markers of early damage, including mutagenicity, other endpoints of genotoxicity and molecular biomarkers of cancer. Several studies found an association between external measures of exposure to air pollution and increased levels of DNA adducts, with an apparent levelling-off of the dose-response relationship. Also, numerous experimental studies in vitro and in vivo have provided unambiguous evidence for genotoxicity of air pollution. In addition, due to the organic extracts of particulate matter [especially various polycyclic aromatic hydrocarbon (PAH) compounds], particulate air pollution induces oxidative damage to DNA. The experimental work, combined with the data on frequent oxidative DNA damage in lymphocytes in people exposed to urban air pollution, suggests 8-oxo-dG as one of the important promutagenic lesions. Lung cancer develops through a series of progressive pathological changes occurring in the respiratory epithelium. Molecular alterations such as loss of heterozygosity, gene mutations and aberrant gene promoter methylation have emerged as potentially promising molecular biomarkers of lung carcinogenesis. Data from such studies relevant for emissions rich in PAHs are also summarized, although the exposure circumstances are not directly relevant to outdoor air pollution, in order to shed light on potential mechanisms of air pollution-related carcinogenesis.

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Lifestyle and physical workloads increase the risk of LBP and lumbar radicular pain. Walking and cycling may have preventive potential for LBP. This article is protected by copyright. All rights reserved.

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Both low back pain (LBP) and obesity are common public health problems, yet their relation remains controversial. The aim of this study was to investigate the associations between weight-related factors and the prevalence of LBP in young adults in Finland. Participants in the ongoing Cardiovascular Risk in Young Finns Study aged 24-39 years were included (N = 2,575). In 2001, 31.2% of men and 39.5% of women reported LBP with recovery within a month or recurrent or continuous pain during the preceding 12 months. For women only, those with higher body mass index, waist circumference, hip circumference, waist-to-hip ratio, serum leptin level, and C-reactive protein level showed an increased prevalence of LBP. With all weight-related factors in the model, only waist circumference was related to LBP in women. For women, the odds ratios of LBP were 1.2 (95% confidence interval: 0.8, 1.8) for a waist circumference of 80-87.9 cm and 1.8 (95% confidence interval: 1.0, 3.2) for a waist circumference of > or =88 cm compared with a waist circumference of <80 cm. This association was independent of C-reactive protein, leptin, and adiponectin levels. The authors' findings in a relatively young population suggest that abdominal obesity may increase the risk of LBP in women.

Germline mutations in the fumarate hydratase (FH) gene at 1q43 predispose to dominantly inherited cutaneous and uterine leiomyomas, uterine leiomyosarcoma, and papillary renal cell cancer (HLRCC syndrome). To evaluate the role of FH inactivation in sporadic tumorigenesis, we analyzed a series of 299 malignant tumors representing 10 different malignant tumor types for FH mutations. Additionally, 153 uterine leiomyomas from 46 unselected individuals were subjected to and informative in loss of heterozygosity analysis at the FH locus, and the five (3.3%) tumors displaying loss of heterozygosity were subjected to FH mutation analysis. Although mutation search in the 299 malignant tumors was negative, somatic FH mutations were found in two nonsyndromic leiomyomas; a splice site change IVS4 + 3A>G, leading to deletion of exon four, and a missense mutation Ala196Thr. The occurrence of somatic mutations strongly suggests that FH is a true target of the 1q43 deletions. Although uterine leiomyomas are the most common tumors of women, specific inactivating somatic mutations contributing to the formation of nonsyndromic leiomyomas have not been reported previously. Taking into account the apparent risk of uterine leiomyosarcoma associated with FH germline mutations, the finding raises the possibility that also some nonsyndromic leiomyomas may have a genetic profile that is more prone to malignant degeneration. Our data also indicate that somatic FH mutations appear to be limited to tumor types observed in hereditary leiomyomatosis and renal cell cancer.

Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited condition characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation.