Iodine-based contrast media, multiple myeloma and monoclonal gammopathies: literature review and ESUR Contrast Media Safety Committee guidelines.

OBJECTIVES: Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury (PC-AKI) in these patients. METHODS: A systematic search in Medline and Scopus databases was performed for renal function deterioration studies in patients with MM or MG following administration of iodine-based contrast media. Data collection and analysis were performed according to the PRISMA statement 2009. Eligibility criteria and methods of analysis were specified in advance. Cohort and case-control studies reporting changes in renal function were included. RESULTS: Thirteen studies were selected that reported 824 iodine-based contrast medium administrations in 642 patients with MM or MG, in which 12 unconfounded cases of PC-AKI were found (1.6 %). The majority of patients had intravenous urography with high osmolality ionic contrast media after preparatory dehydration and purgation. CONCLUSIONS: MM and MG alone are not risk factors for PC-AKI. However, the risk of PC-AKI may become significant in dehydrated patients with impaired renal function. Hypercalcaemia may increase the risk of kidney damage, and should be corrected before contrast medium administration. Assessment for Bence-Jones proteinuria is not necessary. KEY POINTS: • Monoclonal gammopathies including multiple myeloma are a large spectrum of disorders. • In monoclonal gammopathy with normal renal function, PC-AKI risk is not increased. • Renal function is often reduced in myeloma, increasing the risk of PC-AKI. • Correction of hypercalcaemia is necessary in myeloma before iodine-based contrast medium administration. • Bence-Jones proteinuria assessment in myeloma is unnecessary before iodine-based contrast medium administration.

Gene and protein expression of CXCR4 in adult and elderly patients with chronic rhinitis, pharyngitis or sinusitis undergoing thermal water nasal inhalations.

BACKGROUND: Chronic rhinitis, pharyngitis and sinusitis are common health problems with a significant impact on public health, and are suspected to be influenced by ageing factors. Nasal inhalation with thermal water may be used to reduce symptoms, inflammation and drug intake. A pre-post clinical study was conducted in 183 consecutive adult and elderly patients with chronic rhinitis, pharyngitis or sinusitis, to evaluate whether thermal water nasal inhalations could improve their symptoms, clinical signs and rhinomanometry measurements, and influence inflammatory biomarkers levels in nasal epithelial cells. RESULTS: Participants profile revealed that they were aged on average (mean age and SD 60.6 ± 15.2 years, median 65, range 20-86, 86 aged ≤ 65 years (47%), 96 aged > 65 years (53%)) and extremely concerned about wellbeing. Older age was associated with better compliance to inhalation treatment. Total symptom and clinical evaluation scores were significantly ameliorated after treatment (p < 0.001), with no substantial difference according to age, while rhinomanometry results were inconsistent. Persistence of symptom improvement was confirmed at phone follow up 1 year later (n = 74). The training set of 48 inflammatory genes (40 patients) revealed a strong increase of CXCR4 gene expression after nasal inhalations, confirmed both in the validation set (143 patients; 1.2 ± 0.68 vs 3.3 ± 1.2; p < 0.0001) and by evaluation of CXCR4 protein expression (40 patients; 1.0 ± 0.39 vs 2.6 ± 0.66; p < 0.0001). CXCR4 expression was consistently changed in patients with rhinitis, pharyngitis or sinusitis. The increase was smaller in current smokers compared to non-smokers. Results were substantially unchanged when comparing aged subjects (≥ 65 years) or the eldest quartile (≥ 71 years) to the others. Other genes showed weaker variations (e.g. FLT1 was reduced only in patients with sinusitis). CONCLUSIONS: These results confirm the clinical impact of thermal water nasal inhalations on upper respiratory diseases both in adults and elders, and emphasize the role of genes activating tissue repair and inflammatory pathways. Future studies should evaluate CXCR4 as possible therapeutic target or response predictor in patients with chronic rhinitis, pharyngitis or sinusitis. TRIAL REGISTRATION: Communication to Italian Ministry of Health - ICPOM 000461. Registered 10/11/2014.

Gene-asbestos interaction in malignant pleural mesothelioma susceptibility.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor.

Worldwide interest in the comet assay: a bibliometric study.

The comet assay is a rapid, sensitive and relatively simple method for measuring DNA damage. A bibliometric study was performed to evaluate temporal and geographical trends, research quality and main areas of interest in scientific production in this field. A PubMed search strategy was developed and 7674 citations were retrieved in the period 1990-2013. Notably, the MeSH (Medical Subject Headings) term 'comet assay', officially introduced in 2000, is used by indexers only in two thirds of papers retrieved. Articles on the comet assay were published in 78 countries, spread over the 5 continents. The EU contributed the greatest output, producing >2900 articles with IF (42.0%) and totalling almost 10000 IF points, and was followed by USA. In the new millennium, research with this assay reached a plateau or slow decline in the most industrialised areas (USA, Germany, UK, Italy), while its use has boomed in emerging countries, with increases of 5- to 7-fold in the last 10 years in China, India and Brazil, for instance. This transition resulted in a slow decrease of scientific production quality, as the countries that increased their relative weight typically had lower mIFs. The most common MeSH terms used in papers using the comet assay referred to wide areas of interest, such as DNA damage and repair, cell survival and apoptosis, cancer and oxidative stress, occupational and environmental health. Keywords related to humans, rodents and cell culture were also frequently used. The top journal for the comet assay articles was found to be Mutation Research, followed by Mutagenesis. Most papers using the comet assay as a biomarker were published in genetic and toxicology journals, with a stress on environmental and occupational disciplines.

Effectiveness of complex interventions focused on quality-of-life assessment to improve palliative care patients' outcomes: a systematic review.

BACKGROUND: One of the most crucial palliative care challenges is in determining how patient' needs are defined and assessed. Assessing quality of life has been defined as a priority in palliative care, and it has become a central concept in palliative care practice. AIM: To determine to what extent interventions focused on measuring quality of life in palliative care practice are effective in improving outcomes in palliative care patients. DESIGN: Systematic review according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and hand searches. DATA SOURCES: MEDLINE, CINAHL, EMBASE, PsycINFO, and the Cochrane Library were searched for articles published until June 2012, and through hand searching from references lists of included articles. Only studies that included adult palliative care patients, in any palliative care clinical practice setting of care, and with an experimental, quasi-experimental, or observational analytical study design were eligible for inclusion. All studies were independently reviewed by two investigators who scored them for methodological quality by using the Edwards Method Score. RESULTS: In total, 11 articles (of 8579) incorporating information from 10 studies were included. Only three were randomized controlled trials. The quality of the evidence was found from moderate to low. Given a wide variability among patients' outcomes, individual effect size (ES) was possible for 6 out of 10 studies, 3 of which found a moderate ES on symptoms (ES = 0.68) and psychological (ES = 0.60) and social (ES = 0.55) dimensions. CONCLUSION: Effectiveness of interventions focused on quality-of-life assessment is moderate. Additional studies should explore the complexity of the real palliative care world more accurately and understand the effects of independent variables included in complex palliative care interventions.

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention.

Familiarity of physicians, translational researchers, nurses, and other health professionals with evidence-based medicine terms and resources.

Evidence-based medicine (EBM) is a central theme in health practice and training. The understanding of EBM technical terms and the familiarity with EBM resources were surveyed in four different health professional categories. A self-administered questionnaire on the familiarity with EBM terminology and resources was proposed to 218 health professionals (physicians, translational researchers, nurses, and others) working in the oncology field. Relationships between variable and familiarity were examined: Pearson χ(2) or exact Fisher test was used for the categorical variables and one-way ANOVA for the continuous ones. The odds of familiarity for subjects, who had followed or not at least one EBM course, were estimated fitting a multiple logistic regression model adjusted for age, gender, and profession. All subjects completed the questionnaire. The majority of health personnel seemed to lack a sound knowledge of key EBM terms and sources. Physicians showed the highest knowledge of terms, nurses the lowest. Physicians also declared the largest familiarity with the widest variety of resources, followed by others and the researchers. The most popular resource was PLNG, the Italian Guideline System. People who attended at least one EBM course showed consistently higher percentages of knowledge, but the association was irrelevant for nurses. The main perceived barrier to implement EBM in practice was a lack of personal time. Familiarity of health professionals with EBM terminology and resources is still limited to the medical field and needs to be improved. Increasing education may be pivotal, even if different approaches should be developed for different professional categories.

Bibliometric analysis of literature in cerebrovascular and cardiovascular diseases rehabilitation: growing numbers, reducing impact factor.

OBJECTIVES: To explore temporal trends, geographic distribution, and socioeconomic determinants of scientific production in the field of cerebrovascular and cardiovascular disease (CCD) rehabilitation. DATA SOURCES: Citations from 1967 to 2008 were downloaded from the PubMed database. Core of the search strategy was the key word cardiovascular diseases in the Medical Subject Headings major field with the subheading rehabilitation. Journal Citation Reports was used to assign an impact factor (IF). Demographic and economic data were retrieved from the International Monetary Fund. STUDY SELECTION: All articles retrieved were included in the bibliometric analysis. DATA EXTRACTION: The search strategy was validated on a random sample of the articles retrieved. The search quality reflected the level of error of the PubMed database. DATA SYNTHESIS: Publications retrieved were 10,379 and have grown 8.6 times in 40 years, faster than the all-diseases rehabilitation field (7.8 times), with a particularly steep growth for cerebrovascular diseases in the last 15 years (5 times). However, in the last decade, the articles' quality (IF) decreased. From 1994 to 2008, 3466 citations were retrieved; 44.4% came from the European Union and 30.3% from the United States. The highest mean IF was reported for France (4.127). The United Kingdom and some relatively small northern European Union countries had the best ratio of IF (sum) to resident population or to gross domestic product. The most frequently used key word was stroke, and 3 journals (Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, and Stroke) published one quarter of the articles. CONCLUSIONS: The overall scientific production in the field of CCD rehabilitation showed a steep growth in the last decade, especially because of cerebrovascular research. In the same period, a decrease in the overall IF was observed. The European Union and the United States contributed 3 of every 4 articles in the field, although some Asian countries showed promising performance.

Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium.

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984-2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.

Scientific production in cancer rehabilitation grows higher: a bibliometric analysis.

PURPOSE: The aim of the study was to evaluate scientific production in the field of cancer rehabilitation comparing publication trends and impact factor (IF) among countries. METHODS: The PubMed database was searched. Publications numbers and IF were evaluated both as absolute values and after standardization by population and gross domestic product (GDP). A dedicated software was developed to create a relational database containing all information about considered publications (Research Management System). RESULTS: Some 1,743 publications were retrieved from 1967 to 2008. Cancer rehabilitation publications have grown 11.6 times, while the whole field of disease rehabilitation has grown 7.8 times. Breast neoplasms, squamous cell carcinoma, treatment outcome, endosseous dental implantation, follow-up studies, and surgical flaps were the most commonly used keywords. From 1994 to 2008, 946 citations were retrieved: 36.8% came from the European Union (EU) (Germany, the UK, and the Netherlands ranking at the top) and 36.9% from the USA. The highest mean IF was reported for the USA (3.384) followed by Canada (3.265) and Australia (2.643). The EU has a mean IF of 0.839 with the Netherlands ranking first. Canada, Australia, and the USA had the best ratio between IF (sum) and resident population or GDP. CONCLUSIONS: Cancer rehabilitation is an expanding area with a growing scientific production. The rapidly ageing population, the higher number of cancer survivors, and the increasing need of resources for the after treatment of cancer patients contribute to explain the interest for this field.

Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rapidly fatal disease whose diagnosis, particularly through less invasive techniques such as analysis of pleural effusion, can be challenging. Currently, a commercially available diagnostic test based on microRNA (miRNA) expression patterns is purported to distinguish between mesothelioma and lung adenocarcinoma. Yet, the biological basis of this technology has not been reported in the literature, and little research has been aimed at determining how differential miRNA expression contributes to the differences in pathogenesis between these diseases, both of which can be caused by asbestos exposure. We sought to illuminate the molecular differences between mesothelioma and lung adenocarcinoma by using miRNA microarrays to identify patterns in the most differentially expressed miRNAs. From this, we identified a panel of miRNAs, including members of the miR-200 gene family, that were all downregulated in MPM compared to lung adenocarcinoma. Using the more sensitive detection method of quantitative RT-PCR on an independent series of tumors, we validated the specificity of these alterations in 100 MPMs and 32 lung adenocarcinomas. Statistical analysis reveals that these miRNAs exceed the current recommendations for biomarkers and could greatly aid in the differential diagnosis. Further examination led us to predict that they act as redundant regulators of wnt signaling and suggests a role for this pathway in tumor progression. This research points to novel approaches using miRNAs whose decreased expression is unique to mesothelioma as potentially suitable for rapid diagnosis and reveals prospective new targets for the treatment of this deadly disease.

Development of search filters for retrieval of literature on the molecular epidemiology of cancer.

OBJECTIVE: The available tools for searching literature in the area of molecular epidemiology of cancer, a relatively novel discipline, are largely unsatisfactory. The aim of this project was to develop two search filters in MEDLINE that would facilitate the retrieval of studies on cancer molecular epidemiology and to compare their performance. METHODS: Citations of all articles published in 2007 in three top journals in this area were hand-screened to establish a gold standard reference set of relevant papers. Two filters were created with this set: the first was based on the frequency of descriptors listed in the National Library of Medicine (NLM) Medical Subject Headings Thesaurus (MeSH terms) only, the second was based on the frequency of words in titles and abstracts (text-words), besides MeSH terms. The sensitivity, specificity, precision and accuracy rates of the two filters were calculated as performance measures. RESULTS: Out of all 1602 published articles, 344 were found to be pertinent to cancer molecular epidemiology; these formed the gold standard set. The first filter was the most specific (99%) and showed a good precision (93.2%), the second showed a higher sensitivity (78.2%) and accuracy (91.6%). CONCLUSION: The two filters proposed here represent a balance between sensitivity and specificity. Redefinition and elaboration of more appropriate NLM MeSH terms could greatly facilitate the retrieval of studies on the molecular epidemiology of cancer. Authors themselves could facilitate this by inserting adequate words in title or abstract of their articles.

Risk of malignant pleural mesothelioma and polymorphisms in genes involved in the genome stability and xenobiotics metabolism.

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mostly attributable to asbestos exposure. Many polymorphic genes encoding for xenobiotic and oxidative metabolism enzymes (XME) or involved in genome stability (GS) can modulate individual MPM risk in exposed populations. An association study was carried out in a case-control setting including 119 MPM patients and two groups of referent subjects (104 with and 695 without documented asbestos exposure). Forty-eight polymorphisms in XME genes and 75 in GS-genes were evaluated. Statistical analysis revealed some significant associations of studied polymorphisms with MPM risk, but most of them disappeared after applying Bonferroni correction (new threshold for statistical significance: p=4.07 x 10(-4)). On the other hand, the nucleotidic change 282C>T within NAT2 held the statistical significance (OR=3.54; 95% CI 1.75-7.16; p=0.0002), reinforcing existing evidences that describe genetic polymorphisms of NAT2 possibly involved in the etiology of the MPM.

Italian performance in cancer research.

AIMS AND BACKGROUND: Italian performance in cancer research from 2000 to 2007 was assessed and compared to that of the other 19 wealthiest countries in the world which carry out the bulk of cancer research. METHODS: Performance was evaluated quantitatively as the number of publications in 125 journals indexed as 'oncological' by Journal Citation Reports and qualitatively as the total impact factor (TIF). Number of publications and TIF were adjusted for the population and gross domestic product (GDP) of each country. The Scopus database was used as publication source. RESULTS: Italy ranked 5th, with the US ranking 1st, over the entire study period for number of cancer publications, which increased over that period. Italy ranked 4th in 2006-2007 for GDP-adjusted and 5th for population-adjusted publication number, loosing ground in the GDP-adjusted ranking and gaining ground in the population-adjusted ranking over the study period. When the quality of research publications was considered, in 2006-2007 Italy was in 5th place for crude TIF (US 1st), in 4th place for GDP-adjusted TIF (Sweden 1st), and in 6th place for population-adjusted TIF (Sweden 1st). Over the study period, Italy was stable for crude and population-adjusted TIF but declined somewhat for GDP-adjusted TIF. CONCLUSIONS: Italy's performance in cancer research over the eight years to 2008 was better than expected considering its GDP and population. Nevertheless, the slight decline evidenced by the present study should induce scientists and policy makers to find ways to reverse the situation.

The Role of Micronucleus Assay to Detect Genetic Instability in Respiratory Cancer Patients.

Asbestos represents the main risk factor for malignant pleural mesothelioma (PM) even if only a minority of exposed people develop this tumor, suggesting a significant role for genetic susceptibility. This study aims to evaluate micronuclei (MN) frequency as a biomarker of genome instability in peripheral blood lymphocytes of PM and lung cancer (LC) patients when compared with healthy controls (HCs) and patients with nonneoplastic respiratory diseases (RDs). Lymphocyte cytokinesis-block MN assay was carried out on 317 subjects. Mutagen sensitivity, measured by quantifying MN frequency after an in vitro challenge with ionizing radiation, was evaluated in 252 subjects. A significant increase in MN frequency was observed in cancer patients compared to HCs, with a mean ratio (MR) of 1.35 and 1.36 at baseline and 1.43 and 1.38 after irradiation in PM and LC patients, respectively. A positive (synergistic) interaction between asbestos exposure and disease status was observed for MN frequency after irradiation in PM patients with possible exposure to asbestos (MR = 1.62). The evidence of increased genetic damage in cancer cases confirms lymphocyte cytokinesis-block MN assay as a sensitive predictor of the role of genetic instability in carcinogenic processes.

Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region.

INTRODUCTION: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. METHODS: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. RESULTS: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. CONCLUSIONS: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.

The CREST biorepository: a tool for molecular epidemiology and translational studies on malignant mesothelioma, lung cancer, and other respiratory tract diseases.

OBJECTIVES: The Cancer of RESpiratory Tract (CREST) biorepository was established to investigate biological mechanisms and to develop tools and strategies for primary and secondary prevention of respiratory tract cancer. The CREST biorepository is focused on pleural malignant mesothelioma, a rare and severe cancer linked to asbestos exposure whose incidence is particularly high in the Ligurian region. METHODS: The CREST biorepository includes biological specimens from (a) patients with pleural malignant mesothelioma and lung cancer, (b) patients with nonneoplastic respiratory conditions, and (c) control subjects. Whole blood, plasma, serum, lymphocytes, pleural fluid, saliva, and biopsies are collected, and a questionnaire is administered. Collection, transportation, and storage are done according to international standards. RESULTS: As of January 31, 2008, the overall number of subjects recruited was 1,590 (446 lung cancer, 209 pleural malignant mesothelioma, and 935 controls). The biorepository includes a total of 10,055 aliquots (4,741 serum; 3,082 plasma; 1,599 whole blood; 633 pleural fluid; and 561 lymphocytes) and 107 biopsies. Demographic, clinical, and epidemiologic information is collected for each subject and processed in a dedicated database. CONCLUSIONS: The CREST biorepository is a valuable tool for molecular epidemiology and translational studies. This structure relies on a network of contacts with local health districts that allows for an active search for patients. This is a particularly efficient approach, especially when the object of the study is a rare cancer type. The CREST experience suggests that the presence of limited resources can be overcome by the biorepository specialization, the high quality of the epidemiologic information, and the variety of samples.

Genetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor.

BACKGROUND: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM. METHODS: Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Zi (FHSi). RESULTS: The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHSi allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion. CONCLUSIONS: The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.

Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases.

Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes.

DNA damage and genomic instability among workers formerly and currently exposed to asbestos.

Objectives Despite an asbestos ban in the European Union, exposure to asbestos still represents an occupational risk. Biomarkers of DNA damage and genomic instability in groups exposed to asbestos may contribute to the identification of subgroups/subjects at higher risk. Methods A cross-sectional study was conducted on 468 male individuals (80 working in occupational settings with potential exposure to asbestos fibers, 202 retired workers with past exposure, and 186 non-exposed controls) to compare genomic instability, cell proliferation and differentiation level using the non-invasive micronucleus buccal cytome assay. Data on demographic variables, lifestyle, and occupational history were collected with a standardized questionnaire. Micronuclei (MN) and other biomarkers of DNA damage and genomic instability were scored in a minimum of 2000/1000 cells per individual, respectively. Results Univariate and multivariate analysis showed opposite associations of MN frequency with current and former exposure. Compared to unexposed controls, workers with current potential exposure to asbestos had 55% lower MN frequency [95% confidence interval (CI) 71-29%, P<0.001] while those with past exposure had 34% higher MN frequency (95% CI 1-77%, P<0.001). The frequency of cells with condensed chromatin and binucleated cells was elevated among formerly exposed workers. The multivariate analysis did not reveal any actual confounders, although lower MN frequency was observed among subjects eating fresh fruit or vegetables every day or taking vitamin supplements. Conclusions Active workers with potential exposure to asbestos fibers did not show increased genomic damage. On the contrary, workers exposed in the past experienced a persistently elevated genomic instability, which may be used for risk assessment at subgroup or individual level.