Dario Consonni | Fond. IRCCS Istituto Nazionale dei Tumori (original) (raw)
Papers by Dario Consonni
International Journal of Environmental Research and Public Health, Mar 13, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Benzene is a human carcinogen and a ubiquitous pollutant of outdoor and indoor air. For the defin... more Benzene is a human carcinogen and a ubiquitous pollutant of outdoor and indoor air. For the definition of exposure to low benzene level, and for the evaluation of health risk posed by this exposure, the identification of suitable, specific and sensible biological markers is needed. This research compared the capability to discriminate the exposure of three biomarkers of benzene: t,t-muconic acid, and S-phenylmercapturic acid and urinary benzene. Gasoline filling attendants (N = 78), urban policeman (N = 77) e and subjects working in urban environment, designed as controls (N = 58) were recruited for the study. Air and urine samples (pre and end shift) were collected for each subject. Smoking habit was investigated by the use of a questionnaire and by determination of urinary cotinine. This study was part of a larger European investigation on human exposure to low level of benzene and its potential effects. Median personal exposure to benzene during the work shift in filling attendants, urban policeman and controls was 61 (44-478), 22 (9-316) and 6 (2-115) µg/m3, respectively. Significant differences were found among groups. End-shift t,t-muconic acid was 73 (5-518), 129 (5-909) and 40 (5-1089) µg/L. End-shift S-phenylmercapturic acid was 6.6 (0.2-25), 5.9 (0.2-14) and 5.0 (0.2-14) µg/L. End-shift urinary benzene was 603 (42-5111), 220 (25-4246) and 154 (15-4615) ng/L. A significant correlation was found between urinary benzene, but not t,t-muconic acid or S-phenylmercapturic acid, and personal exposure to benzene. All the investigated biomarkes were strongly influenced by cigarette smoking that resulted an important source of personal exposure to benzene, and whose importance could overcome that of the occupational exposure. The comparison among t,tmuconic acid, S-phenylmercapturic acid and urinary benzene showed that, in the investigated range of exposure, only urinary benzene was useful to discriminate the airborne exposure.
Annals of Work Exposures and Health, Feb 25, 2022
In occupational epidemiology, job coding is an important—but time-consuming—step in assigning exp... more In occupational epidemiology, job coding is an important—but time-consuming—step in assigning exposure. We implemented a tool (i.e. a crosswalk) to translate occupation codes from the Italian (ISTAT-CIP-91, n = 6319 five-digit job codes) to the International Standard Classification of Occupations (ISCO-68, n = 1881 five-digit job codes). The former is currently used in Italy for various purposes (e.g. in the National Mesothelioma Registry). The latter has been used in several studies on occupational cancers because it facilitates communication of results to the scientific community and, most importantly, because some job exposure matrices (JEMs) are based on international codes. Three authors created a table containing the crosswalk structure, providing an interpretation for each of the ISTAT-CIP-91 codes job descriptions and then manually recoding them according to ISCO-68. Two other authors independently revised it. The performance of the final version was assessed by comparison with results obtained by manual ISCO-68 coding performed in two previous case-control studies on asbestos and mesothelioma. More specifically, the automatically obtained ISCO-68 codes were merged with a JEM (DOM-JEM). The resulting individual asbestos exposure estimates (ever versus never exposed) were compared to those originally obtained (using the same DOM-JEM) from manual translation of ISTAT-CIP-91 to ISCO-68 (considered as the ‘gold standard’). In the first study, among 159 peritoneal mesothelioma cases (400 job codes), Cohen’s kappa was 0.91, sensitivity 0.95, and specificity 0.96. In the second study, among 716 pleural mesothelioma cases and controls (4400 job codes) kappa was 0.86, sensitivity 0.94, and specificity 0.91. Performance was better among in women. For men, performance was lower among cases than among controls (kappa 0.70, sensitivity 0.95, specificity 0.72 versus kappa 0.87, sensitivity 0.97, and specificity 0.92). In conclusion, the proposed tool allowed a rapid translation of thousands of job codes with good to excellent accuracy. The table containing ISTAT-CIP-91 codes and job descriptions and the corresponding ISCO-68 codes and job descriptions is made publicly available and can be freely used for epidemiological analyses in Italy and international collaborations.
American Journal of Transplantation, Jul 1, 2020
International Journal of Environmental Research and Public Health, 2022
The PRIMATE study is an Italian translational research project, which aims to identify personaliz... more The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational...
Cancer Epidemiology, 2019
Background: There is inadequate evidence to determine whether there is an effect of alcohol consu... more Background: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. Methods: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. Results: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This Jshaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). Conclusions: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.
International journal of cancer, May 24, 2017
It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship... more It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversel...
British Journal of Haematology, 2016
Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the ... more Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the pathogenetic mechanism is not clear and data are contradictory, probably because of study heterogeneity and the multifactorial nature of the pathogenesis. We retrospectively analysed 73 adult TM patients to evaluate the prevalence of pulmonary dysfunction in adult TM and investigate relationships with iron load. All patients underwent body plethysmography and carbon monoxide diffusion (DLCO) was assessed in 63, in addition to blood tests, echocardiogram and T2* myocardial and liver magnetic resonance imaging. Restrictive lung disease was present in 26 (35Á6%) patients. Serum ferritin levels were higher in patients with restrictive pattern (1526 lg/l vs. 975 lg/l, P = 0Á05). Restrictive lung disease did not correlate with cardiac or liver iron overload. However, considering only patients with serum ferritin >2500 lg/l, those with restrictive pattern also had heart (T2* 14Á28 AE 9Á99 ms vs. 31Á59 AE 7Á43 ms) and liver iron overload (LIC 16Á02 AE 8Á44 mg vs. 5Á02 AE 2Á69 mg Fe/g dry weight) compared to those without restrictive pattern. Twenty-five patients (39Á7%) had decreased DLCO. No correlation was observed with iron parameters. In our data restrictive pattern was predominant; we observed a relationship with serum ferritin levels suggesting that iron, particularly its chronic effect, could play a role in the pathogenesis of pulmonary disease.
Cancer Research, 2011
Background. Exposure to occupational carcinogens is an important preventable cause of lung cancer... more Background. Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. Methods. We estimated lung cancer risk associated with occupational carcinogens using a new validated job-exposure matrix (JEM), in the Environment And Genetics in Lung cancer Etiology (EAGLE) study, a large (2100 cases and 2120 controls) population-based case-control study conducted in Lombardy, Italy, between 2002-2005. The JEM translated lifetime work-histories coded into standard job-titles into never, low, and high exposure levels for six known/suspected occupational lung carcinogens. We calculated odds ratios (OR) and 95% confidence intervals (CI) in men (1537 cases and 1617 controls), by multiple logistic regression, adjusted for potential confounders, e.g., tobacco smoking and co-exposure to JEM carcinogens. We estimated the Population Attributable Fraction (PAF) as impact measure. Results. Exposure to asbestos (OR=1.76, 95%CI=1.42 to 2.18), crystalline silica (OR=1.31, 95%CI=1.00 to 1.71), or nickel-chromium (OR=1.18, 95%CI=0.90 to 1.53) was associated with increased risk even at low exposures, with positive trends for intensity and duration. We found an excess risk for exposure to polycyclic aromatic hydrocarbons only among highly exposed workers (OR=1.64, 95%CI=0.99 to 2.70). The PAFs for any exposure to asbestos, crystalline silica and nickel-chromium were 18.1%, 5.7%, and 7.0%, respectively, corresponding to ≈300-800 lung cancer cases/year. Conclusion. These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even in a low exposed general population. Health policy interventions are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1874. doi:10.1158/1538-7445.AM2011-1874
Cancer Research, 2014
Background: Alcohol consumption is known to be associated with risk of developing several cancers... more Background: Alcohol consumption is known to be associated with risk of developing several cancers. It is unclear, however, whether alcohol consumption is a risk factor for lung cancer. The relationship between lung cancer and alcohol consumption is likely to be confounded by smoking. To minimize potential confounding by tobacco consumption, we conducted a pooled analysis to examine the association of alcohol consumption with lung cancer risk in a large sample of never-smokers. Methods: We pooled data from 22 case-control and cohort studies from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. We examined the association of average lifetime alcohol consumption (expressed as average grams per day intake) with lung cancer risk in never smokers using logistic regression to model categories of alcohol consumption (0<5g per day, 5<10g per day, 10<20g per day, 20<30g per day, 30<45g per day, 45+ g per day). To inv...
The Annals of occupational hygiene, Jan 15, 2015
The present study analysed the asbestos lung burden in necroscopic samples from 55 subjects free ... more The present study analysed the asbestos lung burden in necroscopic samples from 55 subjects free from asbestos-related diseases, collected between 2009 and 2011 in Milan, Italy. Multiple lung samples were analysed by light microscopy (asbestos bodies, AB) and EDXA-scanning electron microscopy (asbestos fibres and other inorganic fibres). Asbestos fibres were detected in 35 (63.6%) subjects, with a higher frequency for amphiboles than for chrysotile. Commercial (CA) and non-commercial amphiboles (NCA) were found in roughly similar frequencies. The estimated median value was 0.11 million fibres per gram of dry lung tissue (mf g(-1)) for all asbestos, 0.09 mf g(-1) for amphiboles. In 44 (80.0%) subjects no chrysotile fibres were detected. A negative relationship between asbestos mass-weighted fibre count and year of birth (and a corresponding positive increase with age) was observed for amphiboles [-4.15%, 95% confidence interval (CI) = -5.89 to -2.37], talc (-2.12%, 95% CI = -3.94 to ...
Giornale italiano di medicina del lavoro ed ergonomia
A cross-sectional multicenter european study has been carried out to evacuate the relations betwe... more A cross-sectional multicenter european study has been carried out to evacuate the relations between exposure to low level of benzene and biological markers of internal dose (t,t-MA, S-PMA) and early biological effect (DNA-SSB). The research has shown significantly increased levels (adjusted for smoking habits) of the urinary excretion of t,t-MA, S-PMA and DNA-SSB in petrochemical workers (mean benzene level = 5,694 micrograms/m3) but not in filling station attendants, traffic police officers, and bus drivers compared to referent workers. Dose-response relations were detected between benzene air levels, t,t-MA, S-PMA and DNA-SSB in petrochemical workers, with significantly increased levels of DNA-SSB detected for benzene exposure levels in the range 391-1,800 micrograms/m3 (0.12-0.58 ppm).
American Journal of Hematology, 2015
Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations i... more Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations in TMPRSS6 gene encoding Matriptase‐2, a negative regulator of hepcidin transcription. Up to now, 53 IRIDA patients from 35 families with different ethnic origins have been reported and 41 TMPRSS6 mutations have been identified. TMPRSS6 polymorphisms are more frequent than mutations, and have been associated with variation in iron and hematologic parameters. Our study evaluated their presence in 113 subjects with iron deficiency anemia (IDA) partially responsive to oral iron therapy and in 50 healthy blood donors. Thalassemic trait was diagnosed in 38 patients. Sequencing analysis of TMPRSS6 gene revealed that the frequency of several polymorphisms was markedly different between IDA subjects and controls. In particular, the V736A TMPRSS6 polymorphism was associated to moderately lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin levels, and in thalassemia carriers ...
Transplantation Proceedings, 2008
Rates of overall graft survival after liver retransplantation (RETX) are still 20% lower than tho... more Rates of overall graft survival after liver retransplantation (RETX) are still 20% lower than those after primary liver transplantation (TX). On the basis of previous mathematical approaches from other authors who tried to identify prognostic variables for survival and prognostic risk scores for liver RETX, we studied 12 categorical and 17 continuous variables from the donor, the recipient, and the surgical procedure, among patients who underwent liver retransplantation. Data were retrieved in a retrospective study over the last 12 years, in order to overcome the possible gap of other series that often included RETX performed many years ago. We considered 394 consecutive cadaveric liver TXs in adult patients, namely, 351 primary TXs and 43 RETXs. Using multivariate logistic regression, we calculated the following equation for 1-year risk of death for patients undergoing liver RETX: log(Odds) ϭ Ϫ4.81 ϩ 2.23 ϫ Recipient Sex ϩ 1.86 ϫ Donor Age ϩ 1.60 ϫ MELD Score (where: Recipient Sex: F ϭ 0, M ϭ 1; Donor Age (years): Ͻ40 ϭ 0, 40-59 ϭ 1; 60ϩ ϭ 2; MELD Score: Ͻ26 ϭ 0, 26ϩ ϭ 1). With this formula, we built a decision tree to predict the individual risk of death based on the subject's profile. Keeping in mind that mathematical models can only help our decisional process and are not conclusive, our data needs to be validated on a larger scale. authors 3 speak about the possibility of futile transplantations. To overcome the problem of futile RETXs, some authors 4-7 have sought to identify patients with best chance From the Unità Operativa Chirurgia Generale e Trapianti di Fegato (U.
PLoS ONE, 2012
This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 ad... more This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 adult patients who received 2 grafts, 16 who received 3 grafts, and one who received 4 grafts over a 11 yr period. There was no statistically significant difference in graft survival after the first or the second RET (52, 40, and 29% vs 44, 36, and 18% at 1,5,and 10 yr, respectively: Log-Rank test, p = 0.30). Survivals at 1, 5, and 10 years of patients who underwent 2 (n = 151) or 3 (n = 15) RETs, were 65, 48,and 39% vs 59, 44, and 30%, respectively (p = 0.59). Multivariate analysis of survival showed that only the type of graft (whole vs reduced) was associated with a statistically significant difference (HR = 3.77, Wald test p = 0. 05); the donor age appeared to be a relevant factor as well, although the difference was not statistically significant (HR = 1.91, Wald test p = 0.08). Though late RETs have better results on long term survival relative to early RETs, no statistically significant difference can be found in early results, till three years after RET. Considering late first RETs (interval.30 days from previous transplantation) with whole grafts the difference in graft survival in RETs due to HCV recurrence (n = 17) was not significantly different from RETs due to other causes (n = 53) (65-58 and 31% vs 66-57 and 28% respectively at 1-5 and 10 years, p = 0.66).
PLoS ONE, 2011
There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of pap... more There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-yearretrospective study.
PLoS ONE, 2013
Background: De novo tumors (DNT) after liver transplantation (LT) represent a growing concern. Pa... more Background: De novo tumors (DNT) after liver transplantation (LT) represent a growing concern. Patients and Methods: We analyzed the incidence of DNT, type, time of onset, risk factors and mortality (as of 2010) in 494 adult patients transplanted in the last 26 years (1983-2009). Results: DNT occurred in 41 (8.3%) of the patients. The Standardized Incidence Ratio (SIR) compared with the Italian population was 1.8. There was a higher incidence in males (SIR 2.0), an expected extremely high rate of Kaposi's sarcoma (SIR 127.95) and unexpected higher rates of tumors of the bladder in males (SIR 3.3). The incidence of DNT was higher within the first two years of LT (SIR 2.7) for Kaposi's sarcoma (SIR 393.3) and after 10 years (SIR 1.7) for bladder tumors (SIR 10.6). Multivariate analysis identified alcoholic cirrhosis (HR = 3.0, 95% CI = 1.2-7.8) and sclerosing cholangitis (HR = 3.5, 95% CI = 1.1-11.3) in the recipient as main risk factors for the occurrence of DNT. Conclusions: Surveillance protocols for DNT must be specifically oriented to patients transplanted for alcoholic cirrhosis and sclerosing cholangitis. They should focus on early detection of Kaposi's sarcomas, and more remarkably, on late development bladder tumors in men after LT.
Occupational and Environmental Medicine, 2011
International Journal of Environmental Research and Public Health, Mar 13, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Benzene is a human carcinogen and a ubiquitous pollutant of outdoor and indoor air. For the defin... more Benzene is a human carcinogen and a ubiquitous pollutant of outdoor and indoor air. For the definition of exposure to low benzene level, and for the evaluation of health risk posed by this exposure, the identification of suitable, specific and sensible biological markers is needed. This research compared the capability to discriminate the exposure of three biomarkers of benzene: t,t-muconic acid, and S-phenylmercapturic acid and urinary benzene. Gasoline filling attendants (N = 78), urban policeman (N = 77) e and subjects working in urban environment, designed as controls (N = 58) were recruited for the study. Air and urine samples (pre and end shift) were collected for each subject. Smoking habit was investigated by the use of a questionnaire and by determination of urinary cotinine. This study was part of a larger European investigation on human exposure to low level of benzene and its potential effects. Median personal exposure to benzene during the work shift in filling attendants, urban policeman and controls was 61 (44-478), 22 (9-316) and 6 (2-115) µg/m3, respectively. Significant differences were found among groups. End-shift t,t-muconic acid was 73 (5-518), 129 (5-909) and 40 (5-1089) µg/L. End-shift S-phenylmercapturic acid was 6.6 (0.2-25), 5.9 (0.2-14) and 5.0 (0.2-14) µg/L. End-shift urinary benzene was 603 (42-5111), 220 (25-4246) and 154 (15-4615) ng/L. A significant correlation was found between urinary benzene, but not t,t-muconic acid or S-phenylmercapturic acid, and personal exposure to benzene. All the investigated biomarkes were strongly influenced by cigarette smoking that resulted an important source of personal exposure to benzene, and whose importance could overcome that of the occupational exposure. The comparison among t,tmuconic acid, S-phenylmercapturic acid and urinary benzene showed that, in the investigated range of exposure, only urinary benzene was useful to discriminate the airborne exposure.
Annals of Work Exposures and Health, Feb 25, 2022
In occupational epidemiology, job coding is an important—but time-consuming—step in assigning exp... more In occupational epidemiology, job coding is an important—but time-consuming—step in assigning exposure. We implemented a tool (i.e. a crosswalk) to translate occupation codes from the Italian (ISTAT-CIP-91, n = 6319 five-digit job codes) to the International Standard Classification of Occupations (ISCO-68, n = 1881 five-digit job codes). The former is currently used in Italy for various purposes (e.g. in the National Mesothelioma Registry). The latter has been used in several studies on occupational cancers because it facilitates communication of results to the scientific community and, most importantly, because some job exposure matrices (JEMs) are based on international codes. Three authors created a table containing the crosswalk structure, providing an interpretation for each of the ISTAT-CIP-91 codes job descriptions and then manually recoding them according to ISCO-68. Two other authors independently revised it. The performance of the final version was assessed by comparison with results obtained by manual ISCO-68 coding performed in two previous case-control studies on asbestos and mesothelioma. More specifically, the automatically obtained ISCO-68 codes were merged with a JEM (DOM-JEM). The resulting individual asbestos exposure estimates (ever versus never exposed) were compared to those originally obtained (using the same DOM-JEM) from manual translation of ISTAT-CIP-91 to ISCO-68 (considered as the ‘gold standard’). In the first study, among 159 peritoneal mesothelioma cases (400 job codes), Cohen’s kappa was 0.91, sensitivity 0.95, and specificity 0.96. In the second study, among 716 pleural mesothelioma cases and controls (4400 job codes) kappa was 0.86, sensitivity 0.94, and specificity 0.91. Performance was better among in women. For men, performance was lower among cases than among controls (kappa 0.70, sensitivity 0.95, specificity 0.72 versus kappa 0.87, sensitivity 0.97, and specificity 0.92). In conclusion, the proposed tool allowed a rapid translation of thousands of job codes with good to excellent accuracy. The table containing ISTAT-CIP-91 codes and job descriptions and the corresponding ISCO-68 codes and job descriptions is made publicly available and can be freely used for epidemiological analyses in Italy and international collaborations.
American Journal of Transplantation, Jul 1, 2020
International Journal of Environmental Research and Public Health, 2022
The PRIMATE study is an Italian translational research project, which aims to identify personaliz... more The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational...
Cancer Epidemiology, 2019
Background: There is inadequate evidence to determine whether there is an effect of alcohol consu... more Background: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. Methods: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. Results: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This Jshaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). Conclusions: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.
International journal of cancer, May 24, 2017
It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship... more It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversel...
British Journal of Haematology, 2016
Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the ... more Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the pathogenetic mechanism is not clear and data are contradictory, probably because of study heterogeneity and the multifactorial nature of the pathogenesis. We retrospectively analysed 73 adult TM patients to evaluate the prevalence of pulmonary dysfunction in adult TM and investigate relationships with iron load. All patients underwent body plethysmography and carbon monoxide diffusion (DLCO) was assessed in 63, in addition to blood tests, echocardiogram and T2* myocardial and liver magnetic resonance imaging. Restrictive lung disease was present in 26 (35Á6%) patients. Serum ferritin levels were higher in patients with restrictive pattern (1526 lg/l vs. 975 lg/l, P = 0Á05). Restrictive lung disease did not correlate with cardiac or liver iron overload. However, considering only patients with serum ferritin >2500 lg/l, those with restrictive pattern also had heart (T2* 14Á28 AE 9Á99 ms vs. 31Á59 AE 7Á43 ms) and liver iron overload (LIC 16Á02 AE 8Á44 mg vs. 5Á02 AE 2Á69 mg Fe/g dry weight) compared to those without restrictive pattern. Twenty-five patients (39Á7%) had decreased DLCO. No correlation was observed with iron parameters. In our data restrictive pattern was predominant; we observed a relationship with serum ferritin levels suggesting that iron, particularly its chronic effect, could play a role in the pathogenesis of pulmonary disease.
Cancer Research, 2011
Background. Exposure to occupational carcinogens is an important preventable cause of lung cancer... more Background. Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. Methods. We estimated lung cancer risk associated with occupational carcinogens using a new validated job-exposure matrix (JEM), in the Environment And Genetics in Lung cancer Etiology (EAGLE) study, a large (2100 cases and 2120 controls) population-based case-control study conducted in Lombardy, Italy, between 2002-2005. The JEM translated lifetime work-histories coded into standard job-titles into never, low, and high exposure levels for six known/suspected occupational lung carcinogens. We calculated odds ratios (OR) and 95% confidence intervals (CI) in men (1537 cases and 1617 controls), by multiple logistic regression, adjusted for potential confounders, e.g., tobacco smoking and co-exposure to JEM carcinogens. We estimated the Population Attributable Fraction (PAF) as impact measure. Results. Exposure to asbestos (OR=1.76, 95%CI=1.42 to 2.18), crystalline silica (OR=1.31, 95%CI=1.00 to 1.71), or nickel-chromium (OR=1.18, 95%CI=0.90 to 1.53) was associated with increased risk even at low exposures, with positive trends for intensity and duration. We found an excess risk for exposure to polycyclic aromatic hydrocarbons only among highly exposed workers (OR=1.64, 95%CI=0.99 to 2.70). The PAFs for any exposure to asbestos, crystalline silica and nickel-chromium were 18.1%, 5.7%, and 7.0%, respectively, corresponding to ≈300-800 lung cancer cases/year. Conclusion. These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even in a low exposed general population. Health policy interventions are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1874. doi:10.1158/1538-7445.AM2011-1874
Cancer Research, 2014
Background: Alcohol consumption is known to be associated with risk of developing several cancers... more Background: Alcohol consumption is known to be associated with risk of developing several cancers. It is unclear, however, whether alcohol consumption is a risk factor for lung cancer. The relationship between lung cancer and alcohol consumption is likely to be confounded by smoking. To minimize potential confounding by tobacco consumption, we conducted a pooled analysis to examine the association of alcohol consumption with lung cancer risk in a large sample of never-smokers. Methods: We pooled data from 22 case-control and cohort studies from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. We examined the association of average lifetime alcohol consumption (expressed as average grams per day intake) with lung cancer risk in never smokers using logistic regression to model categories of alcohol consumption (0<5g per day, 5<10g per day, 10<20g per day, 20<30g per day, 30<45g per day, 45+ g per day). To inv...
The Annals of occupational hygiene, Jan 15, 2015
The present study analysed the asbestos lung burden in necroscopic samples from 55 subjects free ... more The present study analysed the asbestos lung burden in necroscopic samples from 55 subjects free from asbestos-related diseases, collected between 2009 and 2011 in Milan, Italy. Multiple lung samples were analysed by light microscopy (asbestos bodies, AB) and EDXA-scanning electron microscopy (asbestos fibres and other inorganic fibres). Asbestos fibres were detected in 35 (63.6%) subjects, with a higher frequency for amphiboles than for chrysotile. Commercial (CA) and non-commercial amphiboles (NCA) were found in roughly similar frequencies. The estimated median value was 0.11 million fibres per gram of dry lung tissue (mf g(-1)) for all asbestos, 0.09 mf g(-1) for amphiboles. In 44 (80.0%) subjects no chrysotile fibres were detected. A negative relationship between asbestos mass-weighted fibre count and year of birth (and a corresponding positive increase with age) was observed for amphiboles [-4.15%, 95% confidence interval (CI) = -5.89 to -2.37], talc (-2.12%, 95% CI = -3.94 to ...
Giornale italiano di medicina del lavoro ed ergonomia
A cross-sectional multicenter european study has been carried out to evacuate the relations betwe... more A cross-sectional multicenter european study has been carried out to evacuate the relations between exposure to low level of benzene and biological markers of internal dose (t,t-MA, S-PMA) and early biological effect (DNA-SSB). The research has shown significantly increased levels (adjusted for smoking habits) of the urinary excretion of t,t-MA, S-PMA and DNA-SSB in petrochemical workers (mean benzene level = 5,694 micrograms/m3) but not in filling station attendants, traffic police officers, and bus drivers compared to referent workers. Dose-response relations were detected between benzene air levels, t,t-MA, S-PMA and DNA-SSB in petrochemical workers, with significantly increased levels of DNA-SSB detected for benzene exposure levels in the range 391-1,800 micrograms/m3 (0.12-0.58 ppm).
American Journal of Hematology, 2015
Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations i... more Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations in TMPRSS6 gene encoding Matriptase‐2, a negative regulator of hepcidin transcription. Up to now, 53 IRIDA patients from 35 families with different ethnic origins have been reported and 41 TMPRSS6 mutations have been identified. TMPRSS6 polymorphisms are more frequent than mutations, and have been associated with variation in iron and hematologic parameters. Our study evaluated their presence in 113 subjects with iron deficiency anemia (IDA) partially responsive to oral iron therapy and in 50 healthy blood donors. Thalassemic trait was diagnosed in 38 patients. Sequencing analysis of TMPRSS6 gene revealed that the frequency of several polymorphisms was markedly different between IDA subjects and controls. In particular, the V736A TMPRSS6 polymorphism was associated to moderately lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin levels, and in thalassemia carriers ...
Transplantation Proceedings, 2008
Rates of overall graft survival after liver retransplantation (RETX) are still 20% lower than tho... more Rates of overall graft survival after liver retransplantation (RETX) are still 20% lower than those after primary liver transplantation (TX). On the basis of previous mathematical approaches from other authors who tried to identify prognostic variables for survival and prognostic risk scores for liver RETX, we studied 12 categorical and 17 continuous variables from the donor, the recipient, and the surgical procedure, among patients who underwent liver retransplantation. Data were retrieved in a retrospective study over the last 12 years, in order to overcome the possible gap of other series that often included RETX performed many years ago. We considered 394 consecutive cadaveric liver TXs in adult patients, namely, 351 primary TXs and 43 RETXs. Using multivariate logistic regression, we calculated the following equation for 1-year risk of death for patients undergoing liver RETX: log(Odds) ϭ Ϫ4.81 ϩ 2.23 ϫ Recipient Sex ϩ 1.86 ϫ Donor Age ϩ 1.60 ϫ MELD Score (where: Recipient Sex: F ϭ 0, M ϭ 1; Donor Age (years): Ͻ40 ϭ 0, 40-59 ϭ 1; 60ϩ ϭ 2; MELD Score: Ͻ26 ϭ 0, 26ϩ ϭ 1). With this formula, we built a decision tree to predict the individual risk of death based on the subject's profile. Keeping in mind that mathematical models can only help our decisional process and are not conclusive, our data needs to be validated on a larger scale. authors 3 speak about the possibility of futile transplantations. To overcome the problem of futile RETXs, some authors 4-7 have sought to identify patients with best chance From the Unità Operativa Chirurgia Generale e Trapianti di Fegato (U.
PLoS ONE, 2012
This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 ad... more This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 adult patients who received 2 grafts, 16 who received 3 grafts, and one who received 4 grafts over a 11 yr period. There was no statistically significant difference in graft survival after the first or the second RET (52, 40, and 29% vs 44, 36, and 18% at 1,5,and 10 yr, respectively: Log-Rank test, p = 0.30). Survivals at 1, 5, and 10 years of patients who underwent 2 (n = 151) or 3 (n = 15) RETs, were 65, 48,and 39% vs 59, 44, and 30%, respectively (p = 0.59). Multivariate analysis of survival showed that only the type of graft (whole vs reduced) was associated with a statistically significant difference (HR = 3.77, Wald test p = 0. 05); the donor age appeared to be a relevant factor as well, although the difference was not statistically significant (HR = 1.91, Wald test p = 0.08). Though late RETs have better results on long term survival relative to early RETs, no statistically significant difference can be found in early results, till three years after RET. Considering late first RETs (interval.30 days from previous transplantation) with whole grafts the difference in graft survival in RETs due to HCV recurrence (n = 17) was not significantly different from RETs due to other causes (n = 53) (65-58 and 31% vs 66-57 and 28% respectively at 1-5 and 10 years, p = 0.66).
PLoS ONE, 2011
There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of pap... more There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-yearretrospective study.
PLoS ONE, 2013
Background: De novo tumors (DNT) after liver transplantation (LT) represent a growing concern. Pa... more Background: De novo tumors (DNT) after liver transplantation (LT) represent a growing concern. Patients and Methods: We analyzed the incidence of DNT, type, time of onset, risk factors and mortality (as of 2010) in 494 adult patients transplanted in the last 26 years (1983-2009). Results: DNT occurred in 41 (8.3%) of the patients. The Standardized Incidence Ratio (SIR) compared with the Italian population was 1.8. There was a higher incidence in males (SIR 2.0), an expected extremely high rate of Kaposi's sarcoma (SIR 127.95) and unexpected higher rates of tumors of the bladder in males (SIR 3.3). The incidence of DNT was higher within the first two years of LT (SIR 2.7) for Kaposi's sarcoma (SIR 393.3) and after 10 years (SIR 1.7) for bladder tumors (SIR 10.6). Multivariate analysis identified alcoholic cirrhosis (HR = 3.0, 95% CI = 1.2-7.8) and sclerosing cholangitis (HR = 3.5, 95% CI = 1.1-11.3) in the recipient as main risk factors for the occurrence of DNT. Conclusions: Surveillance protocols for DNT must be specifically oriented to patients transplanted for alcoholic cirrhosis and sclerosing cholangitis. They should focus on early detection of Kaposi's sarcomas, and more remarkably, on late development bladder tumors in men after LT.
Occupational and Environmental Medicine, 2011