Lifetime occupational and recreational physical activity and risk of lymphoma subtypes. Results from the European Epilymph case-control study.

Physical activity is known to convey protection against several cancers. However, results on the risk of lymphoma overall and its subtypes have been inconsistent. The aim of this study was to investigate occupational and recreational physical activity in relation to risk of lymphoma subtypes adjusting for established occupational risk factors. We applied standardized tools to assess energy expenditure at work and in recreational physical activities to the questionnaire information on lifetime work and exercise history in 1117 lymphoma cases, including Hodgkin lymphoma, and B-cell (including chronic lymphocytic leukemia, and multiple myeloma) and T-cell non-Hodgkin's lymphoma (NHL) subtypes, and 1207 controls who took part in the multicentre European EpiLymph case-control study. We calculated the risk of lymphoma (all subtypes), B-cell NHL and its most represented subtypes, and Hodgkin's lymphoma (all subtypes) associated with weekly average Metabolic Equivalent of Task (MET-hours/week) and cumulative MET-hours of lifetime recreational, occupational, and total physical activity, with unconditional logistic regression and polytomous regression analysis adjusting by age, centre, sex, education, body mass index, history of farm work and solvent use. We observed an inverse association of occupational, and total physical activity with risk of lymphoma (all subtypes), and B-cell non-Hodgkin's lymphoma among women, and an upward trend in risk of Hodgkin's lymphoma with recreational and total physical activity among men, for which we cannot exclude chance or bias. Our results suggest no effect of overall physical activity on risk of lymphoma and its subtypes.

Is a Good Sleep on Mosquito-Free Nights Worth the Risk of Lymphoma Associated with the Use of Household Insecticides? A Case-Control Study of Lymphoma Subtypes in Adults.

BACKGROUND: The evidence linking the use of household pesticides and the risk of lymphoma is scanty. METHODS: We explored the hypothesis in a population-based case-control study on lymphoma conducted in Sardinia, Italy, in 1998-2004, including 325 cases and 465 population controls and data on lifetime frequency, seasonality, and years of use of household insecticides and potential confounders. We calculated the risk of lymphoma (all subtypes) and its major subtypes associated with using household insecticides in three time windows (up to 1978, from 1979-2001, and 2002 onwards) with unconditional logistic regression adjusting by age, sex, education, and occupational exposure to pesticides. RESULTS: Household insecticides did not increase risk of lymphoma (all subtypes), Hodgkin's lymphoma, B-cell lymphoma, and the major B-cell lymphoma subtypes. The risk of multiple myeloma (MM) but not the other subtypes showed a non-significant upward trend (p = 0.203) with increasing quartiles of days of use in the time window when propoxur was the most popular household insecticide. CONCLUSIONS: Our results suggest no association between the household use of insecticides and the risk of lymphoma. Further studies are warranted to confirm or discard an association between MM risk and the use of propoxur.

Study of the DNA binding mechanism and in vitro activity against cancer cells of iron(III) and aluminium(III) kojic acid derivative complexes.

Metal ions have unique electrochemical and spectroscopical properties that cannot be attained by purely organic compounds. Most of the metal ions are toxic to humans, but paradoxically, metallodrugs are used in medicine as therapeutics and theranostics. Metallodrugs are eliminated in urine and faeces, and therefore release toxic metals and ligands into aquatic ecosystems, thereby raising concerns regarding environmental risks. The use of metallodrugs based on essential metal ions (i.e., iron, copper and zinc), instead of toxic ions, is a new alternative with minor hazards. Kojic acid is an Asperigillus oryzae metabolite of low toxicity used in the food and cosmetics industries. Its derivatives form stable complexes with iron(III) ions, which bind effectively to DNA and inhibit DNA polymerization. The iron(III)/S2 ligand complexes reduce in vitro colon carcinoma (Caco2) cell viability and significantly decrease the cell number. The kojic acid derivative complexes with iron(III) presented here are an alternative to the currently used platinum complexes in cancer therapy.

Incidence of non-Hodgkin's lymphoma among adults in Sardinia, Italy.

The causes of the peculiar time trend in the incidence of non-Hodgkin's lymphoma (NHL) in most parts of the world and of its geographic distribution are still unknown. We used the data base of 1974-2003 incident cases of hematological malignancies to explore the time trend of NHL incidence in the region of Sardinia, Italy, and we used Bayesian methods to plot the probability of NHL incidence by residential unit on the regional map. In 1974-2003, 4109 NHL cases were diagnosed among resident adults in Sardinia, with an incidence rate of 13.38 x 10-5 (95% CI 12.97-13.80). NHL incidence showed an upward trend along the study period with an average annual percent change (APC) of 4.94 (95% CI -5.39-16.4), which did not vary by gender or by age-group. Cancer registry data, covering part of the region starting from 1993, suggest that the increasing trend did not persist in the subsequent years. Areas with the highest probability of an excess incidence tended to cluster in the north-eastern part of the region and in two major urban centers, with the low incidence areas located in the south, confirming previous observations. Prevalence of viral infections, environmental and occupational exposures, or socio-economic deprivation would not explain the peculiar geographic distribution we observed. These findings provide convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants of NHL in the risk areas.

Time trend and Bayesian mapping of multiple myeloma incidence in Sardinia, Italy.

A few reports have described increasing trends and spatial distribution of multiple myeloma (MM). We used a validated database including the 1606 cases of MM diagnosed in Sardinia in 1974-2003 to explore its time trend, and we applied Bayesian methods to plot MM probability by administrative unit on the regional map. Over the 30 years of observation, the MM standardized incidence rate (standard world population, all ages) was 2.17 × 10-5 (95% CI 2.01-2.34), 2.29 (95% CI 2.06-2.52) among men, and 2.06 (95% CI 1.83-2.28) among women. MM incidence increased by 3.3%/year in 1974-2003, in both males and females, particularly among the elderly and in the high incidence areas. Areas at risk tended to cluster in the north-eastern part of the region. A higher proportion of elderly in the resident population, but not socioeconomic factors, nor livestock farming, was associated with higher incidence rates. The steep upward time trend and the spatial clustering of MM suggest interactions between genetic and environmental determinants that might be more efficiently investigated in the areas at risk.

Night shift work and lymphoma: results from an Italian multicentre case-control study.

BACKGROUND: Night shift work can disrupt circadian rhythm and cause chronic sleep deprivation, which might increase the risk of lymphoma through immunosuppression and oxidative stress. MATERIAL AND METHODS: We investigated the association between night shift work and risk of lymphoma subtypes in 867 incident cases and 774 controls, who participated in a multicentre Italian study between 2011 and 2017. Based on questionnaire information, occupational experts assessed the lifetime probability of night shift work, the total number of night shifts and years of night shift work among study participants. OR and 95% CI for lymphoma and its major subtypes associated with night shift work was calculated with logistic regression, adjusting by age, gender, education, study area, marital status and family history of haemolymphatic cancer. RESULTS: Ever working night shifts was associated with an increase in the risk of chronic lymphocytic leukaemia (CLL) (OR 1.9, 95% CI 1.14 to 3.32), which was highest after a 15-34 years latency. However, there was not a linear increase in risk by probability of exposure, years of night shift work, nor lifetime number of night shifts whether under rotating or permanent work schedules. Risk of lymphoma overall, B cell lymphoma (BCL), its major subtypes other than CLL, and other less prevalent BCL subtypes combined did not show an association. CONCLUSIONS: We found conflicting evidence of an association between night shift work and the risk of CLL. We did not observe an association with other lymphoma subtypes.

Occupational exposure to glyphosate and risk of lymphoma:results of an Italian multicenter case-control study.

BACKGROUND: The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy. METHODS: The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011-17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre. RESULTS: Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10- 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL. CONCLUSIONS: Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.

Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy.

BACKGROUND: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions. METHODS: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects. RESULTS: Although always below the European Union limit of 5 µg/m3, airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area (p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples (p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion. CONCLUSIONS: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study.

Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01-4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00-4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.

Gastrointestinal coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention, and management.

INTRODUCTION: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common. AREA COVERED: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission. EXPERT OPINION: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.

Haemolymphatic cancer among children in Sardinia, Italy: 1974-2003 incidence.

OBJECTIVES: To explore the time trend and geographical distribution of childhood leukaemia incidence over the territory of the Italian region of Sardinia. SETTING: All hospitals departments, diagnostic centres and social security agencies in Sardinia were regularly screened in 1974-2003 to identify, register and review the diagnoses of incident cases of haematological malignancies (HM). PARTICIPANTS: The whole child population aged 0-14 resident in Sardinia. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidence and time trend of childhood HM and childhood acute lymphoblastic leukaemia (ALL) over the study period, and use of Bayesian methods to plot the probability of areas with excess incidence on the regional map. RESULTS: Overall, 675 HM cases, including 378 ALL cases, occurred among children aged 0-14 years resident in Sardinia in 1974-2003, with an incidence rate of 6.97×10-5 (95% CI 6.47 to 7.51) and 3.85×10-5 (95% CI 3.48 to 4.26), respectively. Incidence of HM and ALL showed an upward trend along the study period especially among females. Three communes out of the 356 existing in 1974, namely Ittiri, Villa San Pietro and Carbonia, stand out as areas with excess incidence of HM and ALL in particular and another, Carloforte, for ALL only. CONCLUSIONS: Our results might serve as convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants in the areas at risk.

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study.

BACKGROUND: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels. METHODS: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education. RESULTS: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation. CONCLUSIONS: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.

Return to Work of Breast Cancer Survivors: Perspectives and Challenges for Occupational Physicians.

Breast cancer is one of the most common diseases worldwide, mainly affecting the female gender. Considering the increase of breast cancer incidence and the decrease of mortality due to news diagnostic and therapeutic tools, the return to work issue after treatment is going to be very common in the next years. Occupational physicians therefore need to face the return to work and the fitness for work of workers previously diagnosed with breast cancer with a sufficient cultural and technical background. In addition to individual characteristics preceding the diagnosis, clinical outcome, lifestyles and occupational variables are the most impactful factors on return to work that need to be taken into account. The aim of this work is to analyze these factors and discuss the central role of occupational physicians in the decision-making process of returning to work in breast cancer survivors.

Pulmonary Function and CT Scan Imaging at Low-Level Occupational Exposureto Asbestos.

Background: In spite of the reduced exposure level, and its ban in numerous countries, compensation claims for asbestos-related diseases are far from decreasing. Methods: We used retrospective exposure assessment techniques to explore respiratory function and a computerized tomography (CT) scan in relation to past asbestos exposure in 115 male workers retired from an acrylic and polyester fiber plant. Based, on detailed information on exposure circumstances, we reconstructed a cumulative exposure estimate for each patient. Results: Time-weighted average exposure in our study population was 0.24 fibers/ml (95% confidence inteval (CI) 0.19-0.29), and the average cumulative exposure was 4.51 fibers/mL-years (95% CI 3.95-5.07). Exposure was elevated among maintenance workers, compared to other jobs (p = 0.00001). Respiratory function parameters did not vary in relation to the exposure estimates, nor to CT scan results. Risk of interstitial fibrosis showed a significant upward trend (Wald test for trend = 2.62, p = 0.009) with cumulative exposure to asbestos; risk associated with 5.26 fibers/mL-years or more, was 8-fold (95% CI 1.18-54.5). Conclusions: Our results suggest that a CT scan can detect pleuro-parenchymal lung alterations at asbestos exposure levels lower than previously thought, in absence of respiratory impairment. Further studies are required to validate our techniques of retrospective assessment of asbestos exposure.