Search

BackgroundNight 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 methodsWe 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.ResultsEver 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.ConclusionsWe 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.

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.

BackgroundThe 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. MethodsThe 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. ResultsVery 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 x 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. ConclusionsOur findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.

IntroductionIn 2010, the International Agency for Research on Cancer (IARC) classified ‘Shiftwork that involves circadian disruption’ as a probable human carcinogen (group 2A), based on limited evidence from epidemiological studies and sufficient evidence from experimental animal studies. The epidemiological results were consistent for breast cancer. More recent publications suggested an increase in risk for ovarian and endometrial cancer, prostate cancer, and colorectal cancer.Sleep deprivation is common in shift workers, and it leads to disruption of the transcription of genes implicated in the regulation of the immune response.ObjectivesAs depression of the immune system is a known risk factor for lymphomas, we explored the association between risk of lymphoma subtypes and nightshift work with a case-control study design.Materials and methodsBased on the lifetime occupational history available for 323 cases and 463 controls who participated in a case-control study on lymphoma etiology conducted in Sardinia (Italy) in 1998–2006, expert occupational physicians assessed nightshift work for each job entry of each study subject. We calculated risk of major lymphoma subtypes, namely diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, multiple myeloma and Hodgkin lymphoma, associated with cumulative days of nightshift work with unconditional logistic regression, adjusting by age, gender, and education.ResultsNone of the lymphoma subtypes we investigated showed an association with lifetime cumulative days of nightshift work. Contrary to our expectation, risk of all lymphomas combined tended to decrease with cumulative days of nightshift work.ConclusionsFurther studies are warranted to investigate in more detail whether sleep deprivation resulting from nightshift work might be implicated in lymphomagenesis. Future investigations should include information on the chronotype of study subjects, the specific shift rotation schedule applied in each workplace, usual hours of sleep per day, and occurrence of daytime sleepiness.

Objective Dioxin, a known risk factor for lymphoma, and numerous other xenobiotics, induce their own metabolism by initially activating the aryl hydrocarbon receptor (AhR). We used the serum samples of participants to the multicentre Italian study on gene-environment interactions in lymphoma aetiology (ITGxE) to explore AhR activation as an intermediate step in dioxin-induced risk of lymphoma, and particularly B-cell lymphoma subtypes. Methods Overall, serum samples of 343 lymphoma cases and 1899 population and hospital controls from five Italian areas (Florence, Bari, Perugia, Novara, and central and southern Sardinia) were available for study. A 50 microliter serum aliquot of each study participant potentially carrying the AhR activator, was added to HepG2 cells, transfected with specific reporter systems including the DRE specific AhR activating sequence upstream to the luciferase reported gene. The intensity of light generated by the Dual-Luciferase Assay, captured with a luminometer, is directly correlated with the concentration and potency of the inducing xenobiotic. Risk of lymphoma overall and by its major B-cell specific subtypes associated with AhR activation positivity as a binary outcome was calculated using an unconditional logistic regression model adjusted by age and gender. Results Among the B-cell lymphoma subtypes, there was a significant two-fold excess risk for follicular lymphoma (OR = 2.0, 95% CI: 1.0, 4.0) and chronic lymphocytic leukaemia (OR = 2.3, 95% CI: 1.0, 5.0). No increase in risk associated with AhR positivity was observed for the other B-cell lymphoma subtypes we tested, namely diffuse large B-cell lymphoma, and multiple myeloma, nor for Hodgkin lymphoma. Conclusions Our results show that the Dual-Luciferase Assay is a reliable and inexpensive test to detect AhR activation and its role in lymphomagenesis.

This study included 304 women, 128 Screen Detected (SD) e 176 non Screen Detected (NSD), aged 50-69, living in the ex-local health authorities (LHAs) 13 and 14, hospitalized for breast cancer or related chemotherapy or radiation treatments in 2003-2004. Some variables were detected from medical records in order to evaluate the local screening program. The results confirm that a prevention activity allows a rapid identification of cancer and less invasive surgery procedures.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.

Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N -acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96–2.26) and in the entire population (OR=1.38; 95% CI=0.93–2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the clonal expansion of malignant B cells. To predict the clinical course of the disease, the identification of diagnostic biomarkers is urgently needed. Aberrant methylation patterns may predict CLL development and its course, being very early changes during carcinogenesis. Our aim was to identify CLL specific methylation patterns and to evaluate whether methylation aberrations in selected genes are associated with changes in gene expression. Here, by performing a genome-wide methylation analysis, we identified several CLL-specific methylation alterations. We focused on the most altered one, at a CpG island located in the body of SHANK1 gene, in our CLL cases compared to healthy controls. This methylation alteration was successfully validated in a larger cohort including 139 CLL and 20 control in silico samples. We also found a positive correlation between SHANK1 methylation level and absolute lymphocyte count, in particular CD19+ B cells, in CLL patients. Moreover, we were able to detect gains of methylation at SHANK1 in blood samples collected years prior to diagnosis. Overall, our results suggest methylation alteration at this SHANK1 CpG island as a biomarker for risk and diagnosis of CLL, and also in the personalized quantification of tumor aggressiveness.