Publications

Abstract Background: There are differences of opinion about the beneficial or detrimental effects of opium consumption on cardiovascular diseases (CVDs). So, we aimed to study the association between opium use and CVDs. Methods: We used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in IrAN (PERSIAN), with detailed, validated data on opium consumption and some other exposures. A total of 10,000 adults were enrolled in the study. Logistic regression models were used to assess the possible relationships of opium consumption with the prevalence of ischemic heart diseases (IHD) and myocardial infarction (MI). Results: In this study, 9990 participants in the baseline phase of the Rafsanjan adult cohort study were included according to their completed questionnaire. Among all participants, 870 and 296 individuals were found to suffer from IHD and MI, respectively. Opium consumption was found to be relatively high in the RCS participants, especially in men (men= 2150 and women= 228). Opium use was associated with a higher odds of IHD and MI, with the adjusted odds ratios (95% CI) of 1.51 (1.22-1.86) and 1.79 (1.31-2.45), respectively. Also, dose-response increases were observed with the highest odds ratios in the 4th quartile for MI and IHD ( p -values for trend < 0.001). Increased odds were observed for the two main methods of opium consumption, i.e. oral and smoking, but oral administration had higher odds ratio. Conclusions: Opium consumption is associated with the increased odds of both IHD and MI diseases.

The relationship between frequencies of consumption of selected indicator foods and the risk of thyroid cancer was investigated in a pooled analysis of 4 case-control studies conducted in 3 areas of northern Italy and the Swiss Canton of Vaud, on a total of 385 histologically confirmed cases of thyroid cancer and 798 controls in hospital for acute, non-neoplastic, non-hormone-related diseases. Cases tended to consume significantly more frequently a number of starchy foods: the odds ratio (OR) for the highest vs. lowest tertile was 1.8 for pasta or rice, 2.1 for bread, 1.6 for pastry and 2.0 for potatoes. ORs also tended to be above unity for several types of meat and significantly so for chicken and poultry, cooked ham, salami and sausages. Raw ham and fish were significantly protective (OR = 0.7 in the highest tertile for both). Significant direct associations were observed with cheese (OR = 1.4 for the highest tertile), butter (OR = 2.1) and oils other than olive (OR = 1.6). The risk estimates were below unity for most types of vegetables and fruits, and the inverse trends were significantly for carrots (OR = 0.6 for the highest tertile), green salad (OR = 0.6) and citrus fruits (OR = 0.7). No association was observed with alcohol intake. These results were consistent and reproducible across various study centers.

<p>DLBCL cases included in the study.</p>

The purpose of our study was to investigate the relation in between physical activity in different periods of life at work and in leisure-time and prostate cancer risk. We conducted a case-control study on prostate cancer in Italy between 1991 and 2002, which included 1,294 incident cases of histologically confirmed prostate cancer below 75 years of age and 1,451 controls, who were admitted to hospital for acute nonneoplastic conditions. Odds ratios (OR) of prostate cancer according to physical activity in different periods of life were obtained by unconditional multiple logistic regression models, including terms for age, study centre, education, social class, body mass index, energy intake, family history and other selected covariates. Compared to the lowest level of occupational physical activity, the multivariate ORs for prostate cancer for the highest level were 0.94 (95% confidence interval, CI, 0.75-1.17) at age 15-19, 0.78 (95% CI, 0.63-0.97) at age 30-39 and 0.75 (95% CI, 0.61-0.93) at age 50-59. A significant inverse trend in risk was found for activity at work at ages 30-39 and 50-59. The inverse associations were consistent in strata of age at diagnosis, body mass index, education and social class. No significant association was found for leisure-time physical activity. The inverse association between occupational physical activity and prostate cancer risk may reflect favorable hormonal correlates of physical activity, but residual confounding by socioeconomic covariates cannot be excluded.

Abstract Recent screening trials indicate that low-dose computed tomography (LDCT) reduces lung-cancer mortality in high risk subjects. However, high false positive rates, costs and potential harms highlight the need for complementary biomarkers. MicroRNAs (miRNAs) are tissue and disease specific molecules, actively released by cells in the circulatory system, which are associated with protein complexes and/or packaged in exosomes and microvesicles. Circulating miRNAs are rather stable and easily detectable in body fluids suggesting the possibility of using miRNAs as a new promising class of biomarkers. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) of a non-invasive plasma miRNA signature classifier (MSC) to identify lung cancer occurrence and mortality was retrospectively evaluated in samples prospectively collected from smokers within the randomized Multicentre Italian Lung Detection (MILD) trial. Plasma samples from 939 subjects including 69 lung cancer patients and 870 disease-free individuals were analyzed using a Real-Time quantitative PCR (qRT-PCR) based assay for MSC. Combined sensitivity and specificity of plasma MSC and LDCT were assessed in a blinded validation study. MSC correctly identified patients with lung cancer at 87% sensitivity, 81% specificity, and 99% NPV, and 18 of 19 lung cancer deaths at 95% sensitivity 81% specificity, and 99.86% NPV. MSC identified 43 of 49 (88%) LDCT-detected cancers, 8 of 9 (89%) interval cancers in the LDCT arm, and 9 of 11 (82%) cancers in the observational arm. Diagnostic performance of MSC was confirmed by time dependency analysis. MSC fell to negative after lung cancer resection in 16 of 22 evaluable subjects. In lung cancer patients, there was a trend in mortality across levels of MSC (p=0.0336) and survival rate significantly differed according to MSC in all subjects (X21=49.53, p<0.0001). Combination of MSC and LDCT resulted in a 5-fold reduction of LDCT false positive rate. This large validation study highlights the clinical diagnostic and prognostic value of plasma MSC for lung cancer screening in high-risk populations. The combined use of LDCT and MSC could reduce the false positive rate of LDCT improving the efficacy of lung cancer screening. Citation Format: Mattia Boeri, Carla Verri, Gabriella Sozzi, Luca Roz, Davide Conte, Paola Suatoni, Alfonso Marchiano, Carlo La Vecchia, Marta Rossi, Francesca Bravi, Eva Negri, Nicola Sverzellati, Ugo Pastorino. Clinical utility of a plasma microRNA biomarker within lung cancer screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 871. doi:10.1158/1538-7445.AM2014-871

The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints.

Management of PM varied widely in clinical practice, and significant predictors of treatment were younger age and recent diagnosis, though a high proportion of patients were not treated. Patients were treated in various hospitals, indicating the importance of concentrating serious rare neoplasms in Comprehensive Cancer Centers (as recognized by the Italian Health Ministry).