Plasma microRNA ratios associated with breast cancer detection in a nested case-control study from a mammography screening cohort.

Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case-control study was conducted within the ANDROMEDA cohort (women of age 46-67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted.Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538).

Promoting healthy lifestyle habits among participants in cancer screening programs: Results of the randomized controlled Sti.Vi study.

Background: Unhealthy diets, physical inactivity, alcohol and tobacco consumption are among the leading risk factors for non-communicable diseases. It is estimated that around 40% of cancers could be prevented by adopting healthy lifestyles. Design and methods: The Stili di Vita (Sti.Vi) study was a randomized study for assessing the impact of healthy lifestyle interventions on anthropometric measures, metabolic parameters, and health outcomes among participants of cancer screening programs in Turin (Italy). Eligible women aged 50-54 years, invited to biennial mammography screening, and 58-years-old men and women, invited to a once-only sigmoidoscopy for colorectal cancer (CRC) screening were randomly allocated to Diet group (DG), Physical Activity group (PAG), Physical Activity plus Diet group (PADG), or control group (CG). Physical and eating habits, metabolic and anthropometric measurements, repeatedly collected, were the study outcomes. The active intervention, offered to participants assigned to the DG, PAG, and PADG arms, consisted of a basic module and an advanced module. The effect of the interventions was estimated through logistic regression or a difference in differences approach. A multiple imputation procedure was implemented to deal with missing values and q-values have been calculated in the presence of multiple hypothesis testing. Results: Out of the 8442 screened attendees, 1270 signed informed consent, while 1125 participants accomplished the baseline visit. Participants were equally distributed across the four treatments as following: 273 (24.3%) in DG, 288 (25.6%) in the PAG, 283 (25.1%) in PADG, and 281 (25%) in the CG. Participants assigned to DG or PADG increased their consumption of whole grains (OR = 1.77, 95% CI: 1.20-2.60 and OR = 1.55, 95% CI: 1.06-2.27, respectively) and legumes (OR = 1.77, 95% CI: 1.12-2.79 and OR = 2.24, 95% CI: 1.41-3.57, respectively), with respect to CG. The participants randomized to DG reduced processed meat and increased fruit consumption (OR = 2.57, 95% CI: 1.76-3.76 and OR = 2.38, 95% CI: 1.12-5.06, respectively). The effects were more evident in the CRC screening subgroup. No relevant difference was observed between PAG and CG. No impact was observed on physical activity habits. Conclusions: Our findings suggest that active interventions can increase awareness and induce diet changes. However, participation rate and compliance to the courses was quite low, innovative strategies to enhance participants' retention are needed, with the ultimate goal of increasing awareness and inducing positive lifestyle changes.

Oncophone20 study: Patients' perception of telemedicine in the COVID-19 pandemic during follow-up visits for gynecological and breast cancers.

OBJECTIVE: To analyze oncological patients' perception of telemedicine during the COVID-19 pandemic. METHODS: A total of 345 women, of whom 267 experienced breast cancer and 78 experienced a gynecological cancer, were enrolled. Specific questionnaires about their experiences and feelings about telemedicine in the COVID-19 era were collected. RESULTS: In the breast group, "enhanced care" showed moderate positive perception (mean 4.40) among less-educated women that was slightly lower among better-educated women (mean 4.14) with a significant difference (P = 0.034). "satisfaction" had an opposite pattern: a mean of 3.99 for a lower level of education and 4.78 for a higher level of education, with a strong significant difference (P < 0.001). "privacy and discomfort" approached neutrality for less-educated women, while for higher-educated women the lower mean of 2.93 indicted a more positive perception (P = 0.007). In the pelvic group, younger women had a better perception towards telemedicine for "telemedicine as a substitution" (mean 3.68) compared to older women (mean 3.05). The privacy and discomfort subscale was in favor of better-educated women (mean 2.57) compared to less-educated women (mean 3.28; P = 0.042). CONCLUSION: Telemedicine was generally well accepted, not only among younger and higher-educated women but also by women needing intensive care, in both cancer groups.

Biomedical and health research: an analysis of country participation and research fields in the EU's Horizon 2020.

We analysed the Horizon 2020 project database, currently the European Union's (EU) largest framework programme for research and innovation-nearly 80 billion euros available over 7 years (2014-2020), to estimate the amount and type of EU-supported biomedical and health research and funding distribution among EU member states and non-European countries. Out of 20,877 projects as of 14th January 2019, a total of 4865 projects were classified as human health related. Ninety-four countries/territories worldwide participated in at least one biomedical project. The EU-15 original member states showed the highest participation as project leaders/partners and for acquired funding. Strong unequal funding distribution and participation between EU-15 and the 13 newest members-with EU-15 receiving about 87% of funding and EU-13 only 3%-have been evidenced. For both EU-15 and EU-13 we detected about 20% of projects involving the public and private sectors, according to Horizon 2020 guidelines. The largest percentage of projects was in the areas of biotechnological research (28.28%) and "basic research" (26.95%); these two sectors together accounted for 46.99% of the total funding assigned (7.9 billion euros). Research in neurosciences and neurological diseases appeared to be an increasing study area. Neurological and mental diseases covered about 21% of projects. Epidemiological studies accounted for about 5% of the total projects and for 14% of funding. Strong correlations were shown by indicators of financial and scientific capacity to identify success rates in obtaining EU funding, making the gap between countries with strong and weak research infrastructures difficult to overcome.

The ANDROMEDA prospective cohort study: predictive value of combined criteria to tailor breast cancer screening and new opportunities from circulating markers: study protocol.

BACKGROUND: In recent years growing interest has been posed on alternative ways to screen women for breast cancer involving different imaging techniques or adjusting screening interval by breast cancer risk estimates. A new research area is studying circulating microRNAs as molecular biomarkers potentially useful for non invasive early detection together with the analysis of single-nucleotide polymorphisms (SNPs). The Andromeda study is a prospective cohort study on women attending breast cancer screening in a northern Italian area. The aims of the study are: 1) to define appropriate women risk-based stratifications for personalized screening considering different factors (reproductive, family and biopsy history, breast density, lifestyle habits); 2) to evaluate the diagnostic accuracy of selected circulating microRNAs in a case-control study nested within the above mentioned cohort. METHODS: About 21,000 women aged 46-67 years compliant to screening mammography are expected to be enrolled. At enrolment, information on well-known breast cancer risk factors and life-styles habits are collected through self-admistered questionnaires. Information on breast density and anthropometric measurements (height, weight, body composition, and waist circumference) are recorded. In addition, women are requested to provide a blood sample for serum, plasma and buffy-coat storing for subsequent molecular analyses within the nested case-control study. This investigation will be performed on approximately 233 cases (screen-detected) and 699 matched controls to evaluate SNPs and circulating microRNAs. The whole study will last three years and the cohort will be followed up for ten years to observe the onset of new breast cancer cases. DISCUSSION: Nowadays women undergo the same screening protocol, independently of their breast density and their individual risk to develop breast cancer. New criteria to better stratify women in risk groups could enable the screening strategies to target high-risk women while reducing interventions in those at low-risk. In this frame the present study will contribute in identifying the feasibility and impact of implementing personalized breast cancer screening. TRIAL REGISTRATION: NCT02618538 (retrospectively registered on 27-11-2015.).

Inequalities in cervical cancer screening utilisation and results: A comparison between Italian natives and immigrants from disadvantaged countries.

Cervical cancer screening underutilisation is documented among immigrants from poor countries and it is associated to an augmented risk for severe lesions. In a cohort of 1,410,364 Italian women and 200,491 immigrants from poor countries differences in screening participation and results were investigated. Participation rate was lower for immigrants than for Italians: 43.98% versus 48.59% (chi(1): p<0.001). This gap increased with age (ptrend<0.0001). Some socio-demographic factors negatively influenced immigrants' participation. Illiteracy (OR=0.75) versus secondary school, being single (OR=0.71) versus attached, first screens (OR=0.67) versus subsequent ones. Although the interaction between educational and professional levels showed that graduated immigrant women conducting an intellectual job have a higher inclination towards screening than their Italian peers (OR=1.43 vs OR=1.04). The Standardised Detection Ratio (SDR) suggested a frequency of severe lesions nearly double among immigrants in first screens (SDR=1.94; 95% CI: 1.82-2.08) and even higher (SDR=2.53; 95% CI: 2.35-2.73) for Central/Eastern Europeans. Multi-component interventions involving both patients and providers offer the greatest potential to increase cervical cancer screening uptake within foreign-born populations. So immigrant-specific interventions are needed for some immigrant groups, like Central/Eastern Europeans who are at higher risk of cervical lesions and, together with Asians and Africans, showed a poor attitude towards cancer prevention.

[Integrating cancer screening and primary prevention: a review]. / Esperienze di integrazione tra screening dei tumori e prevenzione primaria: una rassegna.

Cancer screening may represent an ideal setting for promoting healthy lifestyle. We conducted a literature review of intervention studies of primary prevention interventions implemented in the context of established screening programmes. We identified 11 trials, 3 of which conducted in Italy. A positive impact of these interventions in favouring the adoption of cancer protective dietary behaviours was observed in all studies. A limited impact was reported for physical activity, while no effect could be observed for interventions aimed to promote smoking cessation. Long term maintenance of the observed behavioural changes and the sustainability overtime of these interventions within population-based programmes should be assessed. To enhance their effectiveness, these health education programmes should include multiple strategies, integrating and combining models of individual, social, and environmental change.

[Introduction of a centralised system (Service) for collecting clinical data in cancer screening programmes in Piedmont (Northern Italy): a pre-post assessment of a hub&spoke model]. / L'introduzione di un sistema centralizzato (Service) per la raccolta dei dati clinici negli screening oncologici in Piemonte: valutazione pre-post di un modello hub&spoke.

OBJECTIVES: evaluation of a centralised collection of clinical data (Service) within cancer screening programmes in Piedmont based on a hub&spoke model and its impact on process indicators. DESIGN: assessment of an organisational intervention, through a non-controlled pre-post design. SETTING AND PARTICIPANTS: organised screening programmes within the Piedmont Region, divided into 9 departments. MAIN OUTCOME MEASURES: clinical data (extracted from medical charts for mammography screening and from excision histology reports for cervical screening) obtained through the Service were quantified and their completeness was assessed. The Service impact on the detection rate (DR) was evaluated, comparing the DR pre- (2005-2008) and post-Service (2009- 2012) within breast screening; the DR was computed through histological diagnosis made during colposcopy (pre-Service method) or through the worst diagnosis between the latter and that reported from excision histology (post-Service method) within cervical screening (data available for department 1, year 2013). Some hints on human resources employed in pre- and post-Service periods were reported. RESULTS: within mammography screening, the Service obtained 53.1% of extra-department medical charts and 45.8% of extra-region ones; the percentage of missing diagnoses changed from 5.5% (pre- Service) to 3.7% (post-Service). The age standardised DR for malignant tumours in the post-Service period is 1.3 times the DR of the pre-Service period per 1,000 screening tests. Within cervical screening, 51.7% of histological reports was recorded. Crude DR for high-grade lesions changed from 3.9 (pre-Service) to 4.7 (post-Service) per 1,000 screened women. The system centralisation did not imply an increase in the dedicated personnel. CONCLUSION: the Service is an operational core which coordinates the collection of clinical data, impacting on process indicators without an increase in human resources at departmental level.

HPV prevalence and risk of pre-cancer and cancer in regular immigrants in Italy: results from HPV DNA test-based screening pilot programs.

UNLABELLED: ᅟ: Immigrants from low- and medium-income countries have a higher risk of cervical cancer due both to barriers in access to screening and to higher human papillomavirus (HPV) prevalence. In the near future many screening programmes in industrialised countries will replace Pap test with HPV as primary test. In order to plan future interventions, it is essential to understand how the HPV screening performs in immigrant women. METHODS: We conducted a survey on the main performance indicators from some of the HPV DNA-based pilot programmes in Italy, comparing regular immigrant women, identified as women resident in Italy who were born abroad, with women who were born in Italy. All the programmes applied the same protocol, with HPV as stand-alone test starting for women of 25 or 35 to 64 years of age. Cytology triage is performed for positive women; those ASC-US or more severe are referred directly to colposcopy; negative women are referred to repeat HPV after one year. RESULTS: Overall, 162,829 women were invited, of whom 22,814 were born abroad. Participation was higher for Italy-born than born abroad (52.2% vs. 43.6%), particularly for women over 45 years. HPV positivity rate was higher in immigrants: 7.8% vs. 6.1%, age-adjusted Relative Risk (age-adj RR) 1.18, 95% confidence interval (95% CI) 1.13-1.22. The proportion of women with positive cytology triage was similar in the two groups (42%). Cervical Intraepithelial Neoplasia (CIN) grade 2 or more severe detection rate was higher for born abroad (age-adj RR 1.65, 95% CI 1.45-1.89). The difference was stronger when considering only CIN3 or more severe (age-adj RR 2.29, 95% CI 1.90-2.75). Both HPV positivity and CIN2 or more severe detection rate had a different age curve in born abroad compared with Italy-born: in the former, the risk was almost flat, while in the latter it declined rapidly with age. CONCLUSION: Compliance with HPV screening is lower for migrant women, who are affected by higher HPV positivity and CIN3 cancer detection rates.

Population health and status of epidemiology in Western European, Balkan and Baltic countries.

BACKGROUND: This article is part of a series commissioned by the International Epidemiological Association, aimed at describing population health and epidemiological resources in the six World Health Organization (WHO) regions. It covers 32 of the 53 WHO European countries, namely the Western European countries, the Balkan countries and the Baltic countries. METHODS: The burdens of mortality and morbidity and the patterns of risk factors and inequalities have been reviewed in order to identify health priorities and challenges. Literature and internet searches were conducted to stock-take epidemiological teaching, research activities, funding and scientific productivity. FINDINGS: These countries have among the highest life expectancies worldwide. However, within- and between-country inequalities persist, which are largely due to inequalities in distribution of main health determinants. There is a long tradition of epidemiological research and teaching in most countries, in particular in the Western European countries. Cross-national networks and collaborations are increasing through the support of the European Union which fosters procedures to standardize educational systems across Europe and provides funding for epidemiological research through framework programmes. The number of Medline-indexed epidemiological research publications per year led by Western European countries has been increasing. The countries accounts for nearly a third of the global epidemiological publication. CONCLUSIONS: Although population health has improved considerably overall, persistent within- and between-country inequalities continue to challenge national and European health institutions. More research, policy and action on the social determinants of health are required in the region. Epidemiological training, research and workforce in the Baltic and Balkan countries should be strengthened. European epidemiologists can play pivotal roles and must influence legislation concerning production and access to high-quality data.

[Epidemiologic research in Italy: a comparison with the rest of Europe and the United States]. / La ricerca epidemiologica in Italia: un confronto con il resto d'Europa e gli Stati Uniti.

OBJECTIVE: the study describes the burden of the Italian epidemiological research compared to that of the other 26 countries belonging to the European Union and to that of the United States, in the period 2007-2009. This is accomplished for both scientific published papers and grants obtained. DESIGN AND SETTING: the searching in Medline database (February 2010) was done through complex search strings based on keywords corresponding to the various epidemiological research fields; grants were identified through 7th Framework Program (FP7), among those funded within February 2010. MAIN OUTCOME MEASURES: proportions of epidemiological papers published by researchers of the different countries and total number and amount of granted research projects for each European country. RESULTS: in the period 2007-2009 epidemiological papers by Italian researchers account for about one-eighth of the total European production. This makes of Italy the second country in production, after the United Kingdom. Moreover, Italy is involved in 51.3%of the 374 studies granted through FP7: at least one Italian research body participates in 154 projects and Italian researches co-ordinate 38 projects. CONCLUSION: in Italy biomedical and epidemiological research is in a developing phase despite the difficulties due to the decrease in the amount of funds available.Moreover, Italian research is carried out mainly by public bodies and by Universities, even if a deeper involvement of local health authorities and regional agencies is desirable.

Genetic polymorphisms of CYP17A1, vitamin D receptor and androgen receptor in Italian heredo-familial and sporadic prostate cancers.

BACKGROUND: Searching for genetic and environmental factors predisposing to prostate cancer, common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the number of CAG repeats from AR were investigated in Italian heredo-familial prostate cancer (HFPC) patients controlled for dietary intake and life style habits. METHODS: We evaluated differences between HFPC and sporadic cancers, in the pattern of common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the CAG repeat from AR, controlling for dietary intake and lifestyle habits in a regionwide population. Ninety-five patients with HFPC were identified and 378 sporadic prostate cancers were randomly selected as controls. Dietary intake and lifestyle habits were determined through self-administered questionnaires in all patients. Genotyping of polymorphisms for CYP17A1, CYP19A1, VDR, and the CAG repeat from AR was carried out using pyrosequencing. RESULTS: HFPC cases were significantly younger than controls, whereas similar proportions of localized tumours, favourable histology, and abnormal prostate serum antigen levels (4-19 ng/ml) were detected in the two groups. A statistically evident gene-gene interaction was found: a 5-fold higher probability [odds ratio (OR)=4.83; 95% confidence interval (CI): 1.37-17.02] of HFPC was observed in the subgroup profiling VDR1 T/T genotypes coupled with VDR2 T/T genotype. Among nutrients, an increase in HFPC risk (OR=3.14; 95% CI: 1.12-8.81) was found only for zinc, when associated with the VDR2 T/T genotype. CONCLUSIONS: Significant evidence for positive interactions between VDR1 and VDR2 genotypes was demonstrated, suggesting that high-risk multigenic polymorphism profiles could variously sustain HFPC tumorigenesis.