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BackgroundUK policy makers have called for urgent action to reduce prenatal alcohol exposure (PAE), but evidence on what is effective is scarce. We aimed to identify, evaluate, and synthesise evidence on content, process aspects, and effectiveness of UK PAE prevention initiatives.MethodsWe conducted a systematic search of published and grey literature on UK PAE prevention (PROSPERO: CRD42020209460); consultations with 61 academic, practice, policy, third sector, and public stakeholders; and semi-structured 12 interviews with pregnant people (who were aged ≥18 years and ≥12 weeks' gestation) and service providers to discuss experiences of PAE prevention. Participants were purposively sampled to cover each UK region and identified through maternity sites, social media and, for stakeholder consultees, researcher networks. Information from relevant PAE prevention initiatives from the literature was independently extracted by two reviewers. Ethical approval and informed consent were obtained for interviews, which were recorded and transcribed. Qualitative evidence was synthesised using thematic analysis. Quantitative data will be summarised using descriptive statistics and meta-analysis.FindingsWe identified 14 PAE prevention initiatives through literature searches (22 of 4064 results were eligible), stakeholder consultation, and interviews. Initiatives included screening and intervention, campaigns, and education or training. Seven initiatives were identified in the north of England. Two initiatives were identified in Scotland and two in Wales. The East of England, West Midlands, and South East of England had one each. None were identified in Southwest of England or Northern Ireland. Barriers to prevention included absence of resources, excessive workload, concerns around blame, and COVID-19. Enablers included workforce training and trust between pregnant people and service providers. Effectiveness of evidence was scarce.InterpretationKey strengths include extensive searches and multidisciplinary consultation. Data collection and analyses are ongoing and will be finalised before November, 2022. This research will provide a comprehensive analysis of current provision, providing crucial evidence to inform research and practice.FundingThe National Institute for Health and Care Research.ContributorsCM conceived of the study. CM wrote the study protocol with input from LZ, TD, AP, FdV, SB, HC, PC, RL, AM, RM, and DTR. CM designed interview schedules with input from LZ, SB, PC, RL, AM, RM, FdV, and the study public involvement panel. CM and FF conducted participant interviews. CM, LZ, SB, HC, PC, LH, AM, RM, DTR, and OS contributed to the identification of contacts and initiatives. CM, TD, and EG carried out literature searches and data extraction. CM and TD conducted analyses. CM wrote the abstract. All authors have seen and approved the final version of the abstract for publication.Declaration of interestsSB is chief executive of The National Organisation for Fetal Alcohol Spectrum Disorders. She is sometimes paid for providing presentations. This money goes back into the organisation. The National Organisation for Fetal Alcohol Spectrum Disorders accepts funding from the alcohol industry, government, private foundations, and trusts and individuals, but has a strict policy that funders have no influence on substance. PC was an expert contributor to the Department of Health and Social Care's report, ‘Fetal Alcohol Spectrum Disorder: Health Needs Assessment’. She has received funding from the Greater Manchester Health and Social Care Partnership to estimate the prevalence of Fetal Alcohol Spectrum Disorders in Greater Manchester, and from the Medical Research Council to develop an intervention for families affected by Fetal Alcohol Spectrum Disorders. She is an unpaid member of the Steering Board to oversee Greater Manchester's Preventing Alcohol Exposed Pregnancy Programme. RM is an unpaid advisor to various FASD charities and runs the National Clinic for Fetal Alcohol Spectrum Disorders.AcknowledgmentsThe study was funded by The National Institute for Health and Care Research School for Public Health Research Postdoctoral Launching Fellowship/ResNet ECR funding (McQuire). We would like to thank the members of our Public Participation and Involvement panel, who assisted with the design of the interview materials, study information sheets, and consent forms.

The aim of this study is to examine whether alcohol, tobacco and caffeine use in pregnancy might be causally associated with ADHD in offspring and use negative control and Mendelian Randomization methods to disentangle potential causal intrauterine effects.

BackgroundPoint estimation in Mendelian randomization (MR), an instrumental variable model, usually requires strong homogeneity assumptions beyond the core instrumental conditions. Bounding, which does not require homogeneity assumptions, is infrequently applied in MR.ObjectiveWe aimed to demonstrate computing nonparametric bounds for the causal risk difference derived from multiple proposed instruments in an MR study where effect heterogeneity is expected,MethodsUsing data from the Norwegian Mother, Father, and Child Cohort Study and Avon Longitudinal Study of Parents and Children (n=4457, 6216) to study the average causal effect of maternal pregnancy alcohol use on offspring attention deficit hyperactivity disorder symptoms, we proposed 11 maternal SNPs as instruments. We computed bounds assuming subsets of SNPs were jointly valid instruments, for all combinations of SNPs where the MR model was not falsified.ResultsThe MR assumptions were violated for all sets with more than 4 SNPs in one cohort and for all sets with more than 2 SNPs in the other. Bounds assuming one SNP was an individually valid instrument barely improved on assumption-free bounds. Bounds tightened as more SNPs were assumed to be jointly valid instruments, and occasionally identified directions of effect, though bounds from different sets varied.ConclusionsOur results suggest that, when proposing multiple instruments, bounds can contextualize plausible magnitudes and directions of effects. Computing bounds over multiple assumption sets underscores the importance of evaluating the assumptions of MR models.SynopsisStudy questionDo nonparametric bounds provide useful information in the context of MR studies of prenatal exposures with multiple proposed genetic instruments?What’s already knownPoint estimation in MR typically requires strong, unverifiable homogeneity assumptions beyond the core MR assumptions. Bounds, which do not require homogeneity assumptions, are rarely applied in MR.What this study addsWe computed bounds on the average causal effect of alcohol consumption during pregnancy on offspring ADHD symptoms in two European cohorts, proposing 11 genetic variants as instruments. Our results suggest that, when proposing multiple instruments, bounds can contextualize plausible magnitudes and directions of effects.

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

Genome-wide association meta-analysis (GWAMA) is an effective approach to enlarge sample sizes and empower the discovery of novel associations between genotype and phenotype. Independent replication has been used as a gold-standard for validating genetic associations. However, as current GWAMA often seeks to aggregate all available datasets, it becomes impossible to find a large enough independent dataset to replicate new discoveries. Here we introduce a method, MAMBA (Meta-Analysis Model-based Assessment of replicability), for assessing the “posterior-probability-of-replicability” for identified associations by leveraging the strength and consistency of association signals between contributing studies. We demonstrate using simulations that MAMBA is more powerful and robust than existing methods, and produces more accurate genetic effects estimates. We apply MAMBA to a large-scale meta-analysis of addiction phenotypes with 1.2 million individuals. In addition to accurately identifying replicable common variant associations, MAMBA also pinpoints novel replicable rare variant associations from imputation-based GWAMA and hence greatly expands the set of analyzable variants., In genome-wide association meta-analysis, it is often difficult to find an independent dataset of sufficient size to replicate associations. Here, the authors have developed MAMBA to calculate the probability of replicability based on consistency between datasets within the meta-analysis.

Norwegian health survey data (1987 – 2003) were analysed to determine if binge drinking increases the risk of incident major events from ischemic heart disease (IHD) and stroke. Among current drinkers reporting average alcohol intakes between 2 to 60 g/day (n = 44,476), frequent binge drinking (5+ units ≥ once per month) was not associated with a greater risk of IHD (adjusted hazard ratio = 0.91, 95% confidence interval: 0.76, 1.09) nor stroke (adjusted hazard ratio = 0.98, 95% confidence interval: 0.81, 1.19), in comparison with participants who reported that they never or only infrequently (

Additional file 7. Estimates of the effects of DNAm-Alc in ARIES offspring at birth and in mothers during pregnancy on offspring AUDIT at adolescence considered both in separate single-predictor models and simultaneously.

Additional file 2. R2 between DNAm-Alcs and alcohol intake (log(g/day +1)) in ARIES parents at midlife and offspring at adolescence, excluding self-reported non-drinkers.

Additional file 6. Area under the curve for prediction of binary alcohol categories by DNAm-Alcs in HN5000.

Additional file 5. Area under the curve for prediction of ‘at risk’ category of drinkers by DNAm-Alcs.

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression., What's new? Alcohol may spur prostate cancer progression, though it does not appear to affect incidence, according to new analysis. Variation in genes involved in alcohol metabolism affect how much the body is exposed to carcinogenic metabolites. These authors examined 68 genetic variants in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes, seeking a link with prostate cancer risk. While they found no evidence that these variants alter prostate cancer incidence, they did show that SNPs in the ALDH1A2 gene affect prostate cancer mortality. From a public health standpoint, these results suggest reducing alcohol consumption could slow prostate cancer disease progression.

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.

BACKGROUND: Heavy alcohol use during pregnancy can cause considerable developmental problems for children, but effects of light-moderate drinking are uncertain. This study examined possible effects of moderate drinking in pregnancy on children's conduct problems using a Mendelian randomisation design to improve causal inference. METHODS: A prospective cohort study (ALSPAC) followed children from their mother's pregnancy to age 13 years. Analyses were based on 3,544 children whose mothers self-reported either not drinking alcohol during pregnancy or drinking up to six units per week without binge drinking. Children's conduct problem trajectories were classified as low risk, childhood-limited, adolescence-onset or early-onset-persistent, using six repeated measures of the Strengths and Difficulties Questionnaire between ages 4-13 years. Variants of alcohol-metabolising genes in children were used to create an instrumental variable for Mendelian randomisation analysis. RESULTS: Children's genotype scores were associated with early-onset-persistent conduct problems (OR = 1.29, 95% CI = 1.04-1.60, p = .020) if mothers drank moderately in pregnancy, but not if mothers abstained from drinking (OR = 0.94, CI = 0.72-1.25, p = .688). Children's genotype scores did not predict childhood-limited or adolescence-onset conduct problems. CONCLUSIONS: This quasi-experimental study suggests that moderate alcohol drinking in pregnancy contributes to increased risk for children's early-onset-persistent conduct problems, but not childhood-limited or adolescence-onset conduct problems.

BACKGROUND: Mendelian randomization studies have so far restricted attention to linear associations relating the genetic instrument to the exposure, and the exposure to the outcome. In some cases, however, observational data suggest a non-linear association between exposure and outcome. For example, alcohol consumption is consistently reported as having a U-shaped association with cardiovascular events. In principle, Mendelian randomization could address concerns that the apparent protective effect of light-to-moderate drinking might reflect 'sick-quitters' and confounding. METHODS: The Alcohol-ADH1B Consortium was established to study the causal effects of alcohol consumption on cardiovascular events and biomarkers, using the single nucleotide polymorphism rs1229984 in ADH1B as a genetic instrument. To assess non-linear causal effects in this study, we propose a novel method based on estimating local average treatment effects for discrete levels of the exposure range, then testing for a linear trend in those effects. Our method requires an assumption that the instrument has the same effect on exposure in all individuals. We conduct simulations examining the robustness of the method to violations of this assumption, and apply the method to the Alcohol-ADH1B Consortium data. RESULTS: Our method gave a conservative test for non-linearity under realistic violations of the key assumption. We found evidence for a non-linear causal effect of alcohol intake on several cardiovascular traits. CONCLUSIONS: We believe our method is useful for inferring departure from linearity when only a binary instrument is available. We estimated non-linear causal effects of alcohol intake which could not have been estimated through standard instrumental variable approaches.

ObjectiveTo use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.DesignMendelian randomisation meta-analysis of 56 epidemiological studies.Participants261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.Main outcome measuresOdds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.ResultsCarriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).ConclusionsIndividuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies.PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for [...].

This is an update of incidence and mortality cancer data provided by the Italian Network of Cancer Registry (AIRTUM) relative to the period 2003-2005.AIRTUM is a network of general and specialized population-based cancer registries that covers about 1/3 of the Italian resident population (www.registri-tumori.it). Incidence and mortality data for the period 2003-2005 are based on 20 Registries. The five most frequently diagnosed cancers were: - prostate (18.5%), non melanoma skin (15.8%), lung (13.1%), colorectal (12.0%), bladder (5.7%) among males; - breast (24.9%), non melanoma skin (15.1%), colorectal (11.9%), lung (5.0%) and stomach (4.1%) among females. In the same period the most frequent causes of cancer death were: - cancer of the lung (27.6%), colorectal (10.7%), prostate (8.5%), stomach (7.3%) and liver (6.1%) among males; - breast cancer (16.3%), colorectal (11.9%), lung (10.3%), stomach (7.2%) and pancreas (6.5%) among females. According to the age-specific incidence rates one man and one woman every two will receive a cancer diagnosis during his/hers life (from birth to the age of 84 years). From 1993-1995 to 2003-2005, overall crude cancer incidence rate (males and females together) increased from 555.4 to 654.8 x 100,000. Standardization showed that 63% of this increase was due to ageing of the population. Moreover, most of the residual increase was among those cancer sites (breast, prostate, colorectal, thyroid and melanoma) for which early detection may have played a relevant role in anticipating (and therefore increasing) the number of diagnoses. Due to population ageing also overall cancer mortality did not show any decrease when crude rates were compared. On the contrary, standardized mortality rates (all cancers together) showed a strong decrease (311.4 vs. 266.5 x 100.000). The risk of receiving a diagnosis or dying because of cancer is still lower in residents in the regions of the South of Italy than in those of Central and Northern Italy, but they are becoming more and more similar. In Italy cancer incidence and mortality rates are similar to those in northern European countries and in USA among males, but they are still lower for women.

Additional file 1. R2 between DNAm-Alcs and measures of alcohol intake (log(g/day +1)) and AUDIT score, in ARIES parents at midlife and offspring at adolescence with adjustment of DNAm-Alcs for concurrent smoking.

Additional file 3. R2 between DNAm-Alcs and alcohol intake (log(g/day +1)) and AUDIT score in HN5000.

Additional file 3. R2 between DNAm-Alcs and alcohol intake (log(g/day +1)) and AUDIT score in HN5000.

Additional file 1. R2 between DNAm-Alcs and measures of alcohol intake (log(g/day +1)) and AUDIT score, in ARIES parents at midlife and offspring at adolescence with adjustment of DNAm-Alcs for concurrent smoking.

OBJECTIVES: the aim of the present monograph is to update the estimation of the number of people living with cancer in Italy, to describe geographic variability, and estimate the number of long-term survivors, i.e., people living five years or more after a cancer diagnosis. MATERIALS AND METHODS: the study included the data of the AIRTUMdatabase. Twenty-four Cancer Registries (CRs) (covering 27% of the Italian population) collected information on the incidence and vital status of 1,275,353 cases diagnosed between 1978 and 2005. For each CR, the observed prevalence was calculated up to the maximum observable duration. To estimate the complete prevalence (all living patients, independently from time since diagnosis) and the prevalence for lengths of time exceeding the CR maximum duration of registration, the observed prevalence was corrected through a completeness index. Completeness indices, gender, age and site specific, were estimated by means of statistical regression models using cancer incidence and survival data available from CRs with more than 15 years of observation. As of 1 January 2006, the prevalence was estimated (as absolute numbers and as a proportion per 100,000 inhabitants) for 46 cancer sites, by gender, age class, years since diagnosis and geographic areas. RESULTS: as of 2006, 2,244,000 persons (4%of the Italian population) were alive with a cancer diagnosis. A relevant geographic variability emerged, with proportions between 4%-5% among CRs in the Centre and North of Italy, and proportions between 2%-3% in the South. Forty-four percent of prevalent subjects (988,000) were males and 56% (1,256,000) females. Fifty-seven percent (1,285,680 people, 2.2% of total population) of these patients was represented by long-term survivors. In patients aged 75 years or more, the proportions of prevalent cases were 19%in males and 13%in females, and 10%between 60 and 75 years of age in both genders.More than half a million Italian women were alive with a breast cancer diagnosis (42%of women with a neoplasm), followed by women with cancers of the colonrectum (12%), corpus uteri (7%), thyroid (5%), and cervix uteri (4%). In men, 22%of prevalent cases (216,716) included patients with prostate cancer, 18% with bladder cancer, and 15%with colon-rectum cancer. Percentages of long-term survivors higher than 70% were reported for cancers of the cervix uteri (82% at five years, and 55% at 15 years from diagnosis), Hodgkin lymphoma, testis, brain and central nervous system, bone and connective tissue. Many patients with these types of cancers (often occurring in young people) can be considered "cured", i.e., with a life expectancy overlapping that of the general population.The estimated proportions of prevalent cases emerging from this study in Italy were quite similar to those reported in Northern Europe, but at least 15%lower than those in the United States. CONCLUSIONS: in 2006, the number of prevalent cases nearly doubled compared to 1992. The increase over time in the proportion of elderly patients, related to population ageing, requires adequate health policies. Knowing the number of people alive many years after cancer diagnosis (either cured or long-term survivors) provides the scientific bases for the definition of health policies focusing on them. Furthermore, it promotes the conduction of studies aimed at improving the present knowledge on the quality of life of these patients during and after the active phase of treatments, in addition to studies on the long-term effects of treatments.

Refereed/Peer-reviewed