Biomarkers for personalised prevention of chronic diseases: a common protocol for three rapid scoping reviews.

INTRODUCTION: Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the "Personalised Prevention Roadmap for the future HEalThcare" (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. OBJECTIVE: To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. METHODS: Three rapid scoping reviews are being conducted in parallel (February-June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. INCLUSION CRITERIA: Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. SYSTEMATIC REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).

Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain).

There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008-2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged <65, with a low O-SES, D-SES and stable low SM are less likely to have healthy behaviours in the case of both women (physically active: OR = 0.65 CI = 0.45-0.94, OR = 0.71 CI = 0.52-0.98, OR = 0.61 CI = 0.41-0.91) and men (non-smokers: OR = 0.44 CI = 0.26-0.76, OR = 0.54 CI = 0.35-0.83, OR = 0.41 CI 0.24-0.72; physically active: OR = 0.57 CI = 0.35-0.92, OR = 0.64 CI = 0.44-0.95, OR = 0.53 CI = 0.23-0.87). However, for those aged ≥65, this probability is higher in women with a low O-SES and D-SES (non-smoker: OR = 8.09 CI = 4.18-15.67, OR = 4.14 CI = 2.28-7.52; moderate alcohol consumption: OR = 3.00 CI = 1.45-6.24, OR = 2.83 CI = 1.49-5.37) and in men with a stable low SM (physically active: OR = 1.52 CI = 1.02-1.26). In the case of men, the same behaviour pattern is observed in those with a low O-SES as those with upward mobility, with a higher probability of co-occurring behaviours (three-to-four behaviours: OR = 2.00 CI = 1.22-3.29; OR = 3.13 CI = 1.31-7.48). The relationship of O-SES, D-SES and SM with healthy behaviours is complex and differs according to age and gender.

Mediterranean dietary pattern is associated with lower incidence of premenopausal breast cancer in the Seguimiento Universidad de Navarra (SUN) Project.

OBJECTIVE: Due to the growing interest in the role of dietary patterns (DPs) on chronic diseases, we assessed the association between a posteriori identified DPs in the Seguimiento Universidad de Navarra (SUN) Project - a prospective cohort study in a Mediterranean country - and breast cancer (BC) risk. DESIGN: DPs were ascertained through a principal component analysis based on 31 predefined food groups. BC cases were initially identified through self-report or, if deceased, from death certificates or by notification by the next kin. Women reporting BC were asked to provide a copy of their medical report and diagnoses for confirmation purposes. We fitted Cox regression models to assess the association between adherence to the identified DPs and BC risk. SETTING: Spanish university graduates. PARTICIPANTS: We included 10 713 young and middle-aged - mainly premenopausal - women. RESULTS: After a median follow-up of 10·3 years, we identified 100 confirmed and 168 probable incident BC cases. We described two major DPs: 'Western dietary pattern' (WDP) and 'Mediterranean dietary pattern' (MDP). A higher adherence to a WDP was associated with an increased risk of overall BC (multivariable-adjusted HR for confirmed BC Q4 v. Q1 1·70; 95 % CI 0·93, 3·12; P for trend = 0·045). Contrarily, adherence to a MDP was inversely associated with premenopausal BC (multivariable-adjusted HR Q4 v. Q1 0·33; 95 % CI 0·12, 0·91). No significant associations were observed for postmenopausal BC. CONCLUSIONS: Whereas a higher adherence to the WDP may increase the risk of BC, a higher adherence to the MDP may decrease the risk of premenopausal BC.

Trends in mortality from cutaneous malignant melanoma in Spain (1982-2016): sex-specific age-cohort-period effects.

BACKGROUND: Mortality from malignant cutaneous melanoma increased alarmingly during the second half of the 20th century in Spain and other European countries. OBJECTIVE: The aim was to analyse sex- and age-specific trends in melanoma mortality in Spain in the period 1982-2016. METHODS: European age-standardized melanoma mortality rates during the period 1982-2016 were calculated from mortality figures provided by the National Statistics Institute. Joinpoint regressions were used to identify significant points of change in trends and to compute average annual per cent change (AAPC). Age-cohort-period models were fitted to explore the effect of these variables on mortality. RESULTS: During the period 1982-2016, age-standardized melanoma mortality rates increased in Spain from 0.90 to 1.80 deaths per 100 000 people in men and from 0.64 to 1.11 per 100 000 in women, rising noticeably from 1982 to 1995 in both sexes and in all age groups. From the mid-90s different trends were observed depending on sex and age: there was a decrease in mortality in the population younger than 45 years (AAPC -2 in both sexes) and aged 45-64 years (AAPC -1 among men and -0.2 among women), but in the group over 64 years rates continued to increase (AAPC 1.7 and 0.2, respectively, for men and women). The mortality sex ratio decreased in the younger population but increased in older individuals. A cohort effect was observed with lower mortality in the cohorts born after 1943 in men and 1956 in women. There was also a period effect with decreased mortality rates at the beginning of the 1990s. CONCLUSIONS: Melanoma mortality rates in Spain increased during the last decades of the 20th century; however, later they stabilized in women and began to decrease in younger cohorts and middle-aged men. Promotion of primary and secondary prevention measures should continue, with particular emphasis on males over 65 years.

Levels and predictors of persistent organic pollutants in an adult population from four Spanish regions.

This research aimed to assess serum concentrations of a group of persistent organic pollutants (POPs) in a sample of adults recruited in four different regions from Spain and to assess socio-demographic, dietary, and lifestyle predictors of the exposure. The study population comprised 312 healthy adults selected from among controls recruited in the MCC-Spain multicase-control study. Study variables were collected using standardized questionnaires, and pollutants were analyzed by means of gas chromatography with electron capture detection. Multivariable analyses were performed to identify predictors of log-transformed pollutant concentrations, using combined backward and forward stepwise multiple linear regression models. Detection rates ranged from 89.1% (hexachlorobenzene, HCB) to 93.6% (Polychlorinated biphenyl-153 [PCB-153]); p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) showed the highest median concentrations (1.04ng/ml), while HCB showed the lowest (0.24ng/ml). In the multivariable models, age was positively associated with HCB, p,p'-DDE, and PCB-180. BMI was associated positively with p,p'-DDE but negatively with PCB-138. Total accumulated time residing in an urban area was positively associated with PCB-153 concentrations. The women showed higher HCB and lower p,p'-DDE concentrations versus the men. Notably, POP exposure in our study population was inversely associated with the breastfeeding received by participants and with the number of pregnancies of their mothers but was not related to the participants' history of breastfeeding their children or parity. Smoking was negatively associated with HCB and PCB-153 concentrations. Consumption of fatty foods, including blue fish, was in general positively associated with POP levels. Although POP environmental levels are declining worldwide, there is a need for the continuous monitoring of human exposure in the general population. The results of the present study confirm previous findings and point to novel predictors of long-term exposure to persistent organic pollutants.

Spanish Mediterranean diet and other dietary patterns and breast cancer risk: case-control EpiGEICAM study.

BACKGROUND: Although there are solid findings regarding the detrimental effect of alcohol consumption, the existing evidence on the effect of other dietary factors on breast cancer (BC) risk is inconclusive. This study aimed to evaluate the association between dietary patterns and risk of BC in Spanish women, stratifying by menopausal status and tumour subtype, and to compare the results with those of Alternate Healthy Index (AHEI) and Alternate Mediterranean Diet Score (aMED). METHODS: We recruited 1017 incident BC cases and 1017 matched healthy controls of similar age (±5 years) without a history of BC. The association between 'a priori' and 'a posteriori' developed dietary patterns and BC in general and according to menopausal status and intrinsic tumour subtypes (ER+/PR+ and HER2-; HER2+; and ER-/PR- and HER2-) was evaluated using logistic and multinomial regression models. RESULTS: Adherence to the Western dietary pattern was related to higher risk of BC (OR for the top vs the bottom quartile 1.46 (95% CI 1.06-2.01)), especially in premenopausal women (OR=1.75; 95% CI 1.14-2.67). In contrast, the Mediterranean pattern was related to a lower risk (OR for the top quartile vs the bottom quartile 0.56 (95% CI 0.40-0.79)). Although the deleterious effect of the Western pattern was similarly observed in all tumour subtypes, the protective effect of our Mediterranean pattern was stronger for triple-negative tumours (OR=0.32; 95% CI 0.15-0.66 and Pheterogeneity=0.04). No association was found between adherence to the Prudent pattern and BC risk. The associations between 'a priori' indices and BC risk were less marked (OR for the top vs the bottom quartile of AHEI=0.69; 95% CI 0.51-0.94 and aMED=0.74; 95% CI 0.46-1.18)). CONCLUSIONS: Our results confirm the harmful effect of a Western diet on BC risk, and add new evidence on the benefits of a diet rich in fruits, vegetables, legumes, oily fish and vegetable oils for preventing all BC subtypes, and particularly triple-negative tumours.

[Compliance with current dietary recommendations and geographical variability of diet in women participating in 7 screening programs for breast cancer in Spain]. / Cumplimiento de las recomendaciones dietéticas vigentes y variabilidad geográfica de la dieta en mujeres participantes en 7 programas de cribado de cáncer de mama en España.

INTRODUCTION: A healthy diet is especially important during menopause, a period which increases the risk of various health problems. We analyzed the diet of periand postmenopausal Spanish women and the degree of compliance with current recommendations. MATERIAL AND METHODS: We studied 3574 women 45-68 years old who attended breast cancer screening programmes in 7 centres (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was collected using a food frequency questionnaire validated for the Spanish population. For the assessment of compliance with current guidelines we used the recommendations by the Spanish Society of Community Nutrition for food groups intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy, vitamins and minerals intake. RESULTS: The 29% of women were obese and 42% overweight. The average caloric intake was 2.053 kcal (SD 480). The general energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and 20% from proteins. There was a low vitamin D intake in all centres of the study, with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A Coruña and Burgos was also detected. Intake of dairy products and vegetables was high in all the study centers. The consumption of fruits and vegetables was very heterogeneous, with high intakes observed in Mallorca and Valencia and low for both food groups in A Coruña. The olive oil intake was high in all centers except Burgos with 74.3% of the women studied below the recommended 3 servings per day. CONCLUSIONS: A diet with less fat and protein and a higher consumption of vegetables, nuts and foods rich in carbohydrate might balance the energy intake and improve the quality of the diet correcting the low intakes of vitamins D and E. These recommendations are especially important in cities far from the Mediterranean coast where more breaches have been detected over the current recommendations with a lower adherence to the Mediterranean diet.

Cancer mortality trends in Spain: 1980-2007.

INTRODUCTION: Since the 1990s, there has been a downturn in mortality for specific types of tumour in Spain and other European countries. This article reports on the current situation of cancer mortality in Spain, as well as mortality trends over the period 1980-2007, and provides an overview of cancer mortality trends in Europe in recent years. METHODS: Data were sourced from the National Statistics Institute (Instituto Nacional de Estadística - INE) and the World Health Organization mortality database. Mortality trends were studied using change-point Poisson regression models. RESULTS: All-cancer mortality decreased in both sexes from 1980 to 2007, owing to the fact that the tumours responsible for the highest number of deaths registered declining trends from the mid-1990s onwards. In men, mortality due to stomach and prostate cancer fell by >3% per annum in the last 10 years of the study period. In women, the largest contributions to the fall in cancer mortality were due to breast and colorectal cancers. In contrast, female mortality due to smoking-related cancers rose significantly. Within the European context, Spain's estimated 2005 mortality rates were intermediate for men and low for women. CONCLUSION: Cancer control is progressing in the right direction in Spain. Further interventions directed to reduce tobacco-related cancer mortality remain a priority, particularly for women.

The moderate decrease in invasive cervical cancer incidence rates in Spain (1980-2004): limited success of opportunistic screening?

BACKGROUND: Despite its low incidence, invasive cervical cancer (ICC) is still a public health concern in Spain, due to its being perceived as an avoidable neoplasm. Social changes in recent decades may have increased the risk of ICC among Spanish females. This study sought to update incidence trends in Spanish registries. PATIENTS AND METHODS: We studied the ICC incidence time trend over the period 1980-2004 using data from 13 Spanish population-based cancer registries, analysing all cases and the two main histological types, i.e. squamous cell carcinoma (SCC) and adenocarcinoma (AC). Change-point Poisson regression models were fitted for all women and for the following three age groups: 25-44, 45-64 and > or =65 years. Age-period-cohort models were used to study cohort and period effect. RESULTS: ICC incidence showed a moderate decrease (annual percentage change: -0.9%; 95% CI -1.3% to -0.5%). Whereas rates among younger women rose sharply by 5.5% until 1990, when they began to descend by 1.2% annually, among women aged > or =45 years they declined by 1.5% per annum. In the last decade of the study period, divergent trends were found for SCC and AC, i.e. downward versus upward, respectively. Risk increased with birth cohort after 1940-45 but the period effect showed opposite trends for the two histological types. CONCLUSION: Cervical cancer incidence rates have decreased moderately in Spain, a trend consistent with the preventive effect of widespread opportunistic screening.

WT 1 expression in nevi and melanomas: a marker of melanocytic invasion into the dermis.

BACKGROUND: WT1, first recognized as a tumor suppressor gene involved in the development of Wilms' tumor, may have apparently contradictory findings and functions. As WT1 has been identified as a molecular target for cancer immunotherapy, immunodetection of WT1 in tumor cells has become an essential step in cancer studies. METHODS: We compare the expression of this protein among different types of melanocytic nevi and among stages in primary melanoma progression. Tissue microarrays containing normal tissues and 271 primary melanocytic lesion samples (163 primary melanomas and 108 nevi) were studied by immunohistochemistry using monoclonal antibody against WT1. RESULTS AND DISCUSSION: The present study shows these: 1. WT1 protein is predominantly expressed in the cytoplasm of the neoplastic cells. 2. A higher rate of WT1 staining in melanocytic nevi against melanomas has been observed. 3. WT1 expression is increased in advanced stages of melanoma progression: a significant (p < 0.05) increase of expression of WT1 was detected in vertical cases 46.5% vs. radial cases 16.0%, in high levels of Clark (IV, V) 57.4% vs. low levels (I, II, III) 33.0% and when comparing depth of invasion within thickness subgroups. 4. Finally, this study establishes an association of WT1 protein expression with shorter overall survival in melanoma.

Do sex and site matter? Different age distribution in melanoma of the trunk among Swedish men and women.

BACKGROUND: Recent research on cutaneous malignant melanoma (CMM) points to the coexistence of several biological pathways linked to the anatomical site of the lesion, which could lead to this neoplasm. Although the different anatomical distribution of CMM by sex is usually attributed to gender-specific patterns of sun exposure, it has been suggested that an alternative explanation might lie in gender-specific site susceptibility. OBJECTIVES: This paper aimed at analysing the age distribution of CMM by site and sex to gain in-depth knowledge of differences between the sexes. METHODS: Using a large Swedish cohort comprising 2 992 166 workers, Poisson models were fitted to estimate age-specific incidence rates by site and sex, duly adjusted for several factors that might account for changes in environmental exposures (period, birth cohort, socioeconomic level, latitude and rurality). RESULTS: Incidence rates were 17.4 cases per 100 000 person-years in men and 16.5 in women. Sex differences were particularly striking for CMM of the trunk, where both crude and adjusted incidence rates displayed a steady increase with age in men, but reached a plateau in women at around four cases per 100 000 person-years from the 40-45-year age group (perimenopausal period) upwards. There was an almost fivefold increase in the sex ratio for this body site between the younger and older age groups, a difference which could not be attributed to period or cohort effects. CONCLUSIONS: If different aetiological pathways can be assumed to lead to melanoma, then disparities between men and women, particularly in CMM of the trunk, suggest that a possible interaction between site and sex should be borne in mind.

Acute health problems among subjects involved in the cleanup operation following the Prestige oil spill in Asturias and Cantabria (Spain).

The purpose of this study was to evaluate exposure conditions and acute health effects in subjects participating in the Prestige oil spill cleanup activities and the association between these and the nature of the work and use of protection devices in the regions of Asturias and Cantabria (Spain). The sample comprised 400 subjects in each region, selected from a random sampling of all persons involved in cleanup activities, stratified by type of worker and number of working days. Data were obtained via a structured questionnaire and included information on specific tasks, number of working days, use of protective materials, and acute health effects. These effects were classified into two broad groups: injuries and toxic effects. Data analysis was performed using complex survey methods. Significant differences between groups were evaluated using Pearson's chi(2) test. Unconditional logistic regression was used to compute odds ratios and 95% confidence intervals. Bird cleaners accounted for the highest prevalence of injuries (19% presented with lesions). Working more than 20 days in highly polluted areas was associated with increased risk of injury in all workers. Occurrence of toxic effects was higher among seamen, possibly due to higher exposure to fuel oil and its components. Toxic effects were more frequent among those working longer than 20 days in highly polluted areas, performing three or more different cleaning activities, having skin contact with fuel oil on head/neck or upper limbs, and eating while in contact with fuel or perceiving disturbing odors. No severe disorders were identified among individuals who performed these tasks. However, potential health impact should be considered when organizing cleanup activities in similar environmental disasters.

Municipal pleural cancer mortality in Spain.

BACKGROUND: Pleural cancer is a recognised indicator of exposure to asbestos and mesothelioma mortality. AIMS: To investigate the distribution of municipal mortality due to this tumour, using the autoregressive spatial model proposed by Besag, York, and Mollie. METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardised mortality ratios, smoothed relative risk (RR) estimates, and the distribution of the posterior probability that RR >1. RESULTS: There was a higher risk of death due to pleural cancer in well defined towns and areas, many of which correspond to municipalities where asbestos using industries once existed for many years, the prime example being the municipal pattern registered for Barcelona Province. The quality of mortality data, the suitability of the model used, and the usefulness of municipal atlases for environmental surveillance are discussed.

[State of cancer in Spain: incidence]. / Situación del cáncer en España: incidencia.

It is estimated that at present in Spain around 162,000 cases of cancer are diagnosed each year (without including non-melanoma skin cancer), of which 25,600 correspond to colorectal carcinomas, which is the most frequent of all tumours in absolute terms. The next tumour in terms of frequency is lung cancer with 18,800 new cases, followed by breast cancer in women with 15,979 cases. When the incidence of cancer is compared with that in neighbouring countries, Spain shows adjusted rates in men higher than those of the average for the EU, occupying the 5th place. However, in women, Spain shows the lowest rates together with Greece. Spain occupies the first place for cancer of the bladder in men, with rates that are considerably higher than those of the rest of the countries. It is important to verify the increase underway in the incidence of cancer in Spain and the contrast that this represents facing the evolution of mortality. For many important tumoral localisations (lung, stomach, bladder), the population registers do not cover the provinces where there is a greater mortality.

Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men.

AIMS: To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers. METHODS: Male workers employed in 1970 and living in the country in 1960 were followed up from 1971 to 1989 using the Swedish Registers of Death and Cancer. A more specifically exposed subcohort included men reporting the same occupation in 1960 and 1970. For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. To diminish the influence of socioeconomic factors, intrasector analyses, comparing only jobs belonging to the same occupational sector, were performed. Risk patterns for different locations were compared. RESULTS: High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those found in thorax, the most frequent location. Correlation between head/neck and thorax was moderate. Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and for aircraft pilots/navigators/flight engineers in lower limbs. CONCLUSIONS: High RRs in the trunk among occupations with UV exposure from artificial sources suggest an effect not restricted to exposed sites. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers suggests local effects of exposures. The not previously reported risk excess in this job and in fur related processes, and the RR in electrical fitters and telephone/telegraph installers deserve further investigation. Disparities between locations, as RRs in thorax and limbs, may reflect differences in aetiological mechanisms.