A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. METHODS: We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. RESULTS: We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support. CONCLUSIONS: This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.

Understanding consumers' perceptions towards Iberian pig production and animal welfare.

The Spanish market offers a greater variety of Iberian pork products. The aim of this paper is to determine the perception of consumers of several aspects of Iberian pig production and animal welfare depending on the consumers' characteristics. Consumers from two Spanish regions (n = 403) answered a questionnaire about their beliefs and the importance of pig production, their purchase intentions and their willingness to pay. Consumers were segmented according to their level of knowledge about Iberian pig production. The results of this work indicate that consumers have poor knowledge about Iberian pig production. Even so, consumers show a remarkable preference for Iberian products, especially when the animals are reared freely and in natural conditions, giving great importance to animal welfare. Consumer preferences indicate the importance of emphasizing Iberian traditional pig product characteristics on the label to promote their purchase choices.

Community Health Behaviors and Geographic Variation in Early-Onset Colorectal Cancer Survival Among Women.

INTRODUCTION: Despite overall reductions in colorectal cancer (CRC) morbidity and mortality, survival disparities by sex persist among young patients (age <50 years). Our study sought to quantify variance in early-onset CRC survival accounted for by individual/community-level characteristics among a population-based cohort of US women. METHODS: Geographic hot spots-counties with high early-onset CRC mortality rates among women-were derived using 3 geospatial autocorrelation approaches with Centers for Disease Control and Prevention national mortality data. We identified women (age: 15-49 years) diagnosed with CRC from 1999 to 2016 in the National Institutes of Health/National Cancer Institute's Surveillance, Epidemiology, and End Results program. Patterns of community health behaviors by hot spot classification were assessed by Spearman correlation (ρ). Generalized R values were used to evaluate variance in survival attributed to individual/community-level features. RESULTS: Approximately 1 in every 16 contiguous US counties identified as hot spots (191 of 3,108), and 52.9% of hot spot counties (n = 101) were located in the South. Among 28,790 women with early-onset CRC, 13.7% of cases (n = 3,954) resided in hot spot counties. Physical inactivity and fertility were community health behaviors that modestly correlated with hot spot residence among women with early-onset CRC (ρ = 0.21 and ρ = -0.23, respectively; P < 0.01). Together, individual/community-level features accounted for distinct variance patterns in early-onset CRC survival among women (hot spot counties: 33.8%; non-hot spot counties: 34.1%). DISCUSSION: Individual/community-level features accounted for approximately one-third of variation in early-onset CRC survival among women and differed between hot spot vs non-hot spot counties. Understanding the impact of community health behaviors-particularly in regions with high early-onset CRC mortality rates-is critical for tailoring strategies to reduce early-onset CRC disparities.

[New therapeutic strategies for multiple myeloma. Efficacy and cost-effectiveness analyses]. / Nuevas estrategias terapéuticas en el tratamiento del mieloma múltiple. Análisis de su eficacia y coste-efectividad.

The objective of the present article is the review of the most important therapeutic innovations in the treatment of multiple myeloma in terms of efficacy and cost-effectiveness. Besides autologous transplant with peripheral-blood stem-cell, thalidomide establishes as one of the most powerful therapeutic tools in induction and maintenance treatment and together with lenalidomide and bortezomib as therapy for relapsing/refractory multiple myeloma. Considering, the last named situation thalidomide can be an adequate therapeutical option in combination with dexamethasone. Under a strictly pharmacoeconomic point of view, lenalidomide and bortezomib seem to be additional alternatives in patients previously treated with thalidomide.

[Trends in social inequalities in mortality in the city of Seville [Spain] [1994-2002]]. / Evolución de las desigualdades sociales en la mortalidad general de la ciudad de Sevilla (1994-2002).

OBJECTIVES: To know trends of social inequalities in general mortality in Seville (Spain) between 1997 and 2002. MATERIAL AND METHOD: Socioeconomic level of its the residential census tracts was assigned for each death, taken from the Socio-economic Synthetic Index built up after applying a principal components analysis from 2001 census variables. Using mortality indicators its magnitude and trend was described according socio-economic level. RESULTS: General mortality standardized rates by age in the census tracts of lowest socio-economic level were 1.32 and 1.25 times greater than in the highest census tracts in men and 1.19 and 1.08 in women respectively in each periods. The truncated rates ratio and potential years of lost life in men went from 1.66 to 2.28 in men and 1.74 to 2.10 in women, respectively. The four years difference in life expectancy at birth between the census tracts of highest and lower level remained unchanged in men, and fell from 1.90 to 0.82 in women. The population attributable risk (all ages) went from 13.18% to 10.46% in men and 10.02% to 2.58% in women. CONCLUSIONS: Social inequalities in mortality for the general population decreased mainly in women. The inequalities increased in the early death and between 35-64 years old in men, basically due to a reduced mortality in higher socio-economic level census tracts.