Atypical fundoscopic manifestation with good visual prognosis in familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

PURPOSE: Pathogenic variants in the CLDN19 gene are responsible for Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) with ocular pathology (MIM *248190). Our objective was to delineate the ophthalmological and genetic manifestations of a patient with FHHNC and a pathogenic variant in CLDN19. CASE REPORT: A 25-year-old woman presented with renal involvement and a best-corrected visual acuity of 20/25 in the right eye and finger-counting ability in the left eye. The patient exhibited high myopia, convergent strabismus, and chorioretinal atrophic plaques in the perifoveal and peripapillary areas. We conducted a comprehensive ophthalmological examination, including refraction, fundoscopy, color and autofluorescence retinography, optical coherence tomography, and electrophysiology tests. Additionally, next-generation sequencing was performed using Illumina NextSeq500. We identified a homozygous missense variant, c.59G>A p.Gly20Asp, in the CLDN19 gene as the cause of renal and ocular manifestations. CONCLUSION: FHHNC is associated with various ocular alterations. The unique retinal disorders described in this article suggest a more favorable visual prognosis compared to those previously reported in the literature. Determining the phenotypic diversity of this disease may aid in the diagnosis and management of future cases.

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).

[Cost-effectiveness analysis of fracture liaison services in Catalonia]. / Análisis de coste-efectividad de las Unidades de Coordinación de Fracturas en Cataluña.

OBJECTIVE: To assess the cost-effectiveness of Fracture Liaison Service (FLS) compared to the standard of care for secondary prevention of fragility fractures form the perspective of the Catalan Health Service. METHODS: Cost-utility assessment through a Markov model that simulated disease progression of a patients' cohort candidates to initiate antiosteoporotic treatment after a fragility fracture. A time horizon of 10 years and a 6-month duration per cycle was established. Clinical, economics and quality of life parameters were obtained from the literature and derived from four Catalan FLS. The Catalan Health Service perspective was adopted, considering direct health costs expressed in 2022 euros. A 3% discount rate was applied on costs and outcomes. Uncertainty was assessed through multiple sensitivity analyses. RESULTS: Compared to the standard of care, FLS would promote antiosteoporotic initiation and persistence, reducing the incidence and mortality associated with subsequent fragility fractures. This incremental clinical benefit was estimated at 0.055 years and 0.112 quality-adjusted life years (QALYs) per patient. A higher cost (€1,073.79 per patient) was estimated, resulting into an incremental cost-utility ratio of €9,602.72 per QALYs gained. The sensitivity analyses performed were consistent, corroborating the robustness and conservative approach of the base-case. CONCLUSIONS: The introduction of FLS for the secondary prevention of FF would represent a cost-effective strategy from the Catalan Health Service perspective.

Reproductive Health Practices in Spanish Women Who Underwent Voluntary Termination of Pregnancy.

Background: The incidence of Voluntary Termination of Pregnancy (VTP) is an important indicator of unplanned pregnancies and the differences in the functioning of contraceptive services and the effectiveness of their use. Its analysis is essential for monitoring the well-being of women and their partners. Our aim was to analyse the socio-demographic profile of women who request voluntary termination of pregnancy in the province of Salamanca, as well as their satisfaction with the intervention and its influence on their contraceptive methods. Methods: An intervention study (before-after) designed without a control group, including all women requesting a voluntary termination of pregnancy through the Salamanca Public Health System. Socio-demographic and reproductive health variables were used. After the termination of pregnancy, a satisfaction survey and analysis of consequences were carried out. Results: A total of 176 surveys were obtained. Women who underwent VTP in Salamanca were between 20 and 25 years old, had secondary education but were still studying or working, lived alone and had no children. The most commonly used contraceptive method was the condom (55%), followed by the pill (25%). The most frequent reason for termination of pregnancy was economic (47.7%). The abortion entailed a significant change in contraception. Whereas before the abortion only 34% used a hormonal method, 66% were willing to use one afterwards (p = 0.006). Conclusion: Reproductive health education needs to be improved so that couples use reliable contraceptive methods appropriately. Although women are generally satisfied with the care received during abortion, they would prefer better accessibility to the procedure and more comprehensive information about the process from a neutral stance.

Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.

Trends of incidence, mortality and survival of multiple myeloma in Spain. A twenty-three-year population-based study.

BACKGROUND: Despite major advances, multiple myeloma remains an incurable disease. Epidemiological data from high-quality population-based registries are needed to understand the heterogeneous landscape of the disease. METHODS: Incidence, mortality and survival in multiple myeloma were comprehensively analyzed in the Girona and Granada population-based cancer registries, over a 23-year study (1994-2016), divided into three periods (1994-2001, 2002-2009 and 2010-2016). Joinpoint regression analysis was used to estimate the annual percentage change in incidence and mortality. Age-standardized net survival was calculated with the Pohar-Perme method. RESULTS: 1957 myeloma patients were included in the study, with a median age of 72 years. Age-standardized incidence and mortality rates decreased over time in both sexes and both rates were higher in males. Five-year age-standardized net survival by period was 27.4% (1994-2001), 38.8% (2002-2009), and 47.4% (2010-2016). Survival improved for all age groups: 32.4%, 74.1% and 78.5% for patients aged 15-49; 27.5%, 44.6%, and 58.5% for those aged 50-69; finally, 24.8%, 25.5%, and 26.3% for the older group. CONCLUSION: Incidence remained overall stable throughout the study, with only a small increase for men. Mortality was progressively decreasing in both sexes. Both incidence and mortality were higher in men. Age plays a critical role in survival, with impressive improvement in patients younger than 70 years, but only a minor benefit in those older than 70.

Serum levels of non-persistent environmental pollutants and risk of incident hypertension in a sub-cohort from the EPIC study.

BACKGROUND: The prevalence of arterial hypertension (AHT), a well-known risk factor for cardiovascular disease, has considerably increased over last decades. Non-persistent environmental pollutants (npEPs) are a group of ubiquitous chemicals, widely used in consumer products such as food packaging and cosmetics, which have been identified as endocrine disrupting chemicals and obesogens. The aim of this study was to assess the potential associations of serum levels of three groups of npEPs with the risk of incident AHT. METHODS: Cohort study within a sub-cohort of Granada EPIC-Spain center (n = 670). We quantified serum concentrations of three groups of npEPs, i.e., bisphenol A (BPA), four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP), and two benzophenones: benzophenone 1 (BP1), benzophenone 3 (BP3), in samples collected at recruitment. Statistical analyses were performed by means of Cox Proportional Hazard Models. RESULTS: Median follow-up time was 23 years. BPA and MP were found in >80% of the study population. Individuals within the 4th PP quartile (0.53-9.24 ng/ml) showed a statistically significant increased risk of AHT (HR = 1.40, p = 0.015). No associations were found for the rest of pollutants. CONCLUSIONS: Overall, we evidenced no associations of most npEPs with AHT risk, with the exception of an increased risk in the highest PP percentiles. Considering the limitations of using one spot serum sample for exposure characterization, further research on the potential contribution of npEPs on the development of AHT risk is warranted.

Phenotypic and genetic analysis of reproductive traits in horse populations with different breeding purposes.

Reproductive traits have a major influence on the economic effectiveness of horse breeding. However, there is little information available. We evaluated the use of reproductive traits as selection criteria in official breeding programs to increase the reproductive efficiency of breeding studs, analysing 696 690 records from the pedigree data of eight Spanish horse populations, with different breeding purposes. The reproductive parameters studied in both sexes were age at first foaling (AFF), age at last foaling, average reproductive life and generational interval. In the females, the average interval between foaling (AIF) and interval between first and second foaling were also studied. There were clear differences between sexes and breeds, which may be due to management practices, breeding purposes and the status of the populations, rather than to differences in actual physiological conditions. Riding mares were the most precocious (AFF, 1937.64 to 2255.69 days) and had a more intensive reproductive use (AIF, 625.83 to 760.07 days), whereas sires used for meat production were the most precocious males (AFF, 1789.93 to 1999.75 days), although they had a shorter reproductive life (1564.34 to 1797.32 days). Heritabilities (0.02 to 0.42 in females and 0.04 to 0.28 in males) evidenced the genetic component of the reproductive traits, with Sport Horses having the higher average values. These results support the selection by AFF to improve reproductive aspects because of its medium-high heritability and its positive correlations with other important reproductive traits. The inclusion of the AIF is also recommended in sport populations, because this determines the length of the breaks between foaling and conditions the reproductive performance of the dams, as well as their selective intensity, genetic gain and genetic improvement. It is therefore an important economic parameter in breeding studs.

Selective activation of memristive interfaces in TaO x -based devices by controlling oxygen vacancies dynamics at the nanoscale.

The development of novel devices for neuromorphic computing and non-traditional logic operations largely relies on the fabrication of well controlled memristive systems with functionalities beyond standard bipolar behavior and digital ON-OFF states. In the present work we demonstrate for Ta2O5-based devices that it is possible to selectively activate/deactivate two series memristive interfaces in order to obtain clockwise or counter-clockwise multilevel squared remanent resistance loops, just by controlling both the electroforming process and the (a)symmetry of the applied stimuli, and independently of the nature of the used metallic electrodes. Based on our thorough characterization, analysis and modeling, we show that the physical origin of this electrical behavior relies on controlled oxygen vacancies electromigration between three different nanoscopic zones of the active Ta2O5-x layer: a central one and two quasi-symmetric interfaces with reduced TaO2-h(y) layers. Our devices fabrication process is rather simple as it implies the room temperature deposition of only one CMOS compatible oxide-Ta-oxide-and one metal, suggesting that it might be possible to take advantage of these properties at low cost and with easy scability. The tunable opposite remanent resistance loops circulations with multiple-analogic-intermediate stable states allows mimicking the adaptable synaptic weight of biological systems and presents potential for non-standard logic devices.

Characterization and mobilization of toxic metals from electrolytic zinc waste.

The natural and forced mobilization of lead, cadmium and arsenic in zinc hydrometallurgy waste is studied with the purpose of establishing potentially environmentally damaging levels and associated risks in uncontrolled situations. Differential X-Ray diffraction is used to study, in simulated environmental situations, the relevant role played by several mineralogical and amorphous phases. The study of potential mobility shows that all the samples considered are susceptible of releasing a significant amount of potentially toxic elements (PTEs) depending of the particular environmental conditions. Two situations can be considered the most problematic: the natural mobilization of the released cadmium and zinc as a result of rain, and a change in the redox conditions caused by an anoxic environment (flooding and/or incorporation of organic matter). The presence of massive quantities of soluble salts increases the hazard potential of these residues, mobilizing the PTEs and creating a potential carcinogenic risk caused by a possible oral intake for both children and adults.

The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition.

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.

Spatial and temporal variations in Spain in the standardised ratio of in-hospital mortality due to colorectal cancer, 2008-2014.

BACKGROUND: Colorectal cancer (CRC) is the second cause of tumour mortality in Spain and Europe. To date, no studies have been conducted in Spain to evaluate the spatial and temporal distribution of the excess risk of death during hospitalisation for CRC. METHODS: A cohort was constructed of all episodes of hospitalisation in Spain due to CRC (codes 153 and 154 of the International Classification of Diseases, 9th edition, Clinical Modification) during the period 2008-2014, based on the minimum basic data set published by the Ministry of Health. Mortality ratios were calculated per region for each of the years analyzed (spatial or cross-sectional analysis) and during the overall study period, for each region independently (temporal or longitudinal analysis). In the first of these analyses, particular note was taken of the regions and years in which the limits of two and three standard deviations were exceeded. RESULTS: Two hundred and fifty eight thousand, nine hundred and twenty seven episodes of CRC were analysed. The patients were predominantly male (60.6%), with an average hospital stay of 13.16 days. Half underwent surgery during admission and on average presented more than six diagnoses at discharge. The spatial analysis revealed mortality ratios that deviated by at least three standard deviations in the following regions: Islas Canarias, Asturias, Valencia, Extremadura, País Vasco and Andalucía. The longitudinal analysis showed that most regions presented one or more years when CRC mortality was at least 15% higher than expected during the period; outstanding in this respect were Asturias, Navarra and La Rioja, where this excess risk was detected in at least 2 years. CONCLUSIONS: Geographic and temporal patterns of the distribution of the excess risk of mortality from CRC in Spain are described using SMRs. We conclude that during the study period, the geographic pattern of mortality in Spain did not coincide with the excess risk of mortality calculated using the SMR method described by Jarman and Foster. This method of risk estimation can be a useful tool for the study of mortality risk and its spatial variations.

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.

Importance of ocular electrophysiology in the diagnosis of retinal dystrophies. / Importancia de la electrofisiología ocular en el diagnóstico de las distrofias retinianas.

BACKGROUND AND OBJECTIVE: The diagnosis of retinal dystrophies is complex and is based on complete ophthalmological study, genetic study and electrophysiological studies (EPS). In this study, we intend to evaluate the role of electrophysiological and medical tests in the diagnosis of retinal dystrophies. MATERIAL AND METHODS: A retrospective observational study was conducted on 50 selected patients that attended the Neurophysiology Department of the University Hospital Virgen Macarena. An analysis was made of the variables that included, gender, age, referral hospital, reason for which the EPS was requested, applied EPS, genetic study, presumed diagnosis, and definitive diagnosis after EPS. A classification system was subsequently developed, which gives each case a value between 0 and 2, depending on the contribution of the electrophysiological tests to the final diagnosis. RESULTS: The mean age was 44.34 ±18.03 years (60% women). Retinitis pigmentosa (24%), optic neuropathy (12%), and Stargardt's disease (8%) were the most frequent diagnoses. The EPS modified the presumed diagnosis in 48% of the cases, confirmed the diagnosis in 44%, and did not provide any useful information in 8%. The contribution of the EPS was greater in patients seen in the HUVM and when requested by findings in the examination (P=.001). The false positives in the diagnosis of retinal dystrophy were 60% in patients not evaluated by the University Hospital Virgen Macarena. CONCLUSIONS: Electrophysiological test and specialised management of patients with retinal dystrophies play an important role in the diagnosis of these conditions.

Patient, tumor, and healthcare factors associated with regional variability in lung cancer survival: a Spanish high-resolution population-based study.

PURPOSE: The third most frequently diagnosed cancer in Europe in 2018 was lung cancer; it is also the leading cause of cancer death in Europe. We studied patient and tumor characteristics, and patterns of healthcare provision explaining regional variability in lung cancer survival in southern Spain. METHODS: A population-based cohort study included all 1196 incident first invasive primary lung cancer (C33-C34 according to ICD-10) cases diagnosed between 2010 and 2011 with follow-up until April 2015. Data were drawn from local population-based cancer registries and patients' hospital medical records from all public and private hospitals from two regions in southern Spain. RESULTS: There was evidence of regional differences in lung cancer late diagnosis (58% stage IV in Granada vs. 65% in Huelva, p value < 0.001). Among patients with stage I, only 67% received surgery compared with 0.6% of patients with stage IV. Patients treated with a combination of radiotherapy, chemotherapy, and surgery had a 2-year mortality risk reduction of 94% compared with patients who did not receive any treatment (excess mortality risk 0.06; 95% CI 0.02-0.16). Geographical differences in survival were observed between the two regions: 35% vs. 26% at 1-year since diagnosis. CONCLUSIONS: The observed geographic differences in survival between regions are due in part to the late cancer diagnosis which determines the use of less effective therapeutic options. Results from our study justify the need for promoting lung cancer early detection strategies and the harmonization of the best practice in lung cancer management and treatment.

Night-shift work and breast and prostate cancer risk: updating the evidence from epidemiological studies.

It has been hypothesized that circadian disruption is related to higher cancer risk. Since the International Agency for Research on Cancer classified shift work involving circadian disruption as probably carcinogenic to humans (Group 2A), multiple studies have been conducted to test this hypothesis. The aim of this systematic review was to summarize the findings and evaluate the quality of existing epidemiological studies (case-control and cohort studies) on the relationship between night-shift work and breast and prostate cancer risk. Thirty-three epidemiological studies investigating the relationship between night-shift work and breast (n = 26) or prostate (n = 8) cancer risk were included (one paper included both sites). The Newcastle-Ottawa Scale for the quality of non-randomized studies was used to assess the risk of bias of the publications. The studies included were heterogeneous regarding population (general population, nurses working in rotating shifts, and other) and measurement of exposure to night-shift work (ever vs. never exposure, short vs. long-term, rotating vs. permanent) and, thus, a diversity of outcomes were observed even within the same type of cancer. In summary, 62.5% works found some type of association between night-shift work and increased risk of cancer, for both breast and prostate. The risk of bias scored an average of 7.5 over 9 stars. Due to the limitations inherent in these studies, the evidence of a possible association between night-shift work and breast or prostate cancer risk remains uncertain and more studies providing greater control of exposure and confounding factors are required. Despite the lack of conclusive evidence, application of the precautionary principle seems advisable.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.