Despite decades of concern over the carcinogenic potential of agricultural pesticides, toxicological studies relying on single endpoints have yet to establish a definitive link between environmental pesticide exposure and cancer in real-world contexts. Here we use an integrative spatial Bayesian framework that merges high-resolution environmental pesticide risk modelling with comprehensive cancer registry data to map pesticide-linked cancer clusters in Peru with unprecedented precision. Our process-based model, encompassing 31 key pesticide active ingredients, together with an innovative stratification of cancer cases by developmental lineage, reveals a robust spatial association between environmental pesticide exposure risk and cancer incidence. In pesticide-associated cancer hotspots, exposomic profiling of liver tissue-a primary target of chemical carcinogens-uncovers a distinct transcriptomic signature of pesticide exposure, implicating a non-genotoxic mode of action that disrupts core regulatory circuitries sustaining cell identity. Collectively, these findings strongly support a mechanistic link between pesticide exposure and cancer, challenging assumptions of human non-carcinogenicity derived from reductionist experimental models. This study redefines the exposome as a lineage-conditioned, mechanistically tractable framework and shows how complex pesticide mixtures can contribute to carcinogenic trajectories, with profound and far-reaching implications for global health policy and socio-ecological equity.

Background/Objectives: Primary intracranial sarcoma is a recognized entity within the World Health Organization Classification of Tumours of the Central Nervous System (CNS) and comprises an aggressive subgroup of mesenchymal, non-meningothelial neoplasms. Among these, tumours associated with DICER1 alterations have recently been characterized as a distinct molecular subset. Although globally rare, primary intracranial sarcomas consistent with the DICER1-associated spectrum demonstrate an unusually high incidence in Peru, where they represent the second most common high-grade pediatric CNS malignancy after medulloblastoma. This study aimed to describe their clinicopathological features and outcomes in a large national cohort. Methods: We retrospectively analyzed 112 pediatric cases diagnosed between 2011 and 2025 at the National Cancer Institute of Peru, integrating histopathology, immunohistochemistry and clinical outcomes. Results: The median age was 7 years, and most tumours were supratentorial, predominantly affecting the frontal and parietal lobes. Histologically, they exhibited spindle, pleomorphic and undifferentiated round cell patterns, with frequent hyaline globules and aberrant vasculature. Immunohistochemistry showed recurrent ATRX loss, p53 overexpression and high proliferative indices, whereas myogenic markers were variably expressed. Median overall survival was 25 months, with 12-, 36-and 60-month survival rates of 65.7%, 45.9% and 44.0%, respectively. None of the tested markers (ATRX, p53 and Ki-67) demonstrated prognostic significance. Conclusion: This is the largest pediatric series of DICER1-mutant primary intracranial sarcomas reported from a low-and middle-income country. The findings confirm their poor prognosis and biological heterogeneity, highlighting the urgent need for integrated molecular and epidemiological research to identify risk factors and improve patient outcomes.

Ampullary carcinoma (AC) is a rare epithelial cancer, representing around 0.2% of all gastrointestinal malignancies worldwide, with an estimated incidence of 0.73 per 100,000 people. The rarity of AC, combined with the intricate anatomy of its site of origin, often complicates histopathological diagnosis. Recent advances in molecular research, however, have begun to illuminate its underlying biological complexity. In this study, we present the first comprehensive single-cell transcriptomic atlas of AC, encompassing both malignant epithelial populations and the tumor immune microenvironment (TIME). We identified upregulation of oncogenic drivers previously linked to AC, along with an AC-specific transcriptional program featuring potential biomarkers for minimally invasive diagnostics. Furthermore, we characterized an immunosuppressive TIME, enriched in anti-inflammatory-like tumor-associated macrophages (TAMs) and T cell subsets with limited antitumor activity. Collectively, these findings provide a foundational resource for the identification and validation of candidate biomarkers for early detection and targeted therapies in AC.

BACKGROUND:Cognitive impairment related to chemotherapy-commonly referred to as "chemo brain"-is a well-documented phenomenon among breast cancer patients. These impairments affect memory, attention, executive function, and social cognition, yet remain understudied in low- and middle-income countries. In Peru, where populations present a high proportion of Amerindian ancestry and distinct sociocultural factors, evidence is scarce. METHODS:We conducted a longitudinal study of 143 Peruvian women aged 28-64 years, newly diagnosed with early-stage breast cancer and naïve to chemotherapy, treated at the National Institute of Neoplastic Diseases (INEN) in Lima. Cognitive function was assessed using the Addenbrooke's Cognitive Examination (ACE), the INECO Frontal Screening Test (IFS), and a Facial Emotion Recognition (FER) task to evaluate social cognition. Baseline tests were performed before the start of treatment for each patient, and post-treatment tests were performed every 3 months. Global genetic ancestry was estimated using the ADMIXTURE algorithm based on the Affymetrix Precision Medicine Research Array. RESULTS:Native American ancestry accounted for 77.8% of the study population. Post-chemotherapy assessments revealed cognitive impairment in 21% of patients based on FER, 15% on ACE, and 12% on IFS. Higher educational attainment was associated with better cognitive performance across all domains. CONCLUSION:Chemotherapy was associated with measurable cognitive decline in a subset of Peruvian breast cancer patients. Brief and culturally adaptable tools such as the FER test offer a promising approach for routine cognitive screening in oncology settings, particularly in resource-limited contexts. Incorporating these assessments into standard care may facilitate early detection and more personalized supportive interventions.

In the last three decades, DNA sequencing of ancient animal osteological assemblages has become an important tool complementing standard archaeozoological approaches to reconstruct the history of animal domestication. However, osteological assemblages of key archaeological contexts are not always available or do not necessarily preserve enough ancient DNA for a cost-effective genetic analysis. Here, we develop an in-solution target-enrichment approach, based on 80-mer species-specific RNA probes (ranging from 306 to 1686 per species) to characterise (in single experiments) the mitochondrial genetic variation from eight domesticated animal species of major economic interest: cattle, chickens, dogs, donkeys, goats, horses, pigs and sheep. We also illustrate how our design can be adapted to enrich DNA library content and map the Y-chromosomal diversity within Equus caballus. By applying our target-enrichment assay to an extensive panel of ancient osteological remains, farm soil, and cave sediments spanning the last 43 kyrs, we demonstrate that minimal sequencing efforts are necessary to exhaust the DNA library complexity and to characterise mitogenomes to an average depth-of-coverage of 19.4 to 2003.7-fold. Our assay further retrieved horse mitogenome and Y-chromosome data from Late Pleistocene coprolites, as well as bona fide mitochondrial sequences from species that were not part of the probe design, such as bison and cave hyena. Our methodology will prove especially useful to minimise costs related to the genetic analyses of maternal and paternal lineages of a wide range of domesticated and wild animal species, and for mapping their diversity changes over space and time, including from environmental samples.

This article highlights Peru's experience in establishing a national tumor bank network, serving as a model for low- and middle-income countries. Launched in 2005 at the National Institute of Neoplastic Diseases, efforts accelerated under the 2021 National Cancer Act, which formalized the National Tumor Bank and its integration with the National Oncology Network. This initiative connects tumor banks across regional cancer institutes, enabling systematic biological sample collection, particularly from underrepresented populations, such as those with high Amerindian ancestry. Ethical oversight, technical standards, and specialized management software ensure efficient data sharing and genomic research. The network supports cancer research through integration with the Population Cancer Registry, providing unique insights into cancer incidence and outcomes. To date, 5992 cases have been documented. Through international collaboration with Latin American countries, Peru provides a framework for inclusive cancer research, enriching global genomic datasets and strengthening research capacity in diverse and vulnerable populations.

BACKGROUND:Liver resection is the mainstay treatment option for patients with hepatocellular carcinoma in the non-cirrhotic liver (NCL-HCC), but almost half of these patients will experience a recurrence within five years of surgery. Therefore, we aimed to develop a rationale-based risk evaluation tool to assist surgeons in recurrence-related treatment planning for NCL-HCC. METHODS:We analyzed single-center data from 263 patients who underwent liver resection for NCL-HCC. Using machine learning modeling, we first determined an optimal cut-off point to discriminate early versus late relapses based on time to recurrence. We then constructed a risk score based on preoperative variables to forecast outcomes according to recurrence-free survival. RESULTS:We computed an optimal cut-off point for early recurrence at 12 months post-surgery. We identified macroscopic vascular invasion, multifocal tumor, and spontaneous tumor rupture as predictor variables of outcomes associated with early recurrence and integrated them into a scoring system. We thus stratified, with high concordance, three groups of patients on a graduated scale of recurrence-related survival. CONCLUSION:We constructed a preoperative risk score to estimate outcomes after liver resection in NCL-HCC patients. Hence, this score makes it possible to rationally stratify patients based on recurrence risk assessment for better treatment planning.

Introduction: Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Aim: Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. Methods: HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. Results: When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (> 90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. Conclusion: HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming. (c) 2023 Asociaci & oacute;n Mexicana de Gastroenterolog & iacute;a. Published by Masson Doyma M & eacute;xico S.A. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

En Perú, el carcinoma hepatocelular (CHC) ocupa el tercer lugar en incidencia entre los tumores del sistema digestivo, y tiene una alta tasa de mortalidad, 17.7 por 100,000 habitantes. La mayoría de los casos reportados no presentan la epidemiología clínica clásica del CHC observado en otras partes del mundo. Además, se ha identificado que estos pacientes presentan un perfil transcriptómico distinto y un proceso tumoral singular, sugiriendo un proceso particular de hepatocarcinogénesis en una fracción de la población peruana. El presente estudio busca comprender la implicancia clínica y biológica del perfil epigenético (metilación) y de expresión de los genes (transcriptómico) del CHC en los pacientes peruanos. Se evaluó el perfil de transcriptómico y de metilación de ADN de hígado y CHC en 74 pacientes peruanos. El agrupamiento por edades mostró una mayor metilación del ADN en los pacientes jóvenes con CHC, en contraste no se observaron diferencias en el perfil transcriptómico. Adicionalmente, también se evidenció una alta prevalencia del virus de hepatitis B (VHB) (> 90%) en los pacientes jóvenes con CHC. El análisis de enriquecimiento en ambos perfiles moleculares demostró que PRC2 es posiblemente uno de los principales actores moleculares en este proceso tumoral hepático en pacientes peruanos. El CHC peruano presenta un perfil molecular único, asociado a la presencia del VHB, y con una hipermetilación global del ADN asociado a células hepáticas indiferenciadas o a una reprogramación celular. Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (> 90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.

Pseudocereals are best known for three crops derived from the Andes: quinoa (Chenopodium quinoa), canihua (C. pallidicaule), and kiwicha (Amaranthus caudatus). Their grains are recognized for their nutritional benefits; however, there is a higher level of polyphenism. Meanwhile, the chemical food safety of pseudocereals remains poorly documented. Here, we applied untargeted and targeted metabolomics approaches by LC-MS to achieve both: i) a comprehensive chemical mapping of pseudocereal samples collected in the Andes; and ii) a quantifi-cation of their contents in emerging mycotoxins. An inventory of the fungal community was also realized to better know the fungi present in these grains. Metabotyping permitted to add new insights into the chemotax-onomy of pseudocereals, confirming the previously established phylotranscriptomic clades. Sixteen samples from Peru (out of 27) and one from France (out of one) were contaminated with Beauvericin, an emerging mycotoxin. Several mycotoxigenic fungi were detected, including Aspergillus sp., Penicillium sp., and Alternaria sp.

Background: It has previously been demonstrated that a fraction of patients with hepatocellular carcinoma (HCC) > 10 cm can benefit from liver resection. However, there is still a lack of effective decision making tools to inform intervention in these patients. Methods: We analysed a comprehensive set of clinical data from 234 patients who underwent liver resection for HCC >10 cm at the National Cancer Institute of Peru between 1990 and 2015, monitored their survival, and constructed a nomogram to predict the surgical outcome based on preoperative variables. Results: We identified cirrhosis, multifocality, macroscopic vascular invasion, and spontaneous tumour rupture as independent predictors of survival and integrated them into a nomogram model. The nomogram's ability to forecast survival at 1, 3, and 5 years was subsequently confirmed with high concordance using an internal validation. Through applying this nomogram, we stratified three groups of patients with different survival probabilities. Conclusion: We constructed a preoperative nomogram to predict long-term survival in patients with HCC >10 cm. This nomogram is useful in determining whether a patient with large HCC might truly benefit from liver resection, which is paramount in low-and middle-income countries where HCC is often diagnosed at advanced stages.

Objetivo. Determinar la relación entre la anemia y los síntomas de depresión en las pacientes con cáncer de mama en etapa temprana en el Instituto Nacional de Enfermedades Neoplásicas (INEN), Lima, Perú. Métodos. Se realizó un estudio observacional transversal analítico de 60 mujeres peruanas diagnosticadas con cáncer de mama en etapa temprana, estadios I y II, entre junio de 2019 y marzo de 2020. Todas las participantes fueron evaluadas por el puntaje del Inventario de depresión de Beck-II (BDI-II), no habían recibido quimioterapia previa y cumplían con los criterios de inclusión. Cada participante aportó una muestra de sangre que se utilizó para estimar la hemoglobina y el recuento de glóbulos rojos y blancos. Resultados. De las 60 pacientes que cumplieron los criterios de inclusión, veinte (33,3 %) tenían síntomas depresivos en el momento del diagnóstico. Los niveles medios de hemoglobina en las pacientes con síntomas de depresión (M = 10,9, SD = 2,1) fueron más bajos en comparación con los de las pacientes sin depresión (M = 13,6, SD =1, p = 0,004). Una limitación de nuestro estudio fue el pequeño tamaño de la muestra y el hecho de que no se analizaron las hormonas tiroideas y la vitamina B12. Conclusiones. Nuestro estudio encontró una diferencia signifcativa de niveles de hemoglobina entre pacientes con cáncer de mama con síntomas de depresión. Se necesitan intervenciones para abordar la presencia de anemia y depresión en mujeres con cáncer de mama para mejorar los resultados de salud en estas pacientes.

The Central Andes of Peru are a region of great concern regarding pesticide risk to the health of local communities. Therefore, we conducted an observational study to assess the level of pesticide contamination among Andean people. Analytical chemistry methods were used to measure the concentrations of 170 pesticide-related compounds in hair samples from 50 adult Andean subjects living in rural and urban areas. As part of the study, a questionnaire was administered to the subjects to collect information regarding factors that increase the risk of pesticide exposure. Our results indicate that Andean people are strongly exposed to agrochemicals, being contaminated with a wide array of pesticide-related compounds at high concentration levels. Multivariate analyses and geostatistical modeling identified sociodemographic factors associated with rurality and food origin that increase pesticide exposure risk. The present study represents the first comprehensive investigation of pesticide-related compounds detected in body samples collected from people living in the Central Andes of Peru. Our findings pinpoint an alarming environmental situation that threatens human health in the region and provide a rationale for improving public policies to protect local communities.

BackgroundThe COVID-19 pandemic has had a direct effect on patients with cancer, as reflected by the large number of COVID-19-related cancer deaths reported worldwide and the substantial decrease in cancer-related consultations during the pandemic. However, the impact of the COVID-19 pandemic on cancer mortality in Latin American countries has not been properly estimated. The aim of this study was to analyse the excess mortality related to cancer during the pandemic in Peru, including deaths directly or indirectly attributed to COVID-19.MethodsExcess mortality, which compares the number of deaths by any cause with the average number of expected deaths in typical circumstances during a specific timeframe, can be used as a simple but reliable indicator of the impact of the COVID-19 pandemic on cancer services. We carried out a descriptive study using data from the Peruvian death registration system, from which we filtered records that had registered neoplastic diseases (according to the tenth revision of WHO's International Statistical Classification of Diseases and Related Health Problems) as the cause of death between. Only data for the period of March 15 to June 30 in the years 2017–20 was included. We calculated excess mortality by subtracting the average number of deaths recorded for the indicated period between 2017 and 2019 from the same period of 2020 records (ie, the duration of lockdown measures in Peru) to obtain the percentage of excess mortality.FindingsThe percentage of changes in the number of cancer-related deaths in Peru was +13·90% from 2017 to 2018, –1·27% from 2018 to 2019, and +16·94% from 2019 to 2020. We found an excess mortality of 928 cases (corresponding to an excess mortality of +17·27%) among patients with cancer, when comparing years 2017–19 with the year 2020. During the lockdown in 2020, 3135 (58·4%) of 5372 cancer deaths happened at home (vs 5900 [44·2%] of 13 338 for the years 2017–19). The highest excess mortality percentage was observed in patients with prostate cancer (+50·43%), breast cancer (+33·62%), and leukaemia (32·78%). Although these findings appear to be in line with reports from other countries, only 184 (3·4%) of 5372 deaths were registered with COVID-19 as an additional cause of death.InterpretationOur results suggest that COVID-19 control measures (eg, lockdowns, physical distancing, and isolation of symptomatic patients), alongside the overwhelming strain on the health-care system, had a detrimental impact on cancer mortality in Peru. The pandemic has exposed flaws in the Peruvian health-care system, especially regarding cancer care. Although we recognise that the rate of COVID-19 testing in Peru is one of the lowest in Latin America, the excess of cancer deaths cannot be fully explained by COVID-19. These findings might be an indication that the alarming increase in cancer mortality in Peru could continue over the upcoming months if no action is taken. Our study also shows the importance of an adequate registry of deaths. We recommend that the national authorities should implement policies to limit the impact of the COVID-19 pandemic on patients with cancer, and that the continuous update and monitoring of deaths initiated during the COVID-19 pandemic is sustained. These measures can help to confirm the increasing trend in cancer deaths; serve as a rationale to develop strategies that can alleviate this burden (eg, by adopting models for delivering optimal cancer care while minimising transmission of COVID-19); and minimise the possibility of an increase in patients presenting with advanced-stage cancers.FundingInternational Joint Laboratories Programme of the French National Research Institute for Sustainable Development.

High prevalence of parasitic or bacterial infectious diseases in some world areas is due to multiple reasons, including a lack of an appropriate health policy, challenging logistics and poverty. The support to research and development of new medicines to fight infectious diseases is one of the sustainable development goals promoted by World Health Organization (WHO). In this sense, the traditional medicinal knowledge substantiated by ethnopharmacology is a valuable starting point for drug discovery. This work aims at the scientific validation of the traditional use of Piper species ("Cordoncillos") as firsthand anti-infectious medicines. For this purpose, we adapted a computational statistical model to correlate the LCMS chemical profiles of 54 extracts from 19 Piper species to their corresponding anti-infectious assay results based on 37 microbial or parasites strains. We mainly identified two groups of bioactive compounds (called features as they are considered at the analytical level and are not formally isolated). Group 1 is composed of 11 features being highly correlated to an inhibiting activity on 21 bacteria (principally Gram-positive strains), one fungus (C. albicans), and one parasite (Trypanosoma brucei gambiense). The group 2 is composed of 9 features having a clear selectivity on Leishmania (all strains, both axenic and intramacrophagic). Bioactive features in group 1 were identified principally in the extracts of Piper strigosum and P. xanthostachyum. In group 2, bioactive features were distributed in the extracts of 14 Piper species. This multiplexed approach provided a broad picture of the metabolome as well as a map of compounds putatively associated to bioactivity. To our knowledge, the implementation of this type of metabolomics tools aimed at identifying bioactive compounds has not been used so far.