IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
Molecular Epidemiology of Tumour Promotion in Normal Kidney Tissues Across Populations
DE CARVALHO A. 1, ABEDI-ARDEKANI B. 1, CATTIAUX T. 1, CALVET F. 2, BLANCO R. 2, MARDAMSHINA M. 3, GABORIEAU V. 1, CHOPARD P. 1, NIKMANESH A. 1, PINHEIRO M. 2, SAMPER N. 2, LÓPEZ-ARRIBILLAGA E. 2, MARTINEZ CASALS A. 3, LUNDBERG E. 3, GONZALEZ-PEREZ A. 2, LOPEZ-BIGAS N. 2, BRENNAN P. 1, THE MUTOGRAPHS AND PROMINENT CONSORTIA o. 1
1 International Agency for Research on Cancer, Lyon, France; 2 Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; 3 Stanford University, Stanford, United States
Background
Renal cell carcinoma (RCC) accounts for ~2.4% of cancers worldwide, with up to ten-fold variation in incidence across countries. Clear cell RCC (ccRCC) represents 75–80% of cases, and obesity, hypertension, and smoking are established risk factors. However, data from the Mutographs project showed no mutational signatures associated with obesity or hypertension1, suggesting these exposures may act through non-mutagenic mechanisms. PROMINENT is a Cancer Grand Challenge project that extends mutational epidemiology to investigate how environmental and lifestyle exposures shape early clonal and tissue organization prior to malignancy in different human tissues.
Objectives
The PROMINENT kidney study aims to test whether obesity and hypertension promote RCC by reshaping clonal architecture, tissue microenvironment, and cellular phenotypes in histologically normal kidney. A key objective is to identify exposure-associated molecular and spatial alterations in non-tumour tissues that may serve as early biomarkers of tumour promotion and inform risk stratification.
Methods
The study includes RCC patients from nine countries spanning different incidence regions (Czechia, Lithuania, Russia, Canada, Romania, Serbia, Brazil, and Thailand). Biological samples, together with detailed epidemiological and clinical data, were collected through the Mutographs international network of recruiting centres and stored in the Genomic Epidemiology Branch biorepository2. Normal kidney tissues were selected based on body mass index and hypertension status, defining four exposure groups (high BMI with hypertension, high BMI only, hypertension only, and neither), and were balanced by incidence region, age, sex, and smoking status. Samples are being analysed using duplex sequencing to quantify mutational burden and positive selection, bulk RNA sequencing to assess exposure-associated transcriptional signatures, and spatial proteomics to capture early microenvironmental changes.
Results
Sample selection and processing were led by our team, considering different incidence regions and exposure profiles to the suspected promoters (i.e., obesity and hypertension). Laser-capture microdissection was performed to enrich for renal tubules, the cells of origin of ccRCC. Nearly 100 cases have undergone duplex and bulk RNA sequencing, and 40 have been analysed by spatial proteomics. Molecular, spatial, imaging, and epidemiological data are now being integrated to assess whether consistent tissue and clonal phenotypes of promotion can be detected in normal kidney tissue prior to malignant transformation and if these changes are driven by the presence of the explored risk factors.
Conclusions and Implications
By integrating mutational epidemiology with spatial and phenotypic profiling across diverse international populations, including LMIC settings, PROMINENT aims to define early molecular markers of tumour promotion that may inform population-level risk stratification and prevention strategies for RCC.