Almudena Espín-Pérez1, Laia Font-Ribera2, Karin van Veldhoven3, Julian Krauskopf4, Lutzen Portengen5, Marc Chadeau-Hyam3, Roel Vermeulen5, Joan O Grimalt6, Cristina M Villanueva2, Paolo Vineis3, Manolis Kogevinas2, Jos C Kleinjans4, Theo M de Kok4. 1. Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. Electronic address: a.espin@maastrichtuniversity.nl. 2. Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. 3. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. 4. Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 5. Institute for Risk Assessment Sciences, Utrecht, The Netherlands. 6. Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona, Catalonia, Spain.
Abstract
BACKGROUND: Swimming in a chlorinated pool results in high exposure levels to disinfection by-products (DBPs), which have been associated with an increased risk of bladder cancer. OBJECTIVES: By studying molecular responses at the blood transcriptome level we examined the biological processes associated with exposure to these compounds. METHODS: Whole-genome gene expression and microRNA analysis was performed on blood samples collected from 43 volunteers before and 2h after 40min swimming in an indoor chlorinated pool (PISCINAII study). Exposure to THMs was measured in exhaled breath. Heart rate and kcal expenditure were measured as proxies for physical activity. Associations between exposure levels and gene expression were assessed using multivariate normal models (MVN), correcting for age, body mass index and sex. A Bonferroni threshold at 5% was applied. RESULTS: MVN-models for the individual exposures identified 1778 genes and 23 microRNAs that were significantly associated with exposure to at least one DBP. Due to co-linearity it was not possible to statistically disentangle responses to DBP exposure from those related to physical activity. However, after eliminating previously reported transcripts associated with physical activity a large number of hits remained associated with DBP exposure. Among those, 9 were linked with bladder and 31 with colon cancer. Concordant microRNA/mRNA expressions were identified in association with DBP exposure for hsa-mir-22-3p and hsa-miR-146a-5p and their targets RCOR1 and TLR4, both related to colon cancer in association with DBP exposure. CONCLUSIONS: Short-term exposure to low levels of DBPs shows genomics responses that may be indicative of increased cancer risk.
BACKGROUND: Swimming in a chlorinated pool results in high exposure levels to disinfection by-products (DBPs), which have been associated with an increased risk of bladder cancer. OBJECTIVES: By studying molecular responses at the blood transcriptome level we examined the biological processes associated with exposure to these compounds. METHODS: Whole-genome gene expression and microRNA analysis was performed on blood samples collected from 43 volunteers before and 2h after 40min swimming in an indoor chlorinated pool (PISCINAII study). Exposure to THMs was measured in exhaled breath. Heart rate and kcal expenditure were measured as proxies for physical activity. Associations between exposure levels and gene expression were assessed using multivariate normal models (MVN), correcting for age, body mass index and sex. A Bonferroni threshold at 5% was applied. RESULTS: MVN-models for the individual exposures identified 1778 genes and 23 microRNAs that were significantly associated with exposure to at least one DBP. Due to co-linearity it was not possible to statistically disentangle responses to DBP exposure from those related to physical activity. However, after eliminating previously reported transcripts associated with physical activity a large number of hits remained associated with DBP exposure. Among those, 9 were linked with bladder and 31 with colon cancer. Concordant microRNA/mRNA expressions were identified in association with DBP exposure for hsa-mir-22-3p and hsa-miR-146a-5p and their targets RCOR1 and TLR4, both related to colon cancer in association with DBP exposure. CONCLUSIONS: Short-term exposure to low levels of DBPs shows genomics responses that may be indicative of increased cancer risk.
Authors: Lucas A Salas; Emily R Baker; Mark J Nieuwenhuijsen; Carmen J Marsit; Brock C Christensen; Margaret R Karagas Journal: Environ Int Date: 2019-01-05 Impact factor: 9.621
Authors: Pooja Jain; Paolo Vineis; Benoît Liquet; Jelle Vlaanderen; Barbara Bodinier; Karin van Veldhoven; Manolis Kogevinas; Toby J Athersuch; Laia Font-Ribera; Cristina M Villanueva; Roel Vermeulen; Marc Chadeau-Hyam Journal: J Epidemiol Community Health Date: 2018-03-21 Impact factor: 3.710
Authors: Iro Evlampidou; Laia Font-Ribera; David Rojas-Rueda; Esther Gracia-Lavedan; Nathalie Costet; Neil Pearce; Paolo Vineis; Jouni J K Jaakkola; Francis Delloye; Konstantinos C Makris; Euripides G Stephanou; Sophia Kargaki; Frantisek Kozisek; Torben Sigsgaard; Birgitte Hansen; Jörg Schullehner; Ramon Nahkur; Catherine Galey; Christian Zwiener; Marta Vargha; Elena Righi; Gabriella Aggazzotti; Gunda Kalnina; Regina Grazuleviciene; Kinga Polanska; Dasa Gubkova; Katarina Bitenc; Emma H Goslan; Manolis Kogevinas; Cristina M Villanueva Journal: Environ Health Perspect Date: 2020-01-15 Impact factor: 9.031