• Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE).

      Nagel, Gabriele; Stafoggia, Massimo; Pedersen, Marie; Andersen, Zorana J; Galassi, Claudia; Munkenast, Jule; Jaensch, Andrea; Sommar, Johan; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Krog, Norun H; Aamodt, Geir; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Fratiglioni, Laura; Sørensen, Mette; Tjønneland, Anne; Peeters, Petra H; Bueno-de-Mesquita, Bas; Vermeulen, Roel; Eeftens, Marloes; Plusquin, Michelle; Key, Timothy J; Concin, Hans; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Ranzi, Andrea; Cesaroni, Giulia; Forastiere, Francesco; Tamayo-Uria, Ibon; Amiano, Pilar; Dorronsoro, Miren; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole; Weinmayr, Gudrun (2018-04-26)
      Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancers of the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient air pollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-use regression models for particulate matter (PM) below 10 µm (PM10 ), below 2.5 µm (PM2.5 ), between 2.5 and 10 µm (PMcoarse ), PM2.5 absorbance and nitrogen oxides (NO2 and NOX ) as well as approximated by traffic indicators. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. During average follow-up of 14.1 years of 305 551 individuals, 744 incident cases of gastric cancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5 µg/m3 of PM2.5 was 1.38 (95%-CI 0.99;1.92) for gastric and 1.05 (95%-CI 0.62;1.77) for UADT cancers. No associations were found for any of the other exposures considered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influence markedly the effect estimate for PM2.5 and gastric cancer. Higher estimated risks of gastric cancer associated with PM2.5 was found in men (HR 1.98 (1.30;3.01)) as compared to women (HR 0.85 (0.5;1.45)). This large multicentre cohort study shows an association between long-term exposure to PM2.5 and gastric cancer, but not UADT cancers, suggesting that air pollution may contribute to gastric cancer risk. This article is protected by copyright. All rights reserved.
    • Ambient air pollution and primary liver cancer incidence in four European cohorts within the ESCAPE project.

      Pedersen, Marie; Andersen, Zorana J; Stafoggia, Massimo; Weinmayr, Gudrun; Galassi, Claudia; Sørensen, Mette; Eriksen, Kirsten T; Tjønneland, Anne; Loft, Steffen; Jaensch, Andrea; Nagel, Gabriele; Concin, Hans; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Ranzi, Andrea; Sokhi, Ranjeet; Vermeulen, Roel; Hoogh, Kees de; Wang, Meng; Beelen, Rob; Vineis, Paolo; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole (2017)
      Tobacco smoke exposure increases the risk of cancer in the liver, but little is known about the possible risk associated with exposure to ambient air pollution.
    • DNA methylation and exposure to ambient air pollution in two prospective cohorts.

      Plusquin, Michelle; Guida, Florence; Polidoro, Silvia; Vermeulen, Roel; Raaschou-Nielsen, Ole; Campanella, Gianluca; Hoek, Gerard; Kyrtopoulos, Soterios A; Georgiadis, Panagiotis; Naccarati, Alessio; Sacerdote, Carlotta; Krogh, Vittorio; Bas Bueno-de-Mesquita, H; Monique Verschuren, W M; Sayols-Baixeras, Sergi; Panni, Tommaso; Peters, Annette; Hebels, Dennie G A J; Kleinjans, Jos; Vineis, Paolo; Chadeau-Hyam, Marc (2017-11)
      Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N=613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value=0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.
    • The Influence of Meteorological Factors and Atmospheric Pollutants on the Risk of Preterm Birth.

      Giorgis-Allemand, Lise; Pedersen, Marie; Bernard, Claire; Aguilera, Inmaculada; Beelen, Rob M J; Chatzi, Leda; Cirach, Marta; Danileviciute, Asta; Dedele, Audrius; van Eijsden, Manon; Estarlich, Marisa; Fernández-Somoano, Ana; Fernández, Mariana F; Forastiere, Francesco; Gehring, Ulrike; Grazuleviciene, Regina; Gruzieva, Olena; Heude, Barbara; Hoek, Gerard; de Hoogh, Kees; van den Hooven, Edith H; Håberg, Siri E; Iñiguez, Carmen; Jaddoe, Vincent W V; Korek, Michal; Lertxundi, Aitana; Lepeule, Johanna; Nafstad, Per; Nystad, Wenche; Patelarou, Evridiki; Porta, Daniela; Postma, Dirkje; Raaschou-Nielsen, Ole; Rudnai, Peter; Siroux, Valérie; Sunyer, Jordi; Stephanou, Euripides; Sørensen, Mette; Eriksen, Kirsten Thorup; Tuffnell, Derek; Varró, Mihály J; Vrijkotte, Tanja G M; Wijga, Alet; Wright, John; Nieuwenhuijsen, Mark J; Pershagen, Göran; Brunekreef, Bert; Kogevinas, Manolis; Slama, Rémy (2017-02-15)
      Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure.
    • Long-term exposure to ambient air pollution and incidence of brain tumor: the European Study of Cohorts for Air Pollution Effects (ESCAPE).

      Andersen, Zorana J; Pedersen, Marie; Weinmayr, Gudrun; Stafoggia, Massimo; Galassi, Claudia; Jørgensen, Jeanette T; Sommar, Johan N; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Aasvang, Gunn Marit; Schwarze, Per; Pyko, Andrei; Pershagen, Göran; Korek, Michal; Faire, Ulf De; Östenson, Claes-Göran; Fratiglioni, Laura; Eriksen, Kirsten T; Poulsen, Aslak H; Tjønneland, Anne; Bräuner, Elvira Vaclavik; Peeters, Petra H; Bueno-de-Mesquita, Bas; Jaensch, Andrea; Nagel, Gabriele; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Migliore, Enrica; Vermeulen, Roel; Sokhi, Ranjeet; Keuken, Menno; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Cesaroni, Giulia; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole (2018-02-19)
      Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.
    • Long-Term Exposure to Ambient Air Pollution and Incidence of Postmenopausal Breast Cancer in 15 European Cohorts within the ESCAPE Project.

      Andersen, Zorana J; Stafoggia, Massimo; Weinmayr, Gudrun; Pedersen, Marie; Galassi, Claudia; Jørgensen, Jeanette T; Oudin, Anna; Forsberg, Bertil; Olsson, David; Oftedal, Bente; Aasvang, Gunn Marit; Aamodt, Geir; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Fratiglioni, Laura; Eriksen, Kirsten T; Tjønneland, Anne; Peeters, Petra H; Bueno-de-Mesquita, Bas; Plusquin, Michelle; Key, Timothy J; Jaensch, Andrea; Nagel, Gabriele; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Fournier, Agnes; Boutron-Ruault, Marie-Christine; Baglietto, Laura; Grioni, Sara; Marcon, Alessandro; Krogh, Vittorio; Ricceri, Fulvio; Sacerdote, Carlotta; Migliore, Enrica; Tamayo-Uria, Ibon; Amiano, Pilar; Dorronsoro, Miren; Vermeulen, Roel; Sokhi, Ranjeet; Keuken, Menno; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Cesaroni, Giulia; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole (2017)
      Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.
    • Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE).

      Fuks, Kateryna B; Weinmayr, Gudrun; Basagaña, Xavier; Gruzieva, Olena; Hampel, Regina; Oftedal, Bente; Sørensen, Mette; Wolf, Kathrin; Aamodt, Geir; Aasvang, Gunn Marit; Aguilera, Inmaculada; Becker, Thomas; Beelen, Rob; Brunekreef, Bert; Caracciolo, Barbara; Cyrys, Josef; Elosua, Roberto; Eriksen, Kirsten Thorup; Foraster, Maria; Fratiglioni, Laura; Hilding, Agneta; Houthuijs, Danny; Korek, Michal; Künzli, Nino; Marrugat, Jaume; Nieuwenhuijsen, Mark; Östenson, Claes-Göran; Penell, Johanna; Pershagen, Göran; Raaschou-Nielsen, Ole; Swart, Wim J R; Peters, Annette; Hoffmann, Barbara (2017-04-01)
      We investigated whether traffic-related air pollution and noise are associated with incident hypertension in European cohorts.
    • Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

      Gasull, Magda; Pumarega, José; Kiviranta, Hannu; Rantakokko, Panu; Raaschou-Nielsen, Ole; Bergdahl, Ingvar A; Sandanger, Torkjel Manning; Goñi, Fernando; Cirera, Lluís; Donat-Vargas, Carolina; Alguacil, Juan; Iglesias, Mar; Tjønneland, Anne; Overvad, Kim; Mancini, Francesca Romana; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Johnson, Theron; Kühn, Tilman; Trichopoulou, Antonia; Karakatsani, Anna; Peppa, Eleni; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Verschuren, Monique; Vermeulen, Roel; Rylander, Charlotta; Nøst, Therese Haugdahl; Rodríguez-Barranco, Miguel; Molinuevo, Amaia; Chirlaque, María-Dolores; Ardanaz, Eva; Sund, Malin; Key, Tim; Ye, Weimin; Jenab, Mazda; Michaud, Dominique; Matullo, Giuseppe; Canzian, Federico; Kaaks, Rudolf; Nieters, Alexandra; Nöthlings, Ute; Jeurnink, Suzanne; Chajes, Veronique; Matejcic, Marco; Gunter, Marc; Aune, Dagfinn; Riboli, Elio; Agudo, Antoni; Gonzalez, Carlos Alberto; Weiderpass, Elisabete; Bueno-de-Mesquita, Bas; Duell, Eric J; Vineis, Paolo; Porta, Miquel (2019-02-01)
      The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.
    • Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE).

      Weinmayr, Gudrun; Pedersen, Marie; Stafoggia, Massimo; Andersen, Zorana J; Galassi, Claudia; Munkenast, Jule; Jaensch, Andrea; Oftedal, Bente; Krog, Norun H; Aamodt, Geir; Pyko, Andrei; Pershagen, Göran; Korek, Michal; De Faire, Ulf; Pedersen, Nancy L; Östenson, Claes-Göran; Rizzuto, Debora; Sørensen, Mette; Tjønneland, Anne; Bueno-de-Mesquita, Bas; Vermeulen, Roel; Eeftens, Marloes; Concin, Hans; Lang, Alois; Wang, Meng; Tsai, Ming-Yi; Ricceri, Fulvio; Sacerdote, Carlotta; Ranzi, Andrea; Cesaroni, Giulia; Forastiere, Francesco; de Hoogh, Kees; Beelen, Rob; Vineis, Paolo; Kooter, Ingeborg; Sokhi, Ranjeet; Brunekreef, Bert; Hoek, Gerard; Raaschou-Nielsen, Ole; Nagel, Gabriele (2018-08-07)
      Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 μm (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults.