Browsing by Subject "EPIC"

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  • Smyth, L. J.; Kilner, J.; Nair, V.; Liu, H.; Brennan, E.; Kerr, K.; Sandholm, N.; Cole, J.; Dahlström, E.; Syreeni, A.; Salem, R. M.; Nelson, R. G.; Looker, H. C.; Wooster, C.; Anderson, K.; McKay, G. J.; Kee, F.; Young, I.; Andrews, D.; Forsblom, C.; Hirschhorn, J. N.; Godson, C.; Groop, P. H.; Maxwell, A. P.; Susztak, K.; Kretzler, M.; Florez, J. C.; McKnight, A. J. (2021)
    Background: A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10–8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Results: Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Conclusions: Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.
  • Smyth, L. J; Kilner, J.; Nair, V.; Liu, H.; Brennan, E.; Kerr, K.; Sandholm, N.; Cole, J.; Dahlström, E.; Syreeni, A.; Salem, R. M; Nelson, R. G; Looker, H. C; Wooster, C.; Anderson, K.; McKay, G. J; Kee, F.; Young, I.; Andrews, D.; Forsblom, C.; Hirschhorn, J. N; Godson, C.; Groop, P. H; Maxwell, A. P; Susztak, K.; Kretzler, M.; Florez, J. C; McKnight, A. J (BioMed Central, 2021)
    Abstract Background A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10–8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Results Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Conclusions Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.
  • Bradbury, Kathryn E.; Appleby, Paul N.; Tipper, Sarah J.; Travis, Ruth C.; Allen, Naomi E.; Kvaskoff, Marina; Overvad, Kim; Tjonneland, Anne; Halkjaer, Jytte; Cervenka, Iris; Mahamat-Saleh, Yahya; Bonnet, Fabrice; Kaaks, Rudolf; Fortner, Renee T.; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Stratigos, Alexander J.; Palli, Domenico; Grioni, Sara; Matullo, Giuseppe; Panico, Salvatore; Tumino, Rosario; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Ghiasvand, Reza; Veierod, Marit B.; Weiderpass, Elisabete; Bonet, Catalina; Molina, Elena; Huerta, Jose M.; Larranaga, Nerea; Barricarte, Aurelio; Merino, Susana; Isaksson, Karolin; Stocks, Tanja; Ljuslinder, Ingrid; Hemmingsson, Oskar; Wareham, Nick; Khaw, Kay-Tee; Gunter, Marc J.; Rinaldi, Sabina; Tsilidis, Konstantinos K.; Aune, Dagfinn; Riboli, Elio; Key, Timothy J. (2019)
    Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity >= 0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.
  • Zamora-Ros, Raul; Cayssials, Valerie; Jenab, Mazda; Rothwell, Joseph A.; Fedirko, Veronika; Aleksandrova, Krasimira; Tjonneland, Anne; Kyro, Cecilie; Overvad, Kim; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Mahamat-Saleh, Yahya; Kaaks, Rudolf; Kuehn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Valanou, Elissavet; Vasilopoulou, Effie; Masala, Giovanna; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Ricceri, Fulvio; Weiderpass, Elisabete; Lukic, Marko; Sandanger, Torkjel M.; Lasheras, Cristina; Agudo, Antonio; Sanchez, Maria-Jose; Amiano, Pilar; Navarro, Carmen; Ardanaz, Eva; Sonestedt, Emily; Ohlsson, Bodil; Nilsson, Lena Maria; Rutegard, Martin; Bueno-de-Mesquita, Bas; Peeters, Petra H.; Khaw, Kay-Thee; Wareham, Nicholas J.; Bradbury, Kathryn; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J.; Vineis, Paolo; Scalbert, Augustin (2018)
    Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2=1.06, 95% CI 0.99-1.14) or in men (HRlog2=0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2=0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HRlog2=1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.
  • Huseinovic, Ena; Winkvist, Anna; Freisling, Heinz; Slimani, Nadia; Boeing, Heiner; Buckland, Genevieve; Schwingshackl, Lukas; Olsen, Anja; Tionneland, Anne; Stepien, Magdalena; Boutron-Ruault, Marie-Christine; Mancini, Francesca; Artaud, Fanny; Kuehn, Tilman; Katzke, Verena; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Tumino, Rosario; Masala, Giovanna; Krogh, Vittorio; de Magistris, Maria Santucci; Ocke, Marga C.; Brustad, Magritt; Jensen, Torill Enget; Skeie, Guri; Rodriguez-Barranco, Miguel; Maria Huerta, Jose; Ardanaz, Eva; Ramon Quiros, Jose; Jakszyn, Paula; Sonestedt, Emily; Ericson, Ulrika; Wennberg, Maria; Key, Timothy J.; Aune, Dagfinn; Riboli, Elio; Weiderpass, Elisabete; Forslund, Helene Berteus (2019)
    Objective To examine timing of eating across ten European countries. Design Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake. Setting Ten Western European countries. Subjects In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020). Results A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0 center dot 68 (France) to 1 center dot 39 (Norway) among women, and from 0 center dot 71 (Greece) to 1 center dot 35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P