1. DNA methylome analysis identifies accelerated epigenetic aging associated with postmenopausal breast cancer susceptibility
- Author
-
Salvatore Panico, Ander Matheu Fernández, Françoise Clavel-Chapelon, Liacine Bouaoun, J. Ramón Quirós, Athena Sklias, Gianluca Severi, Elisabete Weiderpass, Myrto Barrdahl, Ruth C. Travis, Graham Byrnes, Paolo Vineis, Pagona Lagiou, Kim Overvad, Steve Horvath, Flavie Perrier, Antonia Trichopoulou, Rosario Tumino, Heiner Boeing, Therese Haugdahl Nøst, Laura Baglietto, Geoffroy Durand, Giovanna Masala, Pietro Ferrari, Elio Riboli, N. Charlotte Onland-Moret, Srikant Ambatipudi, Veronique Chajes, José María Huerta Castaño, Florence Le Calvez-Kelm, Cyrille Cuenin, Miguel Rodríguez-Barranco, Petra H.M. Peeters, Martijn E.T. Dollé, Androniki Naska, Claudia Agnoli, Torkjel M. Sandanger, Aurelio Barricarte, Silvia Polidoro, Antonio Agudo, Isabelle Romieu, Zdenko Herceg, Rudolf Kaaks, Hector Hernandez-Vargas, Marc J. Gunter, David C. Muller, University Medical Center Utrecht, Imperial College Trust, Ambatipudi, Srikant, Horvath, Steve, Perrier, Flavie, Cuenin, Cyrille, Hernandez Vargas, Hector, Le Calvez Kelm, Florence, Durand, Geoffroy, Byrnes, Graham, Ferrari, Pietro, Bouaoun, Liacine, Sklias, Athena, Chajes, Véronique, Overvad, Kim, Severi, Gianluca, Baglietto, Laura, Clavel Chapelon, Françoise, Kaaks, Rudolf, Barrdahl, Myrto, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Naska, Androniki, Masala, Giovanna, Agnoli, Claudia, Polidoro, Silvia, Tumino, Rosario, Panico, Salvatore, Dollé, Martijn, Peeters, Petra H. M, Onland Moret, N. Charlotte, Sandanger, Torkjel M, Nøst, Therese H, Weiderpass, Elisabete, Quirós, J. Ramón, Agudo, Antonio, Rodriguez Barranco, Miguel, Huerta Castaño, José María, Barricarte, Aurelio, Fernández, Ander Matheu, Travis, Ruth C, Vineis, Paolo, Muller, David C, Riboli, Elio, Gunter, Marc, Romieu, Isabelle, and Herceg, Zdenko
- Subjects
0301 basic medicine ,Oncology ,Adult ,Epigenomics ,medicine.medical_specialty ,Cancer Research ,Epigenomic ,Population ,Breast Neoplasms ,Biology ,Article ,Epigenesis, Genetic ,03 medical and health sciences ,Breast cancer ,Internal medicine ,Journal Article ,medicine ,Humans ,Genetic Predisposition to Disease ,Epigenetics ,Oncology & Carcinogenesis ,Prospective cohort study ,education ,Aged ,education.field_of_study ,DNA methylation ,VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 ,Age Factors ,Cancer ,Biomarker ,Middle Aged ,medicine.disease ,European Prospective Investigation into Cancer and Nutrition ,VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 ,Postmenopause ,030104 developmental biology ,Age acceleration ,Case-Control Studies ,Female ,Biomarkers ,Prospective studies ,1112 Oncology And Carcinogenesis - Abstract
Accepted manuscript version, licensed CC BY-NC-ND 4.0. Published version available in European Journal of Cancer, 75, 299-307. Aim of the study: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as ‘epigenetic clock’, has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Methods: Here, we profiled DNA methylation changes in a nested caseecontrol study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n Z 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. Results: We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007e1.076, P Z 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007e1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020e1.11, P Z 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD Z 1.20; 95 %CI: 1.03e1.40, P Z 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Conclusion: Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.
- Published
- 2017
- Full Text
- View/download PDF