Sự liên quan của những thay đổi trong methyl hóa DNA bạch cầu với việc tiêu thụ folate qua chế độ ăn và rượu trong nghiên cứu EPIC

Springer Science and Business Media LLC - Tập 11 - Trang 1-13 - 2019
F. Perrier1, V. Viallon1, S. Ambatipudi2,3, A. Ghantous2, C. Cuenin2, H. Hernandez-Vargas2, V. Chajès4, L. Baglietto5, M. Matejcic4,6, H. Moreno-Macias7, T. Kühn8, H. Boeing9, A. Karakatsani10,11, A. Kotanidou10,12, A. Trichopoulou10, S. Sieri, S. Panico13, F. Fasanelli14, M. Dolle15, C. Onland-Moret16, I. Sluijs16, E. Weiderpass17,18,19,20, J. R. Quirós21, A. Agudo22, J. M. Huerta23,24, E. Ardanaz23,24,25,26, M. Dorronsoro27, T. Y. N. Tong28, K. Tsilidis29, E. Riboli29, M. J. Gunter4, Z. Herceg2, P. Ferrari1, I. Romieu4
1Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC), World Health Organization, Lyon CEDEX 08, France
2Epigenetics Group, IARC, Lyon, France
3MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK
4Nutritional Epidemiology Group, IARC, Lyon, France
5Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
6Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, USA
7Universidad Autonoma Metropolitana, Mexico City, Mexico
8Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
9Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany
10Hellenic Health Foundation, Athens, Greece
112nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, Haidari, Greece
121st Department of Critical Care Medicine and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece
13Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
14Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
15National Institute of Public Health and the Environment (RIVM), Centre for Health Protection (pb12), Bilthoven, The Netherlands
16Department of Epidemiology, Julius Center Research Program Cardiovascular Epidemiology, Utrecht, The Netherlands
17Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway
18Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
19Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, University of Helsinki, Helsinki, Finland
20Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
21Public Health Directorate, Asturias, Spain
22Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
23Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
24CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
25Navarra Public Health Institute, Pamplona, Spain
26IdisNA, Navarra Institute for Health Research, Pamplona, Spain
27Public Health Direction and Biodonostia Research Institute and CIBERESP, Basque Regional Health Department, San Sebastian, Spain
28Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
29Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

Tóm tắt

Có bằng chứng ngày càng tăng cho thấy folate, một thành phần quan trọng của chuyển hóa một-carbon, điều chỉnh epigenome. Rượu, có thể làm gián đoạn sự hấp thụ folate, cũng được biết đến là ảnh hưởng đến epigenome. Chúng tôi đã điều tra mối liên hệ giữa chế độ ăn uống folate và lượng rượu tiêu thụ đối với mức độ methyl hóa DNA bạch cầu trong nghiên cứu Điều tra Châu Âu về Ung thư và Dinh dưỡng (EPIC). Hồ sơ methyl hóa DNA toàn bộ bộ gen bạch cầu tại khoảng 450.000 vị trí CpG đã được thu thập bằng Illumina HumanMethylation 450K BeadChip với khoảng 450 phụ nữ tham gia kiểm soát trong một nghiên cứu trường hợp - đối chứng về ung thư vú nằm trong tập đoàn EPIC. Sau khi xử lý dữ liệu bằng phân tích biến thế thay thế để giảm biến thiên hệ thống, các mối liên hệ giữa methyl hóa DNA với chế độ ăn uống folate và lượng rượu tiêu thụ, được đánh giá qua bảng hỏi chế độ ăn, đã được điều tra bằng các mô hình tuyến tính theo vị trí CpG. Các vùng cụ thể của methylome đã được khám phá bằng phân tích vùng methyl hóa khác nhau (DMR) và hồi quy lasso ghép (FL). Phân tích DMR kết hợp kết quả từ phân tích theo tính năng cho một nhiễm sắc thể cụ thể và sử dụng khoảng cách giữa các tính năng làm trọng số, trong khi hồi quy FL kết hợp hai hình phạt để khuyến khích tính khan hiếm của các tính năng đơn lẻ và sự khác biệt giữa hai tính năng liên tiếp. Sau khi điều chỉnh các kiểm định đa, việc tiêu thụ folate qua chế độ ăn không có liên quan với mức độ methyl hóa tại bất kỳ vị trí methyl hóa DNA nào, trong khi những liên kết yếu đã được quan sát giữa lượng rượu tiêu thụ và mức độ methyl hóa tại các vị trí CpG cg03199996 và cg07382687, với qval = 0.029 và qval = 0.048, tương ứng. Thú vị thay, phân tích DMR đã tiết lộ tổng cộng 24 và 90 vùng liên quan đến chế độ ăn folate và rượu, tương ứng. Đối với việc tiêu thụ rượu, 6 trong số 15 DMR có ý nghĩa nhất được xác định thông qua FL. Lượng rượu tiêu thụ có liên quan đến mức độ methyl hóa tại hai vị trí CpG. Bằng chứng từ phân tích DMR và FL cho thấy rằng folate qua chế độ ăn và lượng rượu tiêu thụ có thể liên quan đến các vùng gen với hoạt động ức chế u như các gen GSDMD và HOXA5. Những kết quả này phù hợp với giả thuyết rằng các cơ chế epigenetic đóng một vai trò trong mối quan hệ giữa folate và rượu, mặc dù cần có thêm các nghiên cứu để làm rõ tầm quan trọng của các cơ chế này trong ung thư.

Từ khóa

#Folate #alcohol #DNA methylation #epigenetics #EPIC study

Tài liệu tham khảo

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