Cancers (May 2021)
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
- JooYong Park,
- Ji-Yeob Choi,
- Jaesung Choi,
- Seokang Chung,
- Nan Song,
- Sue K. Park,
- Wonshik Han,
- Dong-Young Noh,
- Sei-Hyun Ahn,
- Jong Won Lee,
- Mi Kyung Kim,
- Sun Ha Jee,
- Wanqing Wen,
- Manjeet K. Bolla,
- Qin Wang,
- Joe Dennis,
- Kyriaki Michailidou,
- Mitul Shah,
- Don M. Conroy,
- Patricia A. Harrington,
- Rebecca Mayes,
- Kamila Czene,
- Per Hall,
- Lauren R. Teras,
- Alpa V. Patel,
- Fergus J. Couch,
- Janet E. Olson,
- Elinor J. Sawyer,
- Rebecca Roylance,
- Stig E. Bojesen,
- Henrik Flyger,
- Diether Lambrechts,
- Adinda Baten,
- Keitaro Matsuo,
- Hidemi Ito,
- Pascal Guénel,
- Thérèse Truong,
- Renske Keeman,
- Marjanka K. Schmidt,
- Anna H. Wu,
- Chiu-Chen Tseng,
- Angela Cox,
- Simon S. Cross,
- kConFab Investigators,
- Irene L. Andrulis,
- John L. Hopper,
- Melissa C. Southey,
- Pei-Ei Wu,
- Chen-Yang Shen,
- Peter A. Fasching,
- Arif B. Ekici,
- Kenneth Muir,
- Artitaya Lophatananon,
- Hermann Brenner,
- Volker Arndt,
- Michael E. Jones,
- Anthony J. Swerdlow,
- Reiner Hoppe,
- Yon-Dschun Ko,
- Mikael Hartman,
- Jingmei Li,
- Arto Mannermaa,
- Jaana M. Hartikainen,
- Javier Benitez,
- Anna González-Neira,
- Christopher A. Haiman,
- Thilo Dörk,
- Natalia V. Bogdanova,
- Soo Hwang Teo,
- Nur Aishah Mohd Taib,
- Olivia Fletcher,
- Nichola Johnson,
- Mervi Grip,
- Robert Winqvist,
- Carl Blomqvist,
- Heli Nevanlinna,
- Annika Lindblom,
- Camilla Wendt,
- Vessela N. Kristensen,
- NBCS Collaborators,
- Rob A. E. M. Tollenaar,
- Bernadette A. M. Heemskerk-Gerritsen,
- Paolo Radice,
- Bernardo Bonanni,
- Ute Hamann,
- Mehdi Manoochehri,
- James V. Lacey,
- Maria Elena Martinez,
- Alison M. Dunning,
- Paul D. P. Pharoah,
- Douglas F. Easton,
- Keun-Young Yoo,
- Daehee Kang
Affiliations
- JooYong Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
- Ji-Yeob Choi
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
- Jaesung Choi
- Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul 03080, Korea
- Seokang Chung
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
- Nan Song
- College of Pharmacy, Chungbuk National University, Cheongju-si 28160, Korea
- Sue K. Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
- Wonshik Han
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea
- Dong-Young Noh
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea
- Sei-Hyun Ahn
- Department of Surgery, Medicine and ASAN Medical Center, University of Ulsan College, Seoul 05505, Korea
- Jong Won Lee
- Department of Surgery, Medicine and ASAN Medical Center, University of Ulsan College, Seoul 05505, Korea
- Mi Kyung Kim
- Division of Cancer Epidemiology and Management, National Cancer Center, Goyang-si 10408, Korea
- Sun Ha Jee
- Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 03722, Korea
- Wanqing Wen
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Manjeet K. Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
- Qin Wang
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
- Joe Dennis
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
- Kyriaki Michailidou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
- Mitul Shah
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
- Don M. Conroy
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
- Patricia A. Harrington
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
- Rebecca Mayes
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
- Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65 Stockholm, Sweden
- Per Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65 Stockholm, Sweden
- Lauren R. Teras
- Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA
- Alpa V. Patel
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
- Fergus J. Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
- Janet E. Olson
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
- Elinor J. Sawyer
- School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy’s Campus, King’s College London, London SE1 9RT, UK
- Rebecca Roylance
- Department of Oncology, UCLH Foundation Trust, London NW1 2PG, UK
- Stig E. Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
- Henrik Flyger
- Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
- Diether Lambrechts
- VIB Center for Cancer Biology, 3001 Leuve, Belgium
- Adinda Baten
- Department of Radiotherapy Oncology, KU Leuven—University of Leuven, University Hospitals Leuven, 3000 Leuven, Belgium
- Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
- Hidemi Ito
- Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
- Pascal Guénel
- Center for Research in Epidemiology and Population Health (CESP), Team Exposome and Heredity, INSERM, University Paris-Saclay, 94805 Villejuif, France
- Thérèse Truong
- Center for Research in Epidemiology and Population Health (CESP), Team Exposome and Heredity, INSERM, University Paris-Saclay, 94805 Villejuif, France
- Renske Keeman
- Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
- Marjanka K. Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
- Anna H. Wu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- Chiu-Chen Tseng
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- Angela Cox
- Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2TN, UK
- Simon S. Cross
- Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK
- kConFab Investigators
- Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia
- Irene L. Andrulis
- Fred A, Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
- John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia
- Melissa C. Southey
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia
- Pei-Ei Wu
- Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
- Chen-Yang Shen
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
- Peter A. Fasching
- Department of Medicine Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
- Arif B. Ekici
- Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany
- Kenneth Muir
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
- Artitaya Lophatananon
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Michael E. Jones
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK
- Anthony J. Swerdlow
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK
- Reiner Hoppe
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany
- Yon-Dschun Ko
- Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53177 Bonn, Germany
- Mikael Hartman
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore
- Jingmei Li
- Human Genetics Division, Genome Institute of Singapore, Singapore 138672, Singapore
- Arto Mannermaa
- Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland
- Jaana M. Hartikainen
- Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland
- Javier Benitez
- Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain
- Anna González-Neira
- Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
- Christopher A. Haiman
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
- Thilo Dörk
- Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany
- Natalia V. Bogdanova
- Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany
- Soo Hwang Teo
- Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya 47500, Malaysia
- Nur Aishah Mohd Taib
- Breast Cancer Research Unit, University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
- Olivia Fletcher
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW7 3RP, UK
- Nichola Johnson
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW7 3RP, UK
- Mervi Grip
- Department of Surgery, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
- Robert Winqvist
- Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, 90570 Oulu, Finland
- Carl Blomqvist
- Department of Oncology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland
- Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland
- Annika Lindblom
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
- Camilla Wendt
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 118 83 Stockholm, Sweden
- Vessela N. Kristensen
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway
- NBCS Collaborators
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway
- Rob A. E. M. Tollenaar
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Bernadette A. M. Heemskerk-Gerritsen
- Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 CN Rotterdam, The Netherlands
- Paolo Radice
- Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy
- Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
- Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Mehdi Manoochehri
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- James V. Lacey
- Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA 91010, USA
- Maria Elena Martinez
- Moores Cancer Center, University of California San Diego, La Jolla, CA 92037, USA
- Alison M. Dunning
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
- Paul D. P. Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
- Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
- Keun-Young Yoo
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea
- Daehee Kang
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
- DOI
- https://doi.org/10.3390/cancers13102370
- Journal volume & issue
-
Vol. 13,
no. 10
p. 2370
Abstract
In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
Keywords
