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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?

Park J 1 , Choi JY 1 , Choi J 2 , Chung S 1 , Song N 3 , Park SK 1 Show all authors , Han W 4 , Noh DY 4 , Ahn SH 5 , Lee JW 5 , Kim MK 6 , Jee SH 7 , Wen W 8 , Bolla MK 9 , Wang Q 9 , Dennis J 9 , Michailidou K 9 , Shah M 10 , Conroy DM 10 , Harrington PA 10 , Mayes R 10 , Czene K 11 , Hall P 11 , Teras LR 12 , Patel AV 13 , Couch FJ 13 , Olson JE 14 , Sawyer EJ 15 , Roylance R 16 , Bojesen SE 17 , Flyger H 18 , Lambrechts D 19 , Baten A 20 , Matsuo K 21 , Ito H 22 , Guénel P 23 , Truong T 23 , Keeman R 24 , Schmidt MK 24 , Wu AH 25 , Tseng CC 25 , Cox A 26 , Cross SS 27 , kConFab Investigators 28 , Andrulis IL 29 , Hopper JL 30 , Southey MC 31 , Wu PE 32 , Shen CY 33 , Fasching PA 34 , Ekici AB 35 , Muir K 36 , Lophatananon A 36 , Brenner H 37 , Arndt V 37 , Jones ME 38 , Swerdlow AJ 38 , Hoppe R 39 , Ko YD 40 , Hartman M 41 , Li J 42 , Mannermaa A 43 , Hartikainen JM 43 , Benitez J 44 , González-Neira A 45 , Haiman CA 25 , Dörk T 46 , Bogdanova NV 46 , Teo SH 47 , Mohd Taib NA 48 , Fletcher O 49 , Johnson N 49 , Grip M 50 , Winqvist R 51 , Blomqvist C 52 , Nevanlinna H 53 , Lindblom A 54 , Wendt C 55 , Kristensen VN 56 , Nbcs Collaborators 56 , Tollenaar RAEM 57 , Heemskerk-Gerritsen BAM 58 , Radice P 59 , Bonanni B 60 , Hamann U 61 , Manoochehri M 61 , Lacey JV 62 , Martinez ME 63 , Dunning AM 10 , Pharoah PDP 9 , Easton DF 9 , Yoo KY 64 , Kang D 1

Affiliations 

  • 1 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
  • 2 Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul 03080, Korea
  • 3 College of Pharmacy, Chungbuk National University, Cheongju-si 28160, Korea
  • 4 Cancer Research Institute, Seoul National University, Seoul 03080, Korea
  • 5 Department of Surgery, Medicine and ASAN Medical Center, University of Ulsan College, Seoul 05505, Korea
  • 6 Division of Cancer Epidemiology and Management, National Cancer Center, Goyang-si 10408, Korea
  • 7 Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 03722, Korea
  • 8 Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
  • 9 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0SR, UK
  • 10 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
  • 11 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 65 Stockholm, Sweden
  • 12 Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA
  • 13 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
  • 14 Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
  • 15 School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London SE1 9RT, UK
  • 16 Department of Oncology, UCLH Foundation Trust, London NW1 2PG, UK
  • 17 Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
  • 18 Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
  • 19 VIB Center for Cancer Biology, 3001 Leuve, Belgium
  • 20 Department of Radiotherapy Oncology, KU Leuven-University of Leuven, University Hospitals Leuven, 3000 Leuven, Belgium
  • 21 Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
  • 22 Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
  • 23 Center for Research in Epidemiology and Population Health (CESP), Team Exposome and Heredity, INSERM, University Paris-Saclay, 94805 Villejuif, France
  • 24 Division of Molecular Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands
  • 25 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
  • 26 Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2TN, UK
  • 27 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK
  • 28 Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia
  • 29 Fred A, Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
  • 30 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia
  • 31 Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia
  • 32 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
  • 33 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
  • 34 Department of Medicine Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
  • 35 Institute of Human Genetics, Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany
  • 36 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
  • 37 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 38 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK
  • 39 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany
  • 40 Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53177 Bonn, Germany
  • 41 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore
  • 42 Human Genetics Division, Genome Institute of Singapore, Singapore 138672, Singapore
  • 43 Translational Cancer Research Area, University of Eastern Finland, 70210 Kuopio, Finland
  • 44 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain
  • 45 Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain
  • 46 Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany
  • 47 Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya 47500, Malaysia
  • 48 Breast Cancer Research Unit, University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
  • 49 The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW7 3RP, UK
  • 50 Department of Surgery, Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
  • 51 Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, 90570 Oulu, Finland
  • 52 Department of Oncology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland
  • 53 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland
  • 54 Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
  • 55 Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 118 83 Stockholm, Sweden
  • 56 Department of Medical Genetics, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway
  • 57 Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
  • 58 Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 CN Rotterdam, The Netherlands
  • 59 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), 20133 Milan, Italy
  • 60 Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
  • 61 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
  • 62 Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA 91010, USA
  • 63 Moores Cancer Center, University of California San Diego, La Jolla, CA 92037, USA
  • 64 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea
Cancers (Basel), 2021 May 14;13(10).
PMID: 34069208 DOI: 10.3390/cancers13102370

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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