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Open Access Research article

Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

Federico Canzian1*, Rudolf Kaaks1, David G Cox2, Katherine D Henderson34, Brian E Henderson3, Christine Berg5, Sheila Bingham6, Heiner Boeing7, Julie Buring8, Eugenia E Calle9, Stephen Chanock5, Francoise Clavel-Chapelon10, Laure Dossus1, Heather Spencer Feigelson9, Christopher A Haiman3, Susan E Hankinson8, Robert Hoover5, David J Hunter2, Claudine Isaacs11, Per Lenner12, Eiliv Lund13, Kim Overvad14, Domenico Palli15, Celeste Leigh Pearce3, Jose R Quiros16, Elio Riboli17, Daniel O Stram3, Gilles Thomas5, Michael J Thun9, Dimitrios Trichopoulos18, Carla H van Gils19 and Regina G Ziegler5

Author Affiliations

1 German Cancer Research Center (DKFZ), Heidelberg, Germany

2 Harvard School of Public Health, Boston, MA, USA

3 University of Southern California, Los Angeles, CA, USA

4 Beckman Research Institute of the City of Hope National Medical Center, Duarte, CA, USA

5 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

6 MRC Dunn Human Nutrition Unit, Cambridge, UK

7 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

8 Harvard Medical School, Boston, MA, USA

9 American Cancer Society, Atlanta, GA, USA

10 INSERM, Institut Gustave Roussy, Villejuif, France

11 Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA

12 Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

13 Institute of Community Medicine, University of Tromsø, Tromsø, Norway

14 Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark

15 Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy

16 Public Health and Health Planning Directorate, Asturias, Spain

17 Imperial College, London, UK

18 Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece

19 Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands

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BMC Cancer 2009, 9:257  doi:10.1186/1471-2407-9-257

Published: 29 July 2009

Abstract

Background

Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3).

Methods

We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects.

Results

Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels.

Conclusion

Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.