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)
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
BMC Cancer 2009, 9:257 doi:10.1186/1471-2407-9-257Published: 29 July 2009
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).
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.
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.
Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.