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).

TitleGenetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
Publication TypeJournal Article
Year of Publication2009
AuthorsCanzian, F, Kaaks, R, Cox, DG, Henderson, KD, Henderson, BE, Berg, C, Bingham, S, Boeing, H, Buring, J, Calle, EE, Chanock, S, Clavel-Chapelon, F, Dossus, L, Feigelson, HSpencer, Haiman, CA, Hankinson, SE, Hoover, R, Hunter, DJ, Isaacs, C, Lenner, P, Lund, iv, E, Overvad, K, Palli, D, Pearce, CLeigh, Quirós, JR, Riboli, E, Stram, DO, Thomas, G, Thun, MJ, Trichopoulos, D, van Gils, CH, Ziegler, RG
JournalBMC Cancer
Volume9
Pagination257
Date Published2009 Jul 29
ISSN1471-2407
KeywordsBreast Neoplasms, Cohort Studies, European Continental Ancestry Group, Exons, Female, Genetic Variation, Genotype, Gonadotropin-Releasing Hormone, Haplotypes, Humans, Neoplasm Invasiveness, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Prospective Studies, Protein Precursors, Receptors, LHRH
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.

DOI10.1186/1471-2407-9-257
Alternate JournalBMC Cancer
Citation Key10.1186/1471-2407-9-257
PubMed ID19640273
PubMed Central IDPMC2729775
Grant ListU01 CA098216 / CA / NCI NIH HHS / United States
U01 CA098710 / CA / NCI NIH HHS / United States
U01CA098233 / CA / NCI NIH HHS / United States
U01CA098758 / CA / NCI NIH HHS / United States