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. 2009 Jul 29:9:257.
doi: 10.1186/1471-2407-9-257.

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 Canzian  1 , Rudolf Kaaks, David G Cox, Katherine D Henderson, Brian E Henderson, Christine Berg, Sheila Bingham, Heiner Boeing, Julie Buring, Eugenia E Calle, Stephen Chanock, Francoise Clavel-Chapelon, Laure Dossus, Heather Spencer Feigelson, Christopher A Haiman, Susan E Hankinson, Robert Hoover, David J Hunter, Claudine Isaacs, Per Lenner, Eiliv Lund, Kim Overvad, Domenico Palli, Celeste Leigh Pearce, Jose R Quiros, Elio Riboli, Daniel O Stram, Gilles Thomas, Michael J Thun, Dimitrios Trichopoulos, Carla H van Gils, Regina G Ziegler
Affiliations

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 Canzian et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
Haploview plot of the genomic region of GNRH1 (A) and GNRHR (B). From top to bottom: position of genes (boxes: exons, lines: introns), SNPs genotyped in the multiethnic panel, graphical representation of LD and block structure (darker color represents higher LD, numbers in the colored squares are percentage of LD, expressed as D', absence of number means D' = 100%).
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