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Open Access 01-12-2009 | 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)

Authors: Federico Canzian, 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

Published in: BMC Cancer | Issue 1/2009

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/257/prepub

Title: 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)
Authors: Federico Canzian
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
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-9-257

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Background

Methods

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