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).
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.


CONCLUSIONS
Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
Canzian
Federico
F
German Cancer Research Center (DKFZ), Heidelberg, Germany. f.canzian@dkfz.de
Kaaks
Rudolf
R
Cox
David G
DG
Henderson
Katherine D
KD
Henderson
Brian E
BE
Berg
Christine
C
Bingham
Sheila
S
Boeing
Heiner
H
Buring
Julie
J
Calle
Eugenia E
EE
Chanock
Stephen
S
Clavel-Chapelon
Francoise
F
Dossus
Laure
L
Feigelson
Heather Spencer
HS
Haiman
Christopher A
CA
Hankinson
Susan E
SE
Hoover
Robert
R
Hunter
David J
DJ
Isaacs
Claudine
C
Lenner
Per
P
Lund
Eiliv
E
Overvad
Kim
K
Palli
Domenico
D
Pearce
Celeste Leigh
CL
Quiros
Jose R
JR
Riboli
Elio
E
Stram
Daniel O
DO
Thomas
Gilles
G
Thun
Michael J
MJ
Trichopoulos
Dimitrios
D
van Gils
Carla H
CH
Ziegler
Regina G
RG
D001943:Breast Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005091:Exons; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D009361:Neoplasm Invasiveness; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011498:Protein Precursors / Q000235:genetics*; D011966:Receptors, LHRH / Q000235:genetics*; D044465:White People
C484844:GNRHR protein, human; D011498:Protein Precursors; D011966:Receptors, LHRH; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone