Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).
Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.
Ahn
Jiyoung
J
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Schumacher
Fredrick R
FR
Berndt
Sonja I
SI
Pfeiffer
Ruth
R
Albanes
Demetrius
D
Andriole
Gerald L
GL
Ardanaz
Eva
E
Boeing
Heiner
H
Bueno-de-Mesquita
Bas
B
Chanock
Stephen J
SJ
Clavel-Chapelon
Françoise
F
Diver
W Ryan
WR
Feigelson
Heather Spencer
HS
Gaziano
J Michael
JM
Giovannucci
Edward
E
Haiman
Christopher A
CA
Henderson
Brian E
BE
Hoover
Robert N
RN
Kolonel
Laurence N
LN
Kraft
Peter
P
Ma
Jing
J
Le Marchand
Loïc
L
Overvad
Kim
K
Palli
Domenico
D
Stattin
Pär
P
Stampfer
Meir
M
Stram
Daniel O
DO
Thomas
Gilles
G
Thun
Michael J
MJ
Travis
Ruth C
RC
Trichopoulos
Dimitrios
D
Virtamo
Jarmo
J
Weinstein
Stephanie J
SJ
Yeager
Meredith
M
Kaaks
Rudolf
R
Hunter
David J
DJ
Hayes
Richard B
RB
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D040641:Quantitative Trait Loci; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D044465:White People / Q000235:genetics
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase