PMID- 15199113
OWN - NLM
STAT- MEDLINE
DCOM- 20040624
LR  - 20220408
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Linking)
VI  - 96
IP  - 12
DP  - 2004 Jun 16
TI  - Polymorphisms associated with circulating sex hormone levels in postmenopausal 
      women.
PG  - 936-45
AB  - BACKGROUND: Reports suggest a relationship between circulating sex hormone levels 
      and breast cancer risk, but genetic association studies have been inconclusive. 
      We investigated the association between levels of sex hormones and single 
      nucleotide polymorphisms (SNPs) in genes coding for the enzymes that regulate 
      them. METHODS: We assayed circulating levels of estradiol, testosterone, estrone, 
      androstenedione, 17alpha-hydroxyprogesterone, and sex hormone-binding globulin 
      (SHBG) in 1975 normal postmenopausal women. Fifteen SNPs in the CYP17, CYP19, 
      EDH17B2, SHBG, COMT, and CYP1B1 genes were genotyped in these postmenopausal 
      women and in a breast cancer case-control study. Associations of genotypes with 
      breast cancer risk were evaluated in the case-control study and with hormone 
      levels in the postmenopausal women using multiple linear regression with assay 
      batch, body mass index, parity, peri- or postmenopausal status, and age band as 
      covariates. RESULTS: CYP19 SNPs (rs10046 and [TCT]+/-) were associated with 
      differences in estradiol level (P =.0006 and P =.0003, respectively) and the 
      estradiol : testosterone ratio (P =.000001() and P =.002). SNP rs10046 explained 
      1.6% of the variance (r2) in the estradiol : testosterone ratio. SHBG SNPs (5' 
      untranslated region [5'UTR] g-a and D356N) were associated with both SHBG levels 
      (P<10(-6) and P =.005) and the estradiol : SHBG ratio (P =().000008() and P 
      =.01). These SNPs explained 2.4% and 0.6% of the variance in SHBG levels, 
      respectively. SNPs in the other genes were not associated with differences in any 
      hormone levels, and none were statistically significantly associated with breast 
      cancer risk. CONCLUSION: Genetic variation in CYP19 and SHBG contributes to 
      variance in circulating hormone levels between postmenopausal women, but low r2 
      values may explain why these genes have given inconclusive results in breast 
      cancer case-control studies.
FAU - Dunning, Alison M
AU  - Dunning AM
AD  - Cancer Research UK, Department of Oncology, University of Cambridge, Strangeways 
      Research Laboratory, Cambridge, UK. alisond@srl.cam.ac.uk
FAU - Dowsett, Mitch
AU  - Dowsett M
FAU - Healey, Catherine S
AU  - Healey CS
FAU - Tee, Louise
AU  - Tee L
FAU - Luben, Robert N
AU  - Luben RN
FAU - Folkerd, Elizabeth
AU  - Folkerd E
FAU - Novik, Karen L
AU  - Novik KL
FAU - Kelemen, Livia
AU  - Kelemen L
FAU - Ogata, Saeko
AU  - Ogata S
FAU - Pharoah, Paul D P
AU  - Pharoah PD
FAU - Easton, Douglas F
AU  - Easton DF
FAU - Day, N E
AU  - Day NE
FAU - Ponder, Bruce A J
AU  - Ponder BA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Sex Hormone-Binding Globulin)
RN  - 2DI9HA706A (Estrone)
RN  - 3XMK78S47O (Testosterone)
RN  - 409J2J96VR (Androstenedione)
RN  - 4TI98Z838E (Estradiol)
RN  - 68-96-2 (17-alpha-Hydroxyprogesterone)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP1B1 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
CIN - J Natl Cancer Inst. 2005 Jan 19;97(2):152-3; author reply 153-4. PMID: 15657347
MH  - 17-alpha-Hydroxyprogesterone/blood
MH  - Aged
MH  - Androstenedione/blood
MH  - Aromatase/*genetics
MH  - Aryl Hydrocarbon Hydroxylases/genetics
MH  - Breast Neoplasms/blood/*enzymology/*genetics
MH  - Case-Control Studies
MH  - Catechol O-Methyltransferase/genetics
MH  - Cytochrome P-450 CYP1B1
MH  - England
MH  - Estradiol/blood
MH  - Estrone/blood
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Genotype
MH  - Gonadal Steroid Hormones/*blood/metabolism
MH  - Humans
MH  - Linear Models
MH  - Middle Aged
MH  - Odds Ratio
MH  - *Polymorphism, Single Nucleotide
MH  - *Postmenopause/blood/genetics
MH  - Sex Hormone-Binding Globulin/*genetics/metabolism
MH  - Steroid 17-alpha-Hydroxylase/genetics
MH  - Testosterone/blood
EDAT- 2004/06/17 05:00
MHDA- 2004/06/25 05:00
CRDT- 2004/06/17 05:00
PHST- 2004/06/17 05:00 [pubmed]
PHST- 2004/06/25 05:00 [medline]
PHST- 2004/06/17 05:00 [entrez]
AID - 10.1093/jnci/djh167 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2004 Jun 16;96(12):936-45. doi: 10.1093/jnci/djh167.