Associations among mammographic density, circulating sex hormones, and polymorphisms in sex hormone metabolism genes in postmenopausal women.
Mammographic density and serum sex hormone levels are important risk factors for breast cancer, but their associations with one another are unclear. We studied these phenotypes, together with single nucleotide polymorphisms (SNP) in genes related to sex hormone metabolism, in a cross-sectional study of 1,413 postmenopausal women from the European Prospective Investigation into Cancer and Nutrition-Norfolk. All women were >1 year postmenopausal and had not taken hormone replacement therapy for >3 months before sampling. Serum levels of 7 sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG), androstenedione, 17-OH-progesterone, estrone, and estrone sulfate] and 15 SNPs in the CYP17, CYP19, EDH17B2, SHBG, COMT, and CYP1B1 genes were studied. Mammograms nearest in time to the blood sampling were identified through the national breast screening program and visually assessed by three radiologists using the Boyd six-category and Wolfe four-category scales. We found a weak positive association between mammographic density and SHBG levels (P = 0.09) but no association with any other hormones. None of the SNPs, including those shown previously to be associated with estradiol or SHBG, showed significant associations with density. We conclude that mammographic density is largely independent of postmenopausal steroid hormone levels, indicating that these risk factors have, to a large extent, an independent etiology and suggesting that they may be independent predictors of breast cancer risk.
Warren
Ruth
R
Department of Radiology, University of Cambridge, United Kingdom. rmlw2@cam.ac.uk
Skinner
Jane
J
Sala
Evis
E
Denton
Erika
E
Dowsett
Mitch
M
Folkerd
Elizabeth
E
Healey
Catherine S
CS
Dunning
Alison
A
Doody
Deborah
D
Ponder
Bruce
B
Luben
Robert N
RN
Day
N E
NE
Easton
Douglas
D
D000368:Aged; D001141:Aromatase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase