Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women.
BACKGROUND
We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17beta-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women.


METHODS
The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI).


RESULTS
After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01).


CONCLUSIONS
SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density.
Crandall
Carolyn J
CJ
Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, UCLA Medicine/GIM, 911 Broxton Ave, 1st floor, Los Angeles, CA 90024, USA. ccrandall@mednet.ucla.edu
Sehl
Mary E
ME
Crawford
Sybil L
SL
Gold
Ellen B
EB
Habel
Laurel A
LA
Butler
Lesley M
LM
Sowers
Maryfran R
MR
Greendale
Gail A
GA
Sinsheimer
Janet S
JS
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000273:Adipose Tissue / Q000648:ultrastructure; D000328:Adult; D000367:Age Factors; D001141:Aromatase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases; D015992:Body Mass Index; D001940:Breast / Q000648:ultrastructure*; D001943:Breast Neoplasms / Q000453:epidemiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D005006:Ethnicity; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D042361:Mammary Glands, Human / Q000648:ultrastructure; D008327:Mammography; D008875:Middle Aged; D047648:Perimenopause; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1