Genetic determinants of mammographic density.
BACKGROUND
Changes in breast density are highly correlated with steroid hormone exposure.


METHODS
In a cross-sectional study of 396 Caucasian and African-American women, we evaluated whether polymorphisms in genes involved in steroid hormone biosynthesis and metabolism, CYP17 (T27C), COMT (Val158Met), 17HSDB1 (Ser312Gly) and 3HSDB1 (Asn367Thr), predict mammographic density. We also evaluated whether associations vary by menopausal and hormone replacement therapy status.


RESULTS
We found no strong consistent relationships between polymorphisms in these genes and breast density. African-American women homozygous for the Thr allele of 3HSDB1 had increased density (the absolute difference versus the Asn/Asn genotype was +19.7%; P trend = 0.02), while Caucasian homozygous women had decreased density (-5.1%; P trend = 0.04). Among premenopausal women, carriers of the Ser allele had (not significantly) greater density (versus Gly/Gly genotype: +7.1%; P trend = 0.07). In addition, among current users of hormone replacement therapy, we observed that women with the low-activity Met/Met genotype of COMT had greater breast density (versus the Val/Val genotype: +11.7%; P trend = 0.01).


CONCLUSIONS
Additional large studies evaluating these and other candidate breast cancer genes will be required to determine what proportion, if any, of the interindividual differences in breast density are due to underlying genetic variation in genes involved in steroid hormone biosynthesis or metabolism.
Haiman
Christopher A
CA
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA. haiman@usc.edu
Bernstein
Leslie
L
Berg
David
D
Ingles
Sue A
SA
Salane
Martine
M
Ursin
Giske
G
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D044383:Black People / Q000235:genetics*; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D006728:Hormones / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008327:Mammography; D008780:Methyltransferases / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D044465:White People / Q000235:genetics*; D001741:Black or African American
D006728:Hormones; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D008780:Methyltransferases; D002394:Catechol O-Methyltransferase