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High mammographic density is an established breast cancer risk factor, and circulating oestrogen influences oestrogen-regulating gene expression in breast cancer development. However, less is known about the interrelationships of common variants in the  CYP19A1  gene, daily levels of oestrogens, mammographic density phenotypes and body mass index (BMI) in premenopausal women.    Methods  Based on plausible biological mechanisms related to the oestrogen pathway, we investigated the association of single nucleotide polymorphisms (SNPs) in  CYP19A1 , 17β-estradiol and mammographic density in 202 premenopausal women. DNA was genotyped using the Illumina Golden Gate platform. Daily salivary 17β-estradiol concentrations were measured throughout an entire menstrual cycle. Mammographic density phenotypes were assessed using a computer-assisted method (Madena). We determined associations using multivariable linear and logistic regression models.    Results  The minor alleles of  rs749292  were positively ( P  = 0.026), and the minor alleles of  rs7172156  were inversely ( P  = 0.002) associated with daily 17β-estradiol. We observed an 87% lower level of daily 17β-estradiol throughout a menstrual cycle in heavier women (BMI >23.6 kg/m 2 ) of  rs7172156  with minor genotype  aa  compared with major genotype  AA . Furthermore, the  rs749292  minor alleles were inversely associated with absolute mammographic density ( P  = 0.032). Lean women with  rs749292  minor alleles had 70 to 80% lower risk for high absolute mammographic density (>32.4 cm 2 );  Aa : odds ratio (OR) = 0.23 (95% CI 0.07 to 0.75). Lean women with  rs7172156  minor homozygous genotype had OR 5.45 for high absolute mammographic density ( aa : OR = 5.45 (95% CI 1.13 to 26.3)).    Conclusion  Our findings suggest that two SNPs in  CYP19A1 ,  rs749292  and  rs7172156 , are associated with both daily oestrogen levels and mammographic density phenotypes. BMI may modify these associations, but larger studies are needed.    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-014-0499-2) contains supplementary material, which is available to authorized users.

Gene variations in oestrogen pathways, CYP19A1, daily 17β-estradiol and mammographic density phenotypes in premenopausal women