The relationship between low-penetrance genes, metabolic risk factors, and levels of endogenous 17ß-estradiol and progesterone, which play a role in breast cancer risk, remains unclear.
The aim of this study was to determine whether common polymorphisms in CYP17, in combination with metabolic risk factors (individually or clustered), alter salivary concentrations of free biologically active 17ß-estradiol and progesterone among healthy premenopausal Norwegian women.
Eight single nucleotide polymorphisms in CYP17 were genotyped in 203 healthy premenopausal women aged 25-35 yr in the Norwegian EBBA-I Study, conducted in 2000-2002. Daily salivary concentrations of 17ß-estradiol and progesterone were measured throughout one menstrual cycle. A clustered metabolic score was calculated, including waist circumference, mean arterial pressure, insulin resistance, fasting triglycerides, and total cholesterol/high-density lipoprotein cholesterol ratio. The study hypothesis was tested in multivariable linear regression and generalized estimating equation models.
Women in the upper tertile of clustered metabolic score with the CYP17 rs2486758 minor allele had daily salivary 17ß-estradiol concentrations that were 53% higher than other study women throughout the menstrual cycle (P