Genetic polymorphism CYP17 rs2486758 and metabolic risk factors predict daily salivary 17β-estradiol concentration in healthy premenopausal Norwegian women. The EBBA-I study.
نویسندگان
چکیده
CONTEXT The relationship between low-penetrance genes, metabolic risk factors, and levels of endogenous 17β-estradiol and progesterone, which play a role in breast cancer risk, remains unclear. OBJECTIVE 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 17β-estradiol and progesterone among healthy premenopausal Norwegian women. DESIGN 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 17β-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. RESULTS Women in the upper tertile of clustered metabolic score with the CYP17 rs2486758 minor allele had daily salivary 17β-estradiol concentrations that were 53% higher than other study women throughout the menstrual cycle (P < 0.001). Similarly, women in the upper tertile of total cholesterol/high-density lipoprotein cholesterol ratio, fasting triglycerides, and insulin resistance had 44, 32, and 24% higher daily salivary 17β-estradiol concentrations, respectively (all P < 0.05). CONCLUSION The CYP17 rs2486758 minor allele may predispose to higher 17β-estradiol levels, particularly in premenopausal women with a high clustered metabolic score. Thus, modification of metabolic risk factors may have significant implications for the prevention of breast cancer in women with the minor allele of CYP17 rs2486758.
منابع مشابه
Ovarian hormones and reproductive risk factors for breast cancer in premenopausal women: the Norwegian EBBA-I study
BACKGROUND Ovarian hormones, parity and length of 'menarche-to-first birth' time interval are known risk factors for breast cancer, yet the associations between 17β-estradiol, progesterone and these reproductive factors remain unclear. METHODS A total of 204 women (25-35 years) who participated in the Norwegian EBBA-I study collected daily saliva samples for one complete menstrual cycle, and ...
متن کاملCyclic endogenous estrogen and progesterone vary by mammographic density phenotypes in premenopausal women
Estrogen and progesterone are key factors in the development of breast cancer, but it remains unclear whether these hormones are associated with mammographic density phenotypes in premenopausal women. We measured percent mammographic density, nondense area, and absolute mammographic density using computer-assisted breast density readings (Madena) from digitized mammograms taken on a scheduled d...
متن کاملPhysical activity, heart rate, metabolic profile, and estradiol in premenopausal women.
PURPOSE To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical activity (LPA), resting heart rate (HR), blood pressure (BP), anthropometry, and serum glucose, lipids,...
متن کاملHigh-density lipoprotein-cholesterol, daily estradiol and progesterone, and mammographic density phenotypes in premenopausal women.
High-density lipoprotein-cholesterol (HDL-C) may influence the proliferation of breast tumor cells, but it is unclear whether low HDL-C levels, alone or in combination with cyclic estrogen and progesterone, are associated with mammographic density, a strong predictor of breast cancer development. Fasting morning serum concentrations of HDL-C were assessed in 202 premenopausal women, 25 to 35 ye...
متن کاملMetabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study.
Low serum high-density lipoprotein cholesterol (HDL-C) is an important component of the metabolic syndrome and has recently been related to increased breast cancer risk in overweight and obese women. We therefore questioned whether serum HDL-C might be a biologically sound marker of breast cancer risk. We obtained cross-sectional data among 206 healthy women ages 25 to 35 years who participated...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of clinical endocrinology and metabolism
دوره 97 5 شماره
صفحات -
تاریخ انتشار 2012