Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women.
Experimental and clinical evidence suggests that 16alpha-hydroxylated estrogen metabolites, biologically strong estrogens, are associated with breast cancer risk, while 2-hydroxylated metabolites, with lower estrogenic activity, are weakly related to this disease. This study analyzes the association of breast cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone, in a prospective nested case-control study. Between 1987 and 1992, 10,786 women (ages 35-69 years) were recruited to a prospective study on breast cancer in Italy, the "Hormones and Diet in the Etiology of Breast Cancer" (ORDET) study. Women with a history of cancer and women on hormone therapy were excluded at baseline. At recruitment, overnight urine was collected from all participants and stored at -80 degrees C. After an average of 5.5 years of follow-up, 144 breast cancer cases and four matched controls for each case were identified among the participants of the cohort. Among premenopausal women, a higher ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone at baseline was associated with a reduced risk of breast cancer: women in the highest quintile of the ratio had an adjusted odds ratio (OR) for breast cancer of 0.58 [95% confidence interval (CI) = 0.25-1.34]. The corresponding adjusted OR in postmenopausal women was 1.29 (95% CI = 0.53-3.10). Results of this prospective study support the hypothesis that the estrogen metabolism pathway favoring 2-hydroxylation over 16alpha-hydroxylation is associated with a reduced risk of invasive breast cancer risk in premenopausal women.
Muti
P
P
Department of Social and Preventive Medicine, University at Buffalo, State University of New York at Buffalo, 14226, USA.
Bradlow
H L
HL
Micheli
A
A
Krogh
V
V
Freudenheim
J L
JL
Schünemann
H J
HJ
Stanulla
M
M
Yang
J
J
Sepkovic
D W
DW
Trevisan
M
M
Berrino
F
F
D000328:Adult; D000368:Aged; D001824:Body Constitution; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000209:etiology*; D016022:Case-Control Studies; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000378:metabolism*; D016015:Logistic Models; D008875:Middle Aged; D010298:Parity; D017698:Postmenopause / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism*; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D039181:Steroid 16-alpha-Hydroxylase
D004967:Estrogens; D006894:Hydroxyestrones; D039181:Steroid 16-alpha-Hydroxylase