Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women.
Women with high circulating estrogen concentrations have an increased risk of breast cancer; thus, it is important to understand factors, including genetic variability, that influence estrogen concentrations. Several genetic polymorphisms that may influence sex hormone concentrations have been identified, including CYP17 (5'-untranslated region T-->C), CYP19 [intron 4 (TTTA)(n = 7-13) and a 3-bp deletion (-3)], CYP1B1 (Val(432)Leu), and COMT (Val(108/158)Met). We examined associations between these polymorphisms and serum concentrations of estrogens, androgens, and sex hormone-binding globulin and urinary concentrations of 2- and 16alpha-hydroxyestrone in 171 postmenopausal women, using data from the prerandomization visit of an exercise clinical trial. Participants were sedentary, not taking hormone therapy, and had a body mass index >24.0. Compared with noncarriers, women carrying two CYP19 7r(-3) alleles had 26% lower estrone (P < 0.001), 19% lower estradiol (P = 0.01), 23% lower free estradiol (P = 0.01), and 22% higher sex hormone-binding globulin concentrations (P = 0.06). Compared with noncarriers, women carrying at least one CYP19 8r allele had 20% higher estrone (P = 0.003), 18% higher estradiol (P = 0.02), and 21% higher free estradiol concentrations (P = 0.01). Women with the COMT Met/Met genotype had 28% higher 2-hydroxyestrone (P = 0.08) and 31% higher 16alpha-hydroxyestrone concentrations (P = 0.02), compared with Val/Val women. Few associations were found for CYP17 and CYP1B1 or with serum androgen concentrations. This study provides further evidence that genetic variation may appreciably alter sex hormone concentrations in postmenopausal women not taking hormone therapy.
Tworoger
Shelley S
SS
The Fred Hutchinson Cancer Research Center, Cancer Prevention Research Program, Seattle, Washington, USA.
Chubak
Jessica
J
Aiello
Erin J
EJ
Ulrich
Cornelia M
CM
Atkinson
Charlotte
C
Potter
John D
JD
Yasui
Yutaka
Y
Stapleton
Patricia L
PL
Lampe
Johanna W
JW
Farin
Federico M
FM
Stanczyk
Frank Z
FZ
McTiernan
Anne
A
D000368:Aged; D000483:Alleles; D001141:Aromatase / Q000097:blood / Q000235:genetics* / Q000502:physiology; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics* / Q000502:physiology; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D016001:Confidence Intervals; D065633:Cytochrome P-450 CYP1B1; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000652:urine*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood* / Q000652:urine; D012306:Risk; D013254:Steroid 17-alpha-Hydroxylase / Q000097:blood / Q000235:genetics* / Q000502:physiology
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase