Familial correlations in postmenopausal serum concentrations of sex steroid hormones and other mitogens: a twins and sisters study.
BACKGROUND
Serum concentrations of some hormones are risk factors for certain cancers, but little is known about their familial associations especially for females.


METHODS
We measured serum concentrations of estradiol (E(2)), testosterone (T), SHBG, prolactin, and IGF-I for 645 Australian female postmenopausal twins and their sisters [182 monozygotic (MZ) and 107 dizygotic (DZ) pairs and 67 nontwin sisters] using well-established immunoassays. After suitable transformation and adjusting for age, body mass index (BMI), and time since menopause, familial correlations and proportions of variance attributed to genetic (h(2)) and nongenetic factors common to sisterships (c(2)) were estimated under the classic twin multivariate normal model using FISHER.


RESULTS
For all serum concentrations except prolactin, MZ, DZ, and sister pairs were correlated (P < 0.001). MZ correlations were in the range 0.5-0.7, and for all serum concentrations, there were no differences between DZ and sister correlations. MZ correlations were greater than DZ and sister correlations for log SHBG (P = 0.0001), IGF-I (P = 0.0002), and square-root T (P = 0.007) but not log E(2) (P = 0.3), and the respective h(2) estimates were 0.56 (SE = 0.14), 0.53 (0.17), 0.39 (0.14), and 0.14 (0.16). For log E(2) and square-root T, c(2) estimates were 0.39 (0.14) and 0.22 (0.12).


CONCLUSIONS
There are strong familial correlations in postmenopausal SHBG, IGF-I, and to a lesser extent T, which are consistent with a genetic etiology. For E(2), and to a lesser extent T, correlations are consistent with substantial nongenetic familial factors. The latter might include maternal effects.
Stone
Jennifer
J
Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, University of Melbourne, Level 1, 723 Swanston Street, Carlton, Victoria 3053 Australia.
Folkerd
Elizabeth
E
Doody
Deborah
D
Schroen
Chris
C
Treloar
Susan A
SA
Giles
Graham G
GG
Pike
Malcolm C
MC
English
Dallas R
DR
Southey
Melissa C
MC
Hopper
John L
JL
Dowsett
Mitch
M
D000328:Adult; D000368:Aged; D001315:Australia; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D008934:Mitogens / Q000097:blood*; D017698:Postmenopause / Q000097:blood* / Q000235:genetics*; D011388:Prolactin / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D012739:Gonadal Steroid Hormones; D008934:Mitogens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011388:Prolactin