TY - JOUR
T1 - Familial correlations in postmenopausal serum concentrations of sex steroid hormones and other mitogens
T2 - A twins and sisters study
AU - Stone, Jennifer
AU - Folkerd, Elizabeth
AU - Doody, Deborah
AU - Schroen, Chris
AU - Treloar, Susan A.
AU - Giles, Graham G.
AU - Pike, Malcolm C.
AU - English, Dallas R.
AU - Southey, Melissa C.
AU - Hopper, John L.
AU - Dowsett, Mitch
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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 (E2), 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 (h2) and nongenetic factors common to sisterships (c2) 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 E2 (P = 0.3), and the respective h2 estimates were 0.56 (SE = 0.14), 0.53 (0.17), 0.39 (0.14), and 0.14 (0.16). For log E2 and square-root T, c2 estimates were 0.39 (0.14) and 0.22 (0.12). Conclusion: There are strong familial correlations in postmenopausal SHBG, IGF-I, and to a lesser extent T, which are consistent with a genetic etiology. For E2, and to a lesser extent T, correlations are consistent with substantial nongenetic familial factors. The latter might include maternal effects.
AB - 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 (E2), 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 (h2) and nongenetic factors common to sisterships (c2) 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 E2 (P = 0.3), and the respective h2 estimates were 0.56 (SE = 0.14), 0.53 (0.17), 0.39 (0.14), and 0.14 (0.16). For log E2 and square-root T, c2 estimates were 0.39 (0.14) and 0.22 (0.12). Conclusion: There are strong familial correlations in postmenopausal SHBG, IGF-I, and to a lesser extent T, which are consistent with a genetic etiology. For E2, and to a lesser extent T, correlations are consistent with substantial nongenetic familial factors. The latter might include maternal effects.
UR - https://www.scopus.com/pages/publications/73249119587
U2 - 10.1210/jc.2009-0713
DO - 10.1210/jc.2009-0713
M3 - Article
AN - SCOPUS:73249119587
SN - 0021-972X
VL - 94
SP - 4793
EP - 4800
JO - The Journal of Clinical Endocrinology & Metabolism
JF - The Journal of Clinical Endocrinology & Metabolism
IS - 12
ER -
