Citations 2
Establishment of harmonized international reference ranges for plasma estradiol concentrations in postmenopausal women
Cui, Jinghan, Hankinson, Susan E. , Santen, Richard J. , Boutot, Maegan E., Budd, Jeffrey R. , Dowsett, Mitch, Goetz, Matthew P, Guranich, Catherine, Houghton, Serena, Ingle, J , Jones, Micheal E., Rinaldi, Sabina , Rosner, Bernard, Vesper, Hubert W. , Eliassen, A Heather, Swerdlow, Anthony J, Vachon, Celine M. , Richardson, Harriet , Qian, Jing , Jones, Michael E. , Rinaldi, Sabina , Singh, Ravinder J , Vachon, Celine M. , Qian, Jing , Hankinson, Susan E. , Jones, Michael E , Matsumoto, Alvin M. , Dowsett, Mitch , Houghton, Serena C. , Ingle, James N. , Rosner, Bernard A., Schoemaker, Minouk J. , Milne, Roger L. , Swerdlow, Anthony J
The Journal of Clinical Endocrinology & Metabolism | May 9, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Context Prior reports of plasma estradiol concentrations and their reference ranges in postmenopausal women identified marked variation, in part due to assay method and body mass index (BMI). Objective To develop an international reference range for plasma estradiol in postmenopausal women, support accurate assessment of concentrations during systemic and local (eg, vaginal) estradiol therapy, and improve risk prediction for diseases, including osteoporosis, breast, and endometrial cancers. Methodology Estradiol concentrations were measured using primarily liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays in 5 international cohorts of community-dwelling, postmenopausal women of primarily European ancestry aged 38-100 years who were not using exogenous estrogens (n = 7206). Measurements were harmonized to the Centers for Disease Control and Prevention (CDC) reference measurement procedure (RMP) by re-assaying a subset of samples for each cohort and generating recalibration equations. Reference intervals were determined for all women, non-obese women, and specific BMI categories. Results Estradiol concentrations from separate LC-MS/MS assays correlated closely with the CDC RMP, and harmonization minimized inter-assay variability. Estradiol concentrations correlated with BMI but not with chronological age. The reference range (2.5th-97.5th percentile) was 1.1-18.2 pg/mL (4.0-66.8 pmol/L) with median of 4.9 pg/mL (18.0 pmol/L) for all postmenopausal women and 1.1-12.5 pg/mL (4.0-45.9 pmol/L) with median of 4.1 pg/mL (15.1 pmol/L) for non-obese women (BMI < 30). Reference ranges increased progressively with higher BMI categories. Conclusion Cross-calibration of estradiol measurements with the CDC RP enabled the development of harmonized plasma estradiol reference ranges for postmenopausal women who were not using exogenous estrogens, suitable for future studies to establish clinical utility. Increasing obesity in postmenopausal women was associated with increasing estradiol concentration and BMI category-specific reference ranges.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
Park, JooYong , Choi, Ji‐Yeob , Chung, Seokang , Song, Nan , Park, Sue K. , Han, Wonshik , Noh, Dong‐Young , Ahn, Sei-Hyun, Lee, Jong Won, Kim, Mi Kyung , Jee, Sun Ha , Wen, Wanqing , Bolla, Manjeet K. , Wang, Qin , Michailidou, Kyriaki , Shah, Mitul , Conroy, Don, Harrington, Patricia, Mayes, Rebecca , Hall, Per , Patel, Alpa V. , Couch, Fergus J. , Sawyer, Elinor J. , Roylance, Rebecca , Bojesen, Stig E. , Flyger, Henrik, Lambrechts, Diether , Baten, Adinda , Matsuo, Keitaro , Ito, Hidemi , Guénel, Pascal , Keeman, Renske , Schmidt, Marjanka K. , Wu, Anna H. , Tseng, Chiu-Chen, Cox, Angela , Investigators, kConFab, Andrulis, Irene L. , Hopper, John L., Wu, Pei‐Ei , Shen, Chen‐Yang , Fasching, Peter A. , Ekici, Arif B. , Muir, Kenneth, Brenner, Hermann , Arndt, Volker , Jones, Michael E. , Swerdlow, Anthony J, Hoppe, Reiner , Ko, Yon-Dschun, Hartman, Mikael , Li, Jingmei , Mannermaa, Arto, Hartikainen, Jaana M. , Benítez, Javier, Haiman, Christopher A. , Dörk, Thilo , Bogdanova, Natalia , Teo, Soo‐Hwang , Taib, Nur Aishah Mohd , Fletcher, Olivia, Johnson, Nichola , Grip, Mervi, Winqvist, Robert , Nevanlinna, Heli , Lindblom, Annika , Wendt, Camilla, Kristensen, Vessela N. , Collaborators, NBCS, Tollenaar, Rob A.�E.�M. , Heemskerk‐Gerritsen, Bernadette A. M. , Bonanni, Bernardo , Hamann, Ute, Manoochehri, Mehdi, Martinez, Maria Elena, Easton, Douglas F., Yoo, Keun-Young, Lambrechts, Diether , Song, Nan , Park, Sue K , Kim, Mi Kyung , Dennis, Joe , Michailidou, Kyriaki , Hall, Per N , Matsuo, Keitaro , Ito, Hidemi , Keeman, Renske , Schmidt, Marjanka K , Fasching, Peter A , Brenner, Hermann , Arndt, Volker , Hartikainen, Jaana M , Dörk, Thilo , Bogdanova, Natalia V , Johnson, Nichola , Nevanlinna, H , Heemskerk-Gerritsen, Bernadette A M , Bonanni, Bernardo , Lambrechts, Diether , Teo, Soo H , Jones, Michael E , Lambrechts, Diether , Cox, Angela , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , Ekici, Arif B , Bojesen, Stig E , Lindblom, Annika , Mohd Taib, Nur Aishah , Sawyer, Elinor J , Choi, Jaesung , Czene, Kamila , Teras, Lauren R. , Couch, Fergus J. , Olson, Janet E. , Truong, Thérèse , Cross, Simon S. , Investigators, kConFab, Southey, Melissa C. , Lophatananon, Artitaya , Ko, Yon‐Dschun, Mannermaa, Arto , González‐Neira, Anna , Fletcher, Olivia , Blomqvist, Carl , Wendt, Camilla, Collaborators, NBCS, Radice, Paolo , Manoochehri, Mehdi, Lacey, James V. , Dunning, Alison M. , Pharoah, Paul D.P. , Kang, Daehee
Cancers | May 14, 2021 | Volume: 13 | Issue: 10 | Pages: 2370
In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.