Abstract
Background: Breast cancer rates in Asia are much lower than in Europe and North America. Within Asia, rates are lower in Mongolia than in neighboring countries. Variation in pregnancy exposure to endogenous hormone concentrations may explain the differences, but data are lacking. Methods: We measured maternal serum progesterone, prolactin, estradiol and estrone concentrations in the second half of pregnancy in urban and rural Mongolian, and U.S. women from Boston. Medical records provided information on maternal and perinatal factors. Geometric mean hormones were estimated from standard linear models with the log-hormone as the dependent variable and country as the independent variable adjusted for maternal and gestational age at blood draw. Results: Mean concentrations of prolactin (5722 vs. 4648 uIU/mL; p<0.0001) and estradiol (17.7 vs. 13.6 ng/mL; p<0.0001) were greater in Mongolian than U.S. women, while progesterone (147 vs. 201 ng/mL; p<00001) was lower. Mean hormone concentrations were similar in rural and urban Mongolian women. Results were generally similar with additional adjustment for gravidity, parity, height, body mass index at blood draw, education and alcohol use during pregnancy, and when stratified by offspring sex or parity. Conclusions: Mongolian women had greater concentrations of prolactin and estrogen and lower concentrations of progesterone than US women, while hormone concentrations were similar in rural and urban Mongolian pregnancies. Funding Statement: This research was supported by funding from the intramural program at the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. Declaration of Interests: None of the authors has a conflict of interest. Ethics Approval Statement: The study was approved by ethical review boards at Mongolia’s Ministry of Health, the National University of Mongolia, and in the United States (U.S.) at the National Cancer Institute (National Institutes of Health), and the Harvard School of Public Health and Brigham and Women’s Hospital in Boston. All participants provided written, informed consent.
Highlights
One of the strongest risk factors for breast cancer remains the woman’s country of birth
We investigated variations in pregnancy hormones that are associated with subsequent breast cancer risk in rural and urban Mongolian women, Asian populations with even lower breast cancer incidence than the Chinese, and compared them with
Our overall results for several hormones with established roles in breast carcinogenesis show differences between the maternal circulation in pregnancies occurring in Mongolia, with one of the lowest breast cancer incidence rates in the world, and in the US, with one of the highest incidence rates
Summary
One of the strongest risk factors for breast cancer remains the woman’s country of birth. Despite increases in breast cancer incidence in the developing world, rates in Northern and Western Europe and North America remain greater by approximately two to three times those of East and Southeast. Within Asia, rates in China and Japan are almost four to six times greater [1], respectively, than in neighboring Mongolia. These international differences appear largely due to environment, as incidence rates increase rapidly among Asian migrants to Western countries, reaching those of the host country by the second generation [2]. Differences in established breast cancer risk factors, including endogenous hormone concentrations, have long been speculated to explain these epidemiological observations [4,5], but evidence is lacking. Variation in pregnancy exposure to endogenous hormone concentrations may explain the differences, but data are lacking
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