Publications by authors named "Rebecca Troisi"

97 Publications

Exposure to endocrine-disrupting chemicals in utero and thyroid cancer risk in offspring - Authors' reply.

Lancet Diabetes Endocrinol 2021 05 23;9(5):255-256. Epub 2021 Mar 23.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA.

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http://dx.doi.org/10.1016/S2213-8587(21)00073-5DOI Listing
May 2021

Maternal autoimmune disease is not associated with cancer in the offspring.

Acta Paediatr 2021 Feb 27. Epub 2021 Feb 27.

Pediatrics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Aim: Autoimmune disease and its medication are associated with increased cancer risk in adults, but it is unknown whether maternal autoimmune disease and/or medication use in pregnancy are associated with increased cancer risk in offspring.

Methods: In this case-control study, we identified all patients under 20 years of age with their first cancer diagnosis in 1996-2014 from the Finnish Cancer Registry (n = 2029) and 1:5 population-based controls (n = 10,103) from the Medical Birth Register. We obtained information on maternal autoimmune disease and its medication from the relevant Finnish registries and used conditional logistic regression to analyse the risk of offspring cancer after maternal autoimmune disease exposure.

Results: The odds ratio (OR) for cancer in offspring following maternal autoimmune exposure was 0.76 (95% confidence interval [CI] 0.47-1.23). Individual ORs for inflammatory bowel and connective tissue diseases were 1.08 (95% CI 0.56-2.01) and 0.50 (95% CI 0.23-1.08), respectively. The OR for maternal autoimmune medication was 0.95 (95% CI 0.80-1.14) overall and similar by drug subtype. There was an increased risk with medication in late pregnancy but the ORs were unstable owing to small numbers.

Conclusion: Our study does not support an increased cancer risk among offspring of women with autoimmune disease or its medication during pregnancy.
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http://dx.doi.org/10.1111/apa.15821DOI Listing
February 2021

Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring: a Nordic population-based nested case-control study.

Lancet Diabetes Endocrinol 2021 02 18;9(2):94-105. Epub 2020 Dec 18.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cancer Registry of Norway, Oslo, Norway.

Background: Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified.

Methods: In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs.

Results: Of the 2437 cases, 1967 (81·4%) had papillary carcinomas, 1880 (77·1%) were women, and 1384 (56·7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1·14 [95% CI 1·05-1·23]) and congenital hypothyroidism (4·55 [1·58-13·08]); maternal diabetes before pregnancy (OR 1·69 [0·98-2·93]) and postpartum haemorrhage (OR 1·28 [1·06-1·55]); and (from registry data in Denmark) maternal hypothyroidism (18·12 [10·52-31·20]), hyperthyroidism (11·91 [6·77-20·94]), goiter (67·36 [39·89-113·76]), and benign thyroid neoplasms (22·50 [6·93-73·06]) were each associated with an increased risk of thyroid cancer in offspring.

Interpretation: In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring.

Funding: Intramural Research Program of the National Cancer Institute (National Institutes of Health).
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http://dx.doi.org/10.1016/S2213-8587(20)30399-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875310PMC
February 2021

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults.

BMJ 2020 12 2;371:m4060. Epub 2020 Dec 2.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

Objective: To examine associations between birth defects and cancer from birth into adulthood.

Design: Population based nested case-control study.

Setting: Nationwide health registries in Denmark, Finland, Norway, and Sweden.

Participants: 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.

Main Outcome Measures: Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.

Results: Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.

Conclusions: The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.
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http://dx.doi.org/10.1136/bmj.m4060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708828PMC
December 2020

Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies.

J Dev Orig Health Dis 2020 Oct 28:1-8. Epub 2020 Oct 28.

Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6-51 and HR = 7.0, 95% CI 1.5-33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88-1.5) or diabetes (HR = 1.1, 95% CI 0.9-1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84-20) or general population (SIR: 1.9, 95% CI 1.0-3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.
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http://dx.doi.org/10.1017/S2040174420000872DOI Listing
October 2020

"I'm not a freshi": Culture shock, puberty and growing up as British-Bangladeshi girls.

Soc Sci Med 2020 08 21;258:113058. Epub 2020 May 21.

Department of Anthropology, Durham University, South Road, Durham, DH1 3LE, United Kingdom. Electronic address:

Early puberty is a risk factor for adult diseases and biomedical and psychosocial research implicate growth (in height and weight) and stress as modifiable drivers of early puberty. Seldom have studies examined these drivers simultaneously or concurrently using quantitative and qualitative methods. Within the context of migration, we used mixed-methods to compare growth, stress and puberty in a study of 488 girls, aged 5-16, who were either Bangladeshi, first-generation migrant to the UK, second-generation migrant, or white British (conducted between 2009 and 2011). Using a biocultural framework, we asked the questions: 1) Does migration accelerate pubertal processes? 2) What biocultural markers are associated with migration? 3) What biocultural markers are associated with puberty? Girls self-reported pubertal stage, recalled 24-h dietary intake, and answered questions relating to dress, food, and ethnic identity. We collected anthropometrics and assayed saliva specimens for dehydroepiandrosterone-sulfate (DHEA-S) to assess adrenarcheal status. Our findings demonstrate that first-generation migrants had earlier puberty than second-generation migrants and Bangladeshi girls. British style of dress did not increase with migration, while dietary choices did, which were reflected in increasing body mass index. However, the widely-used phrase, "I'm proud of my religion, but not my culture" demonstrated that ethnic identity was aligned more with Islamic religion than 'Bangladeshi culture.' This was epitomized by wearing the hijab, but denial of eating rice. The social correlates of puberty, such as 'practicing' wearing the hijab and becoming 'dedicated to the scarf,' occurred at the same ages as adrenarche and menarche, respectively, among first-generation girls. We suggest that the rejection of 'Bangladeshi culture' might be a source of psychosocial stress for first-generation girls, and this may explain elevated DHEA-S levels and early puberty compared to their second-generation counterparts. Our results support a biocultural model of adolescence, a period for biological embedding of culture, when biological and psychosocial factors adjust developmental timing with potential positive and negative implications for long-term health.
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http://dx.doi.org/10.1016/j.socscimed.2020.113058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369632PMC
August 2020

Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women: a registry-based study.

Br J Cancer 2020 07 27;123(1):161-166. Epub 2020 Apr 27.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Background: Non-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear.

Methods: Using data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970-2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases' birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs.

Results: The risk of SCSTs, but not GCTs, decreased with higher age at last birth [≥40 versus <25 years: OR 0.48 (95% CI 0.23-0.98)]. The risk of SCSTs (but not GCTs) also decreased with shorter time since last birth. Number of births, preterm birth, preeclampsia, and offspring size were not associated with risk of SCSTs or GCTs.

Conclusions: We found a decreased risk of SCSTs with higher age at last birth and shorter time since last birth. The risk of SCSTs (but not GCTs) may be influenced by the woman's reproductive history.
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http://dx.doi.org/10.1038/s41416-020-0849-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340776PMC
July 2020

Birthweight and all-cause mortality after childhood and adolescent leukemia: a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State.

Acta Oncol 2020 Aug 14;59(8):949-958. Epub 2020 Mar 14.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia. In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia. Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (≥4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged ≤1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8). This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.
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http://dx.doi.org/10.1080/0284186X.2020.1738546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392817PMC
August 2020

Assessing Endogenous and Exogenous Hormone Exposures and Breast Development in a Migrant Study of Bangladeshi and British Girls.

Int J Environ Res Public Health 2020 02 13;17(4). Epub 2020 Feb 13.

Department of Epidemiology, Mailman School of Public Health, New York, NY 10032, USA.

Timing of breast development (or thelarche) and its endogenous and exogenous determinants may underlie global variation in breast cancer incidence. The study objectives were to characterize endogenous estrogen levels and bisphenol A (BPA) exposure using a migrant study of adolescent girls and test whether concentrations explained differences in thelarche by birthplace and growth environment. Estrogen metabolites (EM) and BPA-glucuronide (BPA-G) were quantified in urine spot samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) from a cross-sectional study of Bangladeshi, first- and second-generation Bangladeshi migrants to the UK, and white British girls aged 5-16 years ( = 348). Thelarche status at the time of interview was self-reported and defined equivalent to Tanner Stage ≥2. We compared geometric means (and 95% confidence interval (CIs)) of EM and BPA-G using linear regression and assessed whether EM and BPA-G explained any of the association between exposure to the UK and the age at thelarche using hazard ratios and 95% confidence intervals. Average EM decreased with exposure to the UK, whereas BPA-G increased and was significantly higher among white British (0.007 ng/mL, 95% CI: 0.0024-0.0217) and second-generation British-Bangladeshi girls (0.009 ng/mL, 95% CI: 0.0040-0.0187) compared to Bangladeshi girls (0.002 ng/mL, 95% CI: 0.0018-0.0034). Two of four EM ratios (16-pathway/parent and parent/all pathways) were significantly associated with thelarche. The relationship between exposure to the UK and thelarche did not change appreciably after adding EM and BPA-G to the models. While BPA-G is often considered a ubiquitous exposure, our findings suggest it can vary based on birthplace and growth environment, with increasing levels for girls who were born in or moved to the UK. Our study did not provide statistically significant evidence that BPA-G or EM concentrations explained earlier thelarche among girls who were born or raised in the UK.
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http://dx.doi.org/10.3390/ijerph17041185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068451PMC
February 2020

Maternal Pregnancy Hormone Concentrations in Countries with Very Low and High Breast Cancer Risk.

Int J Environ Res Public Health 2020 01 28;17(3). Epub 2020 Jan 28.

Epidemiology and Biostatistics Program, Division of Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.

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 a cross-sectional study of urban ( = 143-194 depending on the analyte) and rural ( = 150-193) Mongolian women, and U.S. women from Boston ( = 66-204). 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; < 0.0001) and estradiol (17.7 vs. 13.6 ng/mL; < 0.0001) were greater in Mongolian than U.S. women, while progesterone (147 vs. 201 ng/mL; < 0.0001) 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 U.S. women, while hormone concentrations were similar in rural and urban Mongolian pregnancies.

Impact: These data do not support the hypothesis that estrogen concentrations in pregnant women are lower in Mongolian compared with Caucasian women.
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http://dx.doi.org/10.3390/ijerph17030823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037832PMC
January 2020

Gender Identity and Sexual Orientation Identity in Women and Men Prenatally Exposed to Diethylstilbestrol.

Arch Sex Behav 2020 02 23;49(2):447-454. Epub 2020 Jan 23.

Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.

We assessed the associations of prenatal diethylstilbestrol (DES) exposure, a potent estrogen, with sexual orientation and gender identity in 3306 women and 1848 men who participated in a study of prenatal DES exposure. Odds ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression models adjusted for birth year, study cohort, and education. Among women, the OR for DES in relation to reporting sexual orientation identity as nonheterosexual was 0.61 (95% CI 0.40-0.92) primarily due to a strong inverse association with a lesbian identity (OR 0.44, 95% CI 0.25-0.76). Among men, the OR for DES in relation to reporting a nonheterosexual sexual orientation identity was 1.4 (95% CI 0.82-2.4), and ORs were similar for having a gay identity (1.4, 95% CI 0.72-2.85) and bisexual identity (1.4, 95% CI 0.57-3.5). Only five individuals reported a gender identity not conforming to that assigned at birth, preventing meaningful analysis. Women who were prenatally exposed to DES were less likely to have a lesbian or bisexual orientation, while DES-exposed men were somewhat more likely to report being gay or bisexual, but estimates were imprecise.
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http://dx.doi.org/10.1007/s10508-020-01637-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031187PMC
February 2020

Pubertal timing and breast density in young women: a prospective cohort study.

Breast Cancer Res 2019 11 14;21(1):122. Epub 2019 Nov 14.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk.

Methods: From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.

Results: The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)).

Conclusions: Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.
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http://dx.doi.org/10.1186/s13058-019-1209-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857297PMC
November 2019

Comparison of seasonal serum 25-hydroxyvitamin D concentrations among pregnant women in Mongolia and Boston.

J Steroid Biochem Mol Biol 2019 10 16;193:105427. Epub 2019 Jul 16.

Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, SPH-2 Floor 3, Boston, MA, 02115, USA; Mongolian Health Initiative Non-Governmental Organization, Bayanzurkh District, Ulaanbaatar, Mongolia; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA. Electronic address:

Adequate vitamin D status during pregnancy is important for developing fetal bone strength and density and may play a role in preventing a range of skeletal and non-skeletal diseases in both mothers and children. We previously identified Mongolian women of reproductive age to have the lowest vitamin D levels yet observed in any population globally, which renders this population uniquely important in vitamin D research. In this study, we measured the seasonal distribution of 25-hydroxyvitamin D (25(OH)D) concentration in 390 healthy third trimester pregnant women living in urban and rural Mongolia using DiaSorin LIAISON and compared this distribution to that of 206 third trimester women living in Boston, USA. Also, we analyzed seasonally-independent associations between (25(OH)D) levels and selected predictors in both groups using quantile regression. Mean 25(OH)D levels were significantly higher and less seasonal in Boston (seasonal range: 27.1 ± 7.0-31.5 ± 7.7 ng/ml) than in Mongolia (seasonal range: 11.2 ± 3.9-19.2 ± 6.7 ng/ml). Adjusting for month of blood draw, higher 25(OH)D levels were significantly associated with older age, lower gravidity, lower BMI, and lack of a college or university degree among Boston participants, however, only gravidity was robust to multivariable adjustment. No assessed characteristics were independently predictive in Mongolia, likely due to universally low 25(OH)D levels and a resulting lack of between-person variation. In conclusion, vitamin D status among pregnant Mongolians is severely depressed throughout the year and should be addressed through fortification and supplementation, while in the U.S., deficiency is associated with specific characteristics targetable through supplementation.
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http://dx.doi.org/10.1016/j.jsbmb.2019.105427DOI Listing
October 2019

Prenatal Diethylstilbestrol Exposure and Risk of Depression in Women and Men.

Epidemiology 2019 09;30(5):679-686

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Background: Prenatal exposure to diethylstilbestrol (DES), an endocrine-disrupting chemical, may be associated with depression in adulthood, but previous findings are inconsistent.

Methods: Women (3,888 DES exposed and 1,729 unexposed) and men (1,021 DES exposed and 1,042 unexposed) participating in the National Cancer Institute (NCI) DES Combined Cohort Follow-up Study were queried in 2011 for any history of depression diagnosis or treatment. Hazard ratios (HRs; 95% confidence intervals [CIs]) estimated the associations between prenatal DES exposure and depression risk.

Results: Depression was reported by 993 (26%) exposed and 405 (23%) unexposed women, and 177 (17%) exposed and 181 (17%) unexposed men. Compared with the unexposed, HRs for DES and depression were 1.1 (95% CI = 0.9, 1.2) in women and 1.0 (95% CI = 0.8, 1.2) in men. For medication-treated depression, the HRs (CIs) were 1.1 (0.9, 1.2) in women and 0.9 (0.7, 1.2) in men. In women, the HR (CI) for exposure to a low cumulative DES dose was 1.2 (1.0, 1.4), and for DES exposure before 8 weeks' gestation was 1.2 (1.0, 1.4). In men, the HR for low dose was 1.2 (95% CI = 0.9, 1.6) and there was no association with timing. In women, associations were uninfluenced by the presence of DES-related vaginal epithelial changes or a prior diagnosis of DES-related adverse outcomes.

Conclusions: Prenatal DES exposure was not associated overall with risk of depression in women or men. In women, exposure in early gestation or to a low cumulative dose may be weakly associated with an increased depression risk.
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http://dx.doi.org/10.1097/EDE.0000000000001048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679745PMC
September 2019

Associations of pregnancy-related factors and birth characteristics with risk of endometrial cancer: A Nordic population-based case-control study.

Int J Cancer 2020 03 20;146(6):1523-1531. Epub 2019 Jun 20.

Cancer Registry of Norway, Oslo, Norway.

Many pregnancy-related factors are associated with reduced endometrial cancer risk. However, it remains unclear whether pregnancy-related complications (e.g., hypertensive conditions) are associated with risk and whether these associations vary by endometrial cancer subtype. Thus, we evaluated the risk of endometrial cancer, overall and by subtype, in relation to pregnancy-related factors, pregnancy complications and birth characteristics. Utilizing population-based register data from four Nordic countries, we conducted a nested case-control analysis of endometrial cancer risk. We included 10,924 endometrial cancer cases and up to 10 matched controls per case. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models. We further evaluated associations by individual histology (i.e., endometrioid, serous, etc.) or, for rare exposures (e.g., pregnancy complications), by dualistic type (Type I [n = 10,343] and Type II [n = 581]). Preexisting and pregnancy-related hypertensive conditions were associated with increased endometrial cancer risk (OR [95% CI]: preexisting hypertension 1.88 [1.39-2.55]; gestational hypertension 1.47 [1.33-1.63]; preeclampsia 1.43 [1.30-1.58]), with consistent associations across dualistic type. Increasing number of pregnancies (≥4 vs. 1 birth: 0.64 [0.59-0.69]) and shorter time since last birth (<10 vs. ≥30 years: 0.34 [0.29-0.40]) were associated with reduced endometrial cancer risk, with consistent associations across most subtypes. Our findings support the role for both hormonal exposures and cell clearance as well as immunologic/inflammatory etiologies for endometrial cancer. This research supports studying endometrial hyperplasia, a precursor condition of endometrial cancer, in the context of pregnancy-related exposures, as this may provide insight into the mechanisms by which pregnancy affects subsequent cancer risk.
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http://dx.doi.org/10.1002/ijc.32494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898733PMC
March 2020

Estrogen metabolism pathways in preeclampsia and normal pregnancy.

Steroids 2019 04 25;144:8-14. Epub 2019 Jan 25.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, United States.

Background: Experimental studies suggest that shallow uterine cytotrophoblastic invasion in preeclampsia may be associated with alterations in estrogen metabolism. The objective of this study was to examine the association of parent estrogens and their metabolites between preeclamptics and normotensive controls at three time points during pregnancy. Methods Parent estrogens and their metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry in 66 singleton preeclampsia cases and 137 matched controls. Percent change in geometric means were estimated by general linear models adjusted for gestational age at sampling, maternal age, parity, race, body mass index, and use of assisted reproductive technologies. Results Urinary estradiol concentrations were approximately 50% higher in early pregnancy in preeclampsia cases than controls, but similar late in pregnancy. There was an approximate 20% reduction in total 2-pathway metabolites and 4-pathway metabolites in cases compared with controls in mid- and later pregnancy that was slightly attenuated with adjustment for BMI, and a reduction in 16-pathways in mid-pregnancy but not later. Conclusion(s) Our findings show that estradiol concentrations were elevated in preeclampsia versus controls in early pregnancy. In mid-pregnancy, all three estrogen metabolism (2-, 4-, and 16-) pathways showed some reduction in preeclampsia that appeared to continue for the 2- and 4-pathways in late pregnancy. We hypothesize that this may indicate that there is a generalized reduction in estrogen metabolism in preeclampsia rather than a deficit of specific enzymes, such as those involved in the 2-hydroxylation pathway.
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http://dx.doi.org/10.1016/j.steroids.2019.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681456PMC
April 2019

Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): A report from the US National Cancer Institute DES Third Generation Study.

Reprod Toxicol 2019 03 27;84:32-38. Epub 2018 Dec 27.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, United States.

Background: Animal studies suggest that prenatal exposure to diethylstilbestrol (DES) causes epigenetic alterations in primordial germ cells that affect the next generation, but human studies are sparse.

Methods: We assessed hormonally mediated outcomes in third generation women whose mothers were prenatally DES-exposed and unexposed.

Results: Compared to the unexposed, DES-exposed third generation women had an increased risk of irregular menses and amenorrhea; the respective prevalence ratios and 95% confidence intervals (CI) in follow-up data were 1.32 (95% CI: 1.10, 1.60) and 1.26 (95% CI: 1.06, 1.49); associations were more apparent in third generation women whose prenatally DES-exposed mothers were affected by vaginal epithelial changes. The follow-up data also indicated an association with preterm delivery (relative risk (RR): 1.54; 95% CI: 1.35, 1.75).

Conclusion: DES third generation women may have an increased risk of irregular menstrual cycles, amenorrhea, and preterm delivery, consistent with inter-generational effects of endocrine disrupting chemical exposure in humans.
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http://dx.doi.org/10.1016/j.reprotox.2018.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382553PMC
March 2019

Maternal reproductive hormones and angiogenic factors in pregnancy and subsequent breast cancer risk.

Cancer Causes Control 2019 Jan 1;30(1):63-74. Epub 2018 Dec 1.

Epidemiology and Biostatistics Program, Division of Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.

Purpose: Breast cancer risk associated with pregnancy characteristics may be mediated by maternal hormones or angiogenic factors.

Methods: We conducted a prospective breast cancer case-control study among women in the Avon Longitudinal Study of Parents and Children (ALSPAC) and Norwegian Mother and Child Cohort Study (MoBa) related to maternal pregnancy prolactin (n = 254 cases and 374 controls), placental growth factor (PlGF, n = 252 and 371), soluble fms-like tyrosine kinase-1 (sFlt-1, n = 118 and 240) and steroid hormone concentrations (ALSPAC only, n = 173 and 171). Odds ratios (OR) and 95% confidence intervals (CI) for a 1 SD change in analytes were estimated using unconditional logistic regression with matching factors (cohort, mother's birth year, serum/plasma, blood collection timing) and gestational age.

Results: Breast cancer ORs (95% CI) were 0.85 (0.51-1.43) for estradiol, 0.86 (0.67-1.09) for testosterone, 0.89 (0.71-1.13) for androstenedione, 0.97 (0.71-1.34) for hCG, 0.93 (0.75, 1.15) for prolactin, 1.00 (0.78-1.27) for PlGF and 1.91 (1.00-3.65 ALSPAC) and 0.94 (0.73-1.21 MoBa) for sFlt-1, and were similar adjusting for potential confounders. Results were similar by blood collection timing, parity, age at first birth or diagnosis, and time between pregnancy and diagnosis.

Conclusion: These data do not provide strong evidence of associations between maternal hormones or angiogenic factors with subsequent maternal breast cancer risk.
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http://dx.doi.org/10.1007/s10552-018-1100-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438198PMC
January 2019

Estrogen Metabolism in Postmenopausal Women Exposed to Diethylstilbestrol.

Cancer Epidemiol Biomarkers Prev 2018 10 26;27(10):1208-1213. Epub 2018 Jul 26.

Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, NCI, NIH, Bethesda, Maryland.

Prenatal diethylstilbestrol (DES) exposure is associated with adverse reproductive outcomes and cancer of the breast and vagina/cervix in adult women. DES effects on estrogen metabolism have been hypothesized, but reproductive hormone concentrations and metabolic pathways have not been comprehensively described. Blood samples were provided by 60 postmenopausal women (40 exposed and 20 unexposed) who were participants in the NCI Combined DES Cohort Study, had never used hormone supplements or been diagnosed with cancer, had responded to the most recent cohort study questionnaire, and lived within driving distance of Boston University Medical School (Boston, MA). Parent estrogens and their metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry. Age-adjusted percent changes in geometric means and associated 95% confidence intervals (CIs) between the exposed and unexposed were calculated. Concentrations of total estrogens (15.3%; CI, -4.1-38.5) and parent estrogens (27.1%; CI, -8.2-76.1) were slightly higher in the DES-exposed than unexposed. Ratios of path2:parent estrogens (-36.5%; CI, -53.0 to -14.3) and path2:path16 (-28.8%; CI, -47.3-3.7) were lower in the DES exposed. These associations persisted with adjustment for total estrogen, years since menopause, body mass index, parity, and recent alcohol intake. These preliminary data suggest that postmenopausal women who were prenatally DES exposed may have relatively less 2 than 16 pathway estrogen metabolism compared with unexposed women. Lower 2 pathway metabolism has been associated with increased postmenopausal breast cancer risk and could potentially offer a partial explanation for the modest increased risk observed for prenatally DES-exposed women. .
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170707PMC
October 2018

Pregnancy complications and subsequent breast cancer risk in the mother: a Nordic population-based case-control study.

Int J Cancer 2018 10 10;143(8):1904-1913. Epub 2018 Aug 10.

Cancer Registry of Norway, Oslo, Norway.

Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population-based case-control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967-2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78-0.97), gestational hypertension (OR 0.90; 95% CI 0.86-0.93) and preeclampsia (OR 0.91; 95% CI 0.88-0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98-1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.
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http://dx.doi.org/10.1002/ijc.31600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128759PMC
October 2018

Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women.

Int J Cancer 2018 10 10;143(8):1858-1867. Epub 2018 Jul 10.

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) ≤30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [≥4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), p  < 0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.
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http://dx.doi.org/10.1002/ijc.31581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128744PMC
October 2018

Prenatal diethylstilbestrol exposure and mammographic density.

Int J Cancer 2018 09 2;143(6):1374-1378. Epub 2018 May 2.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

In a prospective cohort study of the health effects associated with prenatal Diethylstilbestrol (DES) exposure, DES was associated with an increased breast cancer risk after 40 years of age. It is unknown whether it is associated with greater mammographic density, which strongly predicts breast cancer risk. A cohort of DES-exposed and unexposed women was assembled at the Mayo Clinic in 1975, and followed through 2012 as part of the National Cancer Institute's DES follow-up study. Mammographic density from 3,637 mammograms for 332 (222 DES-exposed, 110 unexposed) women in this cohort screened at the Mayo Clinic, Rochester between 1996 and 2015 was determined clinically using the Breast Imaging Reporting and Data System (BI-RADS). Any effect of prenatal DES exposure on mammographic density was estimated using repeated measures logistic regression. There was no association between prenatal DES exposure and high mammographic density for either premenopausal [Odds ratios (OR) = 0.92 (95% Confidence Interval (CI): 0.50, 1.7] or postmenopausal women (OR = 0.90; 95% CI: 0.54, 1.5). Among premenopausal women, associations differed by body mass index (BMI), with ORs of 1.47 (0.70, 3.1) for women with BMI above the median and 0.53 (0.23, 1.3) for those with BMI below the median (p  = 0.05). Overall, however, prenatal DES exposure was not associated with high mammographic density in this sample of DES Study participants. Consequently, this study does not provide evidence that high mammographic density is involved with the influence of DES on breast cancer risk.
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http://dx.doi.org/10.1002/ijc.31524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241294PMC
September 2018

Prenatal diethylstilbestrol exposure and cancer risk in women.

Environ Mol Mutagen 2019 06 10;60(5):395-403. Epub 2017 Nov 10.

Slone Epidemiology Unit, Boston University, Boston, Massachusetts.

In the Diethylstilbestrol [DES] Combined Cohort Follow-up, the age- and calendar-year specific standardized incidence ratio [SIR] for clear cell adenocarcinoma [CCA] was 27.6 (95% confidence interval [CI] 7.51-70.6) for the exposed women. The SIR for breast cancer was 1.17 (95% CI 1.01-1.36) and the hazard ratio [HR] adjusted for birth year and cohort for comparison with the unexposed was 1.05 (95% CI 0.79-1.41). The SIR for pancreatic cancer was 2.43 (95% CI 1.21-4.34) and the adjusted HR for comparison with unexposed women was 7.16 (95% CI 0.84-61.5). There was little evidence of excess risk for other sites. There appeared to be a deficit in risk for endometrial cancer among the exposed (SIR 0.61; 95% CI 0.35-0.98), and an excess in the unexposed (SIR 1.55; 95% CI 0.95-2.40); the adjusted HR was 0.45 (95% CI 0.22-0.93) for the internal comparison. There was no overall excess cancer risk in exposed women compared with general population rates (1.06; 95% CI 0.95-1.17) or with unexposed participants (adjusted HR 1.03; 95% CI 0.84-1.25). These data do not support the suggestion that there is a diathesis of cancers in DES exposed female offspring The excess risk of breast and pancreatic cancers that we observed is concerning and warrants continued follow-up and mechanistic investigation. Environ. Mol. Mutagen. 60:395-403, 2019. Published 2017. This article is a US Government work and is in the public domain in the USA.
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http://dx.doi.org/10.1002/em.22155DOI Listing
June 2019

A Prospective Cohort Study of Prenatal Diethylstilbestrol Exposure and Cardiovascular Disease Risk.

J Clin Endocrinol Metab 2018 01;103(1):206-212

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

Purpose: Prenatal exposure to diethylstilbestrol (DES), a prototype endocrine-disrupting chemical, is associated with risk for adverse reproductive outcomes and cancer in women. We investigated whether cardiovascular disease (CVD) risk might also be greater in women prenatally exposed to DES.

Methods: DES-exposed (n = 3941) and -unexposed (n = 1705) women participating in the Combined DES Cohort Follow-up Study were followed prospectively from 1994 to 2013. Prenatal DES exposure (or lack of exposure) was documented in the birth record or physician's note. Participants reported by questionnaire any "serious medical conditions requiring hospitalization, surgery or long-term treatment," including coronary artery disease (CAD), myocardial infarction (MI), and stroke. We sought physician's verification of self-reports and identified CVD deaths from the National Death Index. Hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox proportional hazard regression models estimated associations between DES exposure and CVD incidence, adjusted for birth year, original cohort, and potential confounders.

Results: In comparison of the exposed to the unexposed women, the HRs for reported conditions were 1.74 (95% CI, 1.03 to 2.93) for CAD, 2.20 (95% CI, 1.15 to 4.21) for MI, 1.01 (95% CI, 0.54 to 1.90) for stroke, and 1.31 (95% CI, 0.93 to 1.86) for the combined conditions (i.e., total CVD). The HRs were similar for verified outcomes (CAD, 1.72; MI, 2.67; stroke, 0.92; and total CVD, 1.25) and with additional adjustment for hypertension, diabetes, and high cholesterol (HRs: CAD, 1.67; MI, 2.04; stroke, 0.96; and total CVD, 1.24).

Conclusions: These data demonstrate associations in women who have prenatal DES exposure with CAD and MI, but not with stroke, which appear to be independent of established CVD risk factors.
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http://dx.doi.org/10.1210/jc.2017-01940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761490PMC
January 2018

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy.

Pediatrics 2016 11;138(Suppl 1):S42-S44

Geisel School of Medicine at Dartmouth and the Hood Center for Children and Families, Lebanon, New Hampshire.

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http://dx.doi.org/10.1542/peds.2015-4268GDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080866PMC
November 2016

Prevalence of pregnancy hypertensive disorders in Mongolia.

Pregnancy Hypertens 2016 Oct 7;6(4):413-417. Epub 2016 Oct 7.

Divisions of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9609 Medical Center Drive, Rockville, MD 20850, United States. Electronic address:

Objective: To estimate the prevalence of preeclampsia in a contemporary population of Mongolian women living in urban and rural areas. We determined the sensitivity and specificity of diagnosis based on established diagnostic criteria and assessed whether local diagnostic criteria were similar to those used in the US.

Study Design: Cross-sectional study of urban and nomadic pregnant women recruited in Ulaanbaatar (n=136) and rural provinces (n=85).

Main Outcome Measures: Preeclampsia defined as hypertension new to pregnancy after 20weeks and proteinuria (or protein creatinine ratio ⩾0.3 and dipstick reading>+1) or in the absence of proteinuria, hypertension and onset of: renal insufficiency, impaired liver function, thrombocytopenia, pulmonary edema, cerebral/visual symptoms. Prevalence of preeclampsia based on established criteria was compared with prevalence based on local physician's diagnosis.

Results: Prevalence of local physician diagnosed preeclampsia was 9.5% (13.2% urban, 3.5% rural). Prevalence based on established diagnostic criteria was 4.1% (4.4% urban, 3.5% rural). Sensitivity of physician's diagnosis was 23.8%, specificity was 98.0%, false negative rate was 2.0% and false positive rate was 76.2%. While prevalence based on local physician's diagnosis was over double that based on diagnostic criteria, overdiagnosis did not result in adverse effects. Women fulfilling diagnostic criteria for preeclampsia had babies with higher birth weights than women who did not (p-value=0.006).

Conclusion: The 4.1% prevalence of preeclampsia in Mongolia was consistent with global estimates of 2-8%, suggesting the pathophysiology of preeclampsia here may be similar to that found globally. Sensitivity of physician's diagnosis was low, specificity was high.
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http://dx.doi.org/10.1016/j.preghy.2016.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161111PMC
October 2016

Associations of Breast Cancer Risk Factors with Premenopausal Sex Hormones in Women with Very Low Breast Cancer Risk.

Int J Environ Res Public Health 2016 10 31;13(11). Epub 2016 Oct 31.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Breast cancer incidence rates are low but rising in urban Mongolia. We collected reproductive and lifestyle factor information and measured anthropometrics and serum sex steroid concentrations among 314 premenopausal women living in Ulaanbaatar, Mongolia. Mean differences in hormone concentrations by these factors were calculated using age-adjusted quadratic regression splines. Estrone and estradiol in college-educated women were, respectively, 18.2% ( = 0.03) and 23.6% ( = 0.03) lower than in high-school-educated women. Progesterone concentrations appeared 55.8% lower ( = 0.10) in women residing in modern housing compared with women living in traditional housing (gers), although this finding was not statistically significant. Testosterone concentrations were positively associated with adiposity and central fat distribution % difference for highest vs. lowest quarter for body mass index (17.1% ( = 0.001)) and waist-to-height ratio (15.1% ( = 0.005)). Estrogens were higher in the follicular phase of women who breastfed each child for shorter durations. A distinct hormonal profile was associated with an urban lifestyle in premenopausal, Mongol women. In particular, heavier, more-educated women living in urban dwellings had higher testosterone and lower estrogen and progesterone levels. Higher breast cancer incidence in urban compared with rural women suggest that the hormonal profile associated with a more traditional lifestyle may be protective among Mongol women.
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http://dx.doi.org/10.3390/ijerph13111066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129276PMC
October 2016

Reply.

Am J Obstet Gynecol 2017 02 28;216(2):198-199. Epub 2016 Sep 28.

Department of Epidemiology, Boston University School of Public Health, 715 Albany St, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2016.09.098DOI Listing
February 2017

Reproductive history and risk of colorectal adenocarcinoma in parous women: a Nordic population-based case-control study.

Br J Cancer 2016 Nov 4;115(11):1416-1420. Epub 2016 Oct 4.

Cancer Registry of Norway, Oslo, Norway.

Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history.

Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders.

Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found.

Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.
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http://dx.doi.org/10.1038/bjc.2016.315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129816PMC
November 2016

A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial.

Cancer Causes Control 2016 08 29;27(8):1009-17. Epub 2016 Jun 29.

Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20852, USA.

Purpose: Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed.

Methods: We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55-83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993-2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9-12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER-/PR-. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR.

Results: Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33-2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63-3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19-2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors.

Conclusions: There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1.
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http://dx.doi.org/10.1007/s10552-016-0779-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958123PMC
August 2016