Risk Of Uterine Leiomyomata Research Articles

Genetic contribution of reproductive traits to risk of uterine leiomyomata: a large-scale, genome-wide, cross-trait analysis

BackgroundWhile phenotypic associations between female reproductive characteristics and uterine leiomyomata have long been observed in epidemiological investigations, the shared genetic architecture underlying these complex phenotypes remains unclear. ObjectiveWe aimed to investigate the shared genetic basis, pleiotropic effects, and potential causal relationships underlying reproductive traits (age at menarche, age at natural menopause, and age at first birth) and uterine leiomyomata . Study designUtilizing large-scale genome-wide association studies conducted in women of European ancestry for age at menarche (N = 329,345), age at natural menopause (N = 201,323), age at first birth (N = 418,758), and uterine leiomyomata (Ncases/Ncontrols = 35,474/267,505), we performed a comprehensive genome-wide cross-trait analysis to examine systematically the common genetic influences between reproductive traits and UL. ResultsSignificant global genetic correlations were identified for uterine leiomyomata with age at menarche (rg = –0.17, P = 3.65 × 10–10), age at natural menopause (rg = 0.23, P = 3.26 × 10–07), and age at first birth (rg = –0.16, P = 1.96 × 10–06). Thirteen genomic regions were further revealed as contributing significant local correlations to age at natural menopause and uterine leiomyomata. Cross-trait meta-analysis identified 23 shared loci, three of which were novel. Transcriptome-wide association study found 15 shared genes, targeting tissues of the digestive, exo-/endocrine, nervous, and cardiovascular systems. Mendelian randomization suggested causal relationships of genetically predicted later age at menarche (OR = 0.88, 95% CI = 0.85-0.92, P = 1.50 × 10–10) or later age at first birth (OR = 0.95, 95% CI = 0.90-0.99, P = 0.02) with a reduced risk of uterine leiomyomata, and a causal relationship of genetically predicted later age at natural menopause with an increased risk of uterine leiomyomata (OR = 1.08, 95% CI = 1.06-1.09, P = 2.30 × 10–27). No causal association in the reverse direction was found. ConclusionsOur work highlights substantial shared genetic influences as well as significant causal links underlying reproductive traits and uterine leiomyomata. Findings suggest that early identification of female reproductive risk factors may facilitate the initiation of strategies to modify potential uterine leiomyomata risk.

Exposure to airborne polychlorinated biphenyls and risk of uterine leiomyomata, endometriosis, and PCOS: a register-based Danish cohort study

Exposure to airborne polychlorinated biphenyls and risk of uterine leiomyomata, endometriosis, and PCOS: a register-based Danish cohort study

Risk of uterine leiomyomata with menstrual and reproductive factors in premenopausal women: Korea nurses’ health study

BackgroundUterine leiomyomata (UL) are benign smooth muscle tumors that may cause significant morbidity in women of reproductive age. This study aimed to investigate the relationship of menstrual and reproductive factors with the risk of UL in premenopausal women.MethodsThis prospective study included 7,360 premenopausal women aged 22–48 years who were part of the Korea Nurses’ Health Study. Information on the menstrual cycle and reproductive history was assessed between 2014 and 2016, and self-reported cases of UL were obtained through 2021. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsDuring 32,072 person-years of follow-up, 447 incident cases of UL were reported. After adjusting for other risk factors, women with late age at menarche had a lower incidence of UL (≥ 16 vs. 12–13 years: HR 0.68; 95% CI 0.47–0.99; p for trend = 0.026). The risk of UL was inversely associated with current menstrual cycle length (≥ 40 or too irregular to estimate vs. 26–31 days: HR 0.40; 95% CI 0.24–0.66) and cycle length at ages 18–22 years (HR 0.45; 95% CI 0.31–0.67; p for trend < 0.001, each). Parous women had lower risk of UL than nulliparous women (HR 0.40; 95% CI 0.30–0.53) and women who were aged 29–30 years at first birth had a lower risk of UL than those who were aged ≤ 28 years at first birth (HR 0.58; 95% CI 0.34–0.98). There was no significant association of the number of births or breastfeeding with the risk of UL among parous women. Neither a history of infertility nor oral contraceptive use was associated with the risk of UL.ConclusionsOur results suggest that age at menarche, menstrual cycle length, parity, and age at first birth are inversely associated with the risk of UL in premenopausal Korean women. Future studies are warranted to confirm the long-term effects of menstrual and reproductive factors on women’s health.

Urinary phytoestrogens and the risk of uterine leiomyomata in US women

BackgroundUterine leiomyomata (UL) is a common gynecological disease in women. Studied on the relationship between single metabolites of urinary phytoestrogens and UL, especially for the combined effects of mixed metabolites on UL still are insufficient.MethodsIn this cross-sectional study, we included 1,579 participants from the National Health and Nutrition Examination Survey. Urinary phytoestrogens were assessed by measuring urinary excretion of daidzein, genistein, equol, O-desmethylangolensin, enterodiol and enterolactone. The outcome was defined as UL. Weighted logistic regression was used to analyze the association between single metabolites of urinary phytoestrogens and UL. Notably, we adopted the weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) models, to investigate the combined effects of six mixed metabolites on UL.ResultsThe prevalence of UL was approximately 12.92%. After adjusting age, race/ethnicity, marital status, drinking status, body mass index, waist circumference, menopausal status, ovary removed status, use of female hormones, hormones/hormone modifiers, total energy, daidzein, genistein, O-desmethylangolensin, enterodiol, and enterolactone, the association of equol with UL was significant [Odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.09–3.38]. In the WQS model, mixed metabolites of urinary phytoestrogen had a positive association with UL (OR = 1.68, 95%CI: 1.12–2.51), with the highest weighted chemical of equol. In the gpcomp model, equol had the largest positive weight, followed by genistein and enterodiol. In the BKMR model, equol and enterodiol have positive correlation on UL risk, while enterolactone has negative correlation.ConclusionOur results implied a positive association between the mixed metabolites of urinary phytoestrogen and UL. This study provides evidence that urinary phytoestrogen-metabolite mixture was closely related to the risk of female UL.

Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1 A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.

Familial Predisposition to Leiomyomata: Searching for Protective Genetic Factors.

In order to determine genetic loci associated with decreasing risk of uterine leiomyomata (UL), a genome-wide association study (GWAS) was performed. We analyzed a group of patients with a family history of UL and a control group consisting of patients without uterine fibroids and a family predisposition to this pathology. Six significant single nucleotide polymorphisms were selected for PCR-genotyping of a large data set of patients with UL. All investigated loci (rs3020434, rs11742635, rs124577644, rs12637801, rs2861221, and rs17677069) demonstrated the lower frequency of minor alleles within a group of women with UL, especially in a subgroup consisting of patients with UL and a familial history of leiomyomata. We also found that the minor allele frequencies of these SNPs in our control group were higher than those across the Caucasian population in all. Based on the obtained data, an evaluation of the common risk of UL was performed. Further work will pave the way to create a specific SNP-panel and allow us to estimate a genotype-based leiomyoma incidence risk. Subsequent studies of genetic variability in a group of patients with a familial predisposition to UL will allow us to make the prediction of the development and course of the disease more individualized, as well as to give our patients personalized recommendations about individual reproductive strategies.

Clinical Value of Body Mass Index and Waist-Hip Ratio in Clinicopathological Characteristics and Prognosis of Uterine Leiomyomata.

Objective To explore the relationship between body mass index (BMI) and waist-to-hip ratio (WHR) and clinicopathological characteristics and prognosis of uterine leiomyomata (UL). Methods A retrospective analysis of the clinical data of 133 patients with UL admitted to our hospital from September 2018 to August 2019. According to the BMI standard, the patients were divided into the normal group (n = 32), the super-recombination group (n = 45), and the obesity group (n = 56). According to WHR, the patients were divided into the normal body group (n = 32) and the obesity body group (n = 101). The prognosis of all patients with UL at 3 months postoperatively was evaluated. The relationship between BMI patients and clinical characteristics in different groups was compared, and univariate analysis and multivariate logistic regression model were used to analyze the factors affecting the prognosis of UL patients. Results The proportion of UL patients in the overweight/obese group was higher than that of the normal group, the proportion of the obese body group was higher than that of the normal body group, and the proportion of the good prognosis group was higher than that of the poor prognosis group (P < 0.05). The difference between the overweight/obese group and the normal group and the obese body group and the normal body group was irregular vaginal bleeding, the number of tumors, and the diameter of the lesion (P < 0.05), and the differences between the degenerations in the obese body group and the normal body group were statistically significant (P < 0.05). Multivariate analysis showed that BMI, WHR, surgical method, and tumor location were all independent risk factors that affected the prognosis of the surgery (P < 0.05). Conclusion Elevated BMI and WHR can be accompanied by an increased risk of UL. Obesity is a risk factor for UL. Overweight/obese women are more clinically pathological than normal patients, and overweight/obese patients have worse surgical prognosis than normal patients. In order to reduce the prevalence of UL and improve the clinicopathological characteristics and prognosis of patients, clinically obese women should be instructed to use reasonable diet and exercise to control weight.

A prospective cohort study of ambient air pollution exposure and risk of uterine leiomyomata.

To what extent are ambient concentrations of particulate matter <2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) associated with risk of self-reported physician-diagnosed uterine leiomyomata (UL)? In this large prospective cohort study of Black women, ambient concentrations of O3, but not PM2.5 or NO2, were associated with increased risk of UL. UL are benign tumors of the myometrium that are the leading cause of gynecologic inpatient care among reproductive-aged women. Black women are clinically diagnosed at two to three times the rate of white women and tend to exhibit earlier onset and more severe disease. Two epidemiologic studies have found positive associations between air pollution exposure and UL risk, but neither included large numbers of Black women. We conducted a prospective cohort study of 21998 premenopausal Black women residing in 56 US metropolitan areas from 1997 to 2011. Women reported incident UL diagnosis and method of confirmation (i.e. ultrasound, surgery) on biennial follow-up questionnaires. We modeled annual residential concentrations of PM2.5, NO2 and O3 throughout the study period. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for a one-interquartile range (IQR) increase in air pollutant concentrations, adjusting for confounders and co-pollutants. During 196685 person-years of follow-up, 6238 participants (28.4%) reported physician-diagnosed UL confirmed by ultrasound or surgery. Although concentrations of PM2.5 and NO2 were not appreciably associated with UL (HRs for a one-IQR increase: 1.01 (95% CI: 0.93, 1.10) and 1.05 (95% CI: 0.95, 1.16), respectively), O3 concentrations were associated with increased UL risk (HR for a one-IQR increase: 1.19, 95% CI: 1.07, 1.32). The association was stronger among women age <35 years (HR: 1.26, 95% CI: 0.98, 1.62) and parous women (HR: 1.28, 95% CI: 1.11, 1.48). Our measurement of air pollution is subject to misclassification, as monitoring data are not equally spatially distributed and we did not account for time-activity patterns. Our outcome measure was based on self-report of a physician diagnosis, likely resulting in under-ascertainment of UL. Although we controlled for several individual- and neighborhood-level confounding variables, residual confounding remains a possibility. Inequitable burden of air pollution exposure has important implications for racial health disparities, and may be related to disparities in UL. Our results emphasize the need for additional research focused on environmental causes of UL. This research was funded by the National Cancer Institute (U01-CAA164974) and the National Institute of Environmental Health Sciences (R01-ES019573). L.A.W. is a fibroid consultant for AbbVie, Inc. and accepts in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com and Kindara.com for primary data collection in Pregnancy Study Online (PRESTO). M.J. declares consultancy fees from the Health Effects Institute (as a member of the review committee). The remaining authors declare they have no actual or potential competing financial interests. N/A.

Incidence of uterine leiomyoma in relation to urinary concentrations of phthalate and phthalate alternative biomarkers: A prospective ultrasound study

BackgroundNumerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies. ObjectivesWe examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence. MethodsWe conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23–35 years who were recruited during 2010–2012. We quantified fourteen phthalates and two phthalate alternative [1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH)] biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate [ΣDEHP] and potency-weighted sum of anti-androgenic [WΣAA] biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence. ResultsMost individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.63 (95% CI: 0.40, 1.01) and 0.61 (95% CI: 0.38, 0.96), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥ 30 kg/m2. HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.92 (95% CI: 0.62, 1.35) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.68 (95% CI: 0.38, 1.18) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles for MEHP and ΣDEHP were 1.29 (95% CI: 0.82, 2.06) and 0.96 (95% CI: 0.61, 1.50), respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08). DiscussionIn this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly.

Dietary Fat Intake and Risk of Uterine Leiomyomata: A Prospective Ultrasound Study.

Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced ω-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010-2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and trans-fat were not appreciably associated with UL incidence. Intake of the marine ω-3 polyunsaturated fatty acid, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: hazard ratio=1.49, 95% confidence interval: 1.04, 2.14; P for trend=0.01). Intakes of total marine ω-3 polyunsaturated fatty acids were similarly associated with elevated UL incidence (hazard ratio =1.35, 95% confidence interval: 0.94, 1.93; P for trend=0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association.

Urinary concentrations of phthalate biomarkers in relation to uterine leiomyomata risk

PDS 62: Chemicals and metals: exposure and biomarkers, Johan Friso Foyer, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background/Aim: Animal and epidemiologic studies suggest that phthalates have adverse reproductive effects. However, the association of phthalates with risk of uterine leiomyomata (UL), hormone-dependent neoplasms, is inconsistent. Only cross-sectional and case-control studies have been conducted to date. Methods: We conducted a prospective case-cohort study of urinary phthalate metabolites with UL incidence in the Study of the Environment, Lifestyle, and Fibroids (SELF), a cohort of premenopausal Black women aged 23-35 residing in Detroit, Michigan. Participants underwent transvaginal ultrasound examinations to identify UL at baseline and follow-up (20, 40 and 60 months). The Centers for Disease Control measured eight urinary phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP) in a random sample selected at baseline and all incident UL cases through 60 months (n=764). We modeled cumulatively-averaged creatinine-adjusted metabolites (i.e., baseline, 20 and 40 month samples). We examined individual metabolites and the total molar sum of di(2-ethylhexyl) phthalate metabolites [ΣDEHP(MEHP+MEHHP+MEOHP+MECPP)]. Cox regression models used cumulatively-averaged quartiles to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusting for potential confounders. Results: We detected phthalate metabolites in the baseline urine of 91-100% of participants. Metabolites were weakly to highly correlated (Spearman correlations=0.19-0.97). We observed a protective association of MiBP and UL, with an adjusted IRR comparing highest vs. lowest quartiles of 0.71 (95% CI: 0.51-0.97), but found varying associations with other individual metabolites (IRRs ranging from 0.80 to 1.14). Adjusted IRRs (95% CIs) comparing ΣDEHP quartiles 2, 3, and 4 (highest) vs. 1 (lowest) were 0.92 (0.67-1.26), 0.62 (0.44-0.87), and 0.80 (0.58-1.10), respectively. Models using baseline concentrations produced comparable findings. Conclusions: In this prospective cohort of reproductive-aged Black women, individual and ΣDEHP molar sum phthalate metabolites were not strongly associated with UL risk.

Plasma concentrations of brominated flame retardants and risk of uterine leiomyomata

Plasma concentrations of brominated flame retardants and risk of uterine leiomyomata

Serum Concentrations of Polychlorinated Biphenyls and Risk of Uterine Leiomyomata

Serum Concentrations of Polychlorinated Biphenyls and Risk of Uterine Leiomyomata

Uterine leiomyomata: a retrospective study of correlations with hypertension and diabetes mellitus from the Japan Nurses’ Health Study

We performed a scrutiny survey of self-reported uterine leiomyomata (UL) to investigate the associations of parental history with hypertension and personal history of hypertension in the UL cases in Japanese women. Questionnaires that included items on the sites of UL determined by imaging techniques and surgical procedure were mailed to 2015 women with a self-reported UL at a baseline survey of the Japan Nurses’ Health Study (n = 15,019). We found that women with a past history and a maternal history of hypertension had an increase in their risk of UL. A maternal history of hypertension was significantly associated with an increase in the risk of UL in women without a past history of hypertension but not in the women with a past history of hypertension. A past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL. Women of reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL.Impact StatementWhat is already known on this subject? A positive association of uterine leiomyomata (UL) with a past history of hypertension has been found but the association of a parental history of hypertension with UL has not yet been clarified.What do the results of this study add? Maternal hypertension, as well as a personal history of hypertension, was associated with an increased risk of UL and a past history and a parental history of diabetes mellitus were not associated with an increase in the risk of UL.What are the implications of these findings for clinical practice and/or further research? Women of a reproductive age with a maternal history of hypertension may be at a higher risk for hypertension and UL.

FASN, dietary fat intake, and risk of uterine leiomyomata in the Black Women's Health Study

To replicate results from a previous genome-wide association study of European ancestry women, in which a positive association was found between uterine leiomyomata (UL) and rs4247357, a single-nucleotide polymorphism located near the fatty acid synthase (FASN) gene. Prospective cohort study. Not applicable. African-American women aged 23-50years, who were premenopausal and had an intact uterus in1997. None. We genotyped rs4247357 among 2,301 incident UL cases and 3,005 controls from the Black Women's Health Study (1997-2011). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age, geographic region of residence, and percent European ancestry using a panel of validated ancestry informative markers. Overall, rs4247357 was not associated with UL risk. Relative to the CC genotype, ORs were 1.04 (95% CI 0.92-1.19) for the AC genotype and 1.09 (95% CI 0.93-1.29) for the AA genotype. A positive association was found, however, among those with higher European ancestry (≥40%). Relative to the CC genotype, ORs were 2.03 (95% CI 1.12-3.69) for the AC genotype and 2.44 (95% CI 1.20-4.96) for the AA genotype. Dietary fat intake also appeared to modify the FASN-UL association. Although there was little overall association between rs4247357 and UL risk, a positive association was observed among women with ≥40% European ancestry. Direct sequencing of this genomic region might be warranted to determine whether rs4247357, or some other variant, is causally related to UL.

Vitamin D and uterine leiomyoma among a sample of US women: Findings from NHANES, 2001–2006

Scientific understanding of the etiology of uterine leiomyomata (UL) remains incomplete, but recent investigations have suggested an association between low Vitamin D and UL risk. In this study, we conducted a cross-sectional analysis of Vitamin D exposure, measured using serum levels of 25(OH)D (a Vitamin D metabolite), and self-reported UL diagnosis among 3590 women aged 20-54 in the National Health and Nutrition Examination Survey (NHANES 2001-2006). Multivariate logistic regression models comparing each quartile of 25(OH)D to the lowest quartile indicated no relationship between 25(OH)D and odds of UL in the whole population (Ptrend=0.37), or in sensitivity analyses. However, a probabilistic analysis correcting outcome misclassification indicated that insufficient 25(OH)D was associated with UL in white (Odds ratio (OR) median estimate: 2.17; 2.5, 97.5 percentiles: (1.26, 23.47)), but not black women (OR median estimate: 1.70; 2.5, 97.5 percentiles: (0.89, 3.51)), suggesting misclassification may have driven some of the null findings.

Depressive symptoms and risk of uterine leiomyomata

Uterine leiomyomata (UL) are a major source of gynecologic morbidity and the primary indication for hysterectomy. Depression can cause dysregulation of the hypothalamic-pituitary-adrenal axis, which may affect the synthesis of reproductive hormones involved in UL pathogenesis. We assessed the association between depressive symptoms and UL among 15,963 premenopausal women. Data were derived from the Black Women's Health Study, a prospective cohort study. In 1999 and 2005, the Center for Epidemiologic Studies Depression Scale (CES-D) was used to ascertain depressive symptoms. On biennial follow-up questionnaires from 1999 through 2011, women reported physician-diagnosed depression, antidepressant use, and UL diagnoses. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. There were 4722 incident UL cases diagnosed by ultrasound (n=3793) or surgery (n=929) during 131,262 person-years of follow-up. Relative to baseline CES-D scores<16, IRRs were 1.05 (95% CI, 0.98-1.13) for CES-D scores 16-24 and 1.16 (95% CI, 1.06-1.27) for CES-D scores≥25 (P-trend=.001). IRRs for current and past physician-diagnosed depression relative to no depression were 1.15 (95% CI, 0.98-1.34) and 1.25 (95% CI, 1.13-1.39), respectively. Results persisted after further control for antidepressant use. IRRs for current and past use of antidepressants (any indication) relative to never use were 1.11 (95% CI, 0.97-1.28) and 1.32 (95% CI, 1.14-1.52), respectively. In this cohort of black women, greater depressive symptoms were associated with UL, independent of antidepressant use, supporting the hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis increases UL risk.

Air pollution and risk of uterine leiomyomata.

Air pollution, particularly from vehicle exhaust, has been shown to influence hormonal activity. However, it is unknown whether air pollution exposure is associated with the occurrence of uterine leiomyomata, a hormonally sensitive tumor of the uterus. For 85,251 women 25-42 years of age at enrollment in the Nurses' Health Study II, we examined proximity to major roadways and outdoor levels of particulate matter less than 10 microns (PM10) or 2.5 microns (PM2.5) or between 10 and 2.5 microns (PM10-2.5) in diameter for all residential addresses from September 1989 to May 2007. To be eligible for this analysis, a woman had to be alive and respond to questionnaires, premenopausal with an intact uterus, and without diagnoses of cancer or prevalent uterine leiomyomata. Incidence of ultrasound- or hysterectomy-confirmed uterine leiomyomata and covariates were reported on biennial questionnaires sent through May 2007. Multivariable time-varying Cox proportional hazard models were used to estimate the relationship between distance to road or PM exposures and uterine leiomyomata risk. During 837,573 person-years of follow-up, there were 7760 incident cases of uterine leiomyomata. Living close to a major road and exposures to PM10 or PM10-2.5 were not associated with an increased risk of uterine leiomyomata. However, each 10 μg/m increase in 2-year average, 4-year average, or cumulative average PM2.5 was associated with an adjusted hazard ratio of 1.08 (95% confidence interval = 1.00-1.17), 1.09 (0.99-1.19), and 1.11 (1.03-1.19), respectively. Chronic exposure to PM2.5 may be associated with a modest increased risk of uterine leiomyomata.

FASN and risk of uterine leiomyomata in African American women

The incidence of uterine leiomyomata (UL) is 2-3 times higher among African Americans than European Americans. In a recent genome-wide association study (GWAS) among women of European descent, a single nucleotide polymorphism (SNP), rs4247357, reached genome-wide significance in association with UL. This SNP is located on chromosome 17 in a large linkage disequilibrium (LD) block that contains three genes, fatty-acid synthase (FASN), coiled-coil-domain-containing 57 (CCDC57), and solute carrier family 16, member 3 (SLC16A3).

Polymorphisms in vitamin D–related genes and risk of uterine leiomyomata

To investigate uterine leiomyomata (UL) incidence in relation to polymorphisms in genes involved in vitamin D metabolism and skin pigmentation. Rates of UL are 2-3 times higher in African Americans than in European Americans. Recent studies suggest that vitamin D deficiency is associated with an increased risk of UL. Nested case-control study. Not applicable. Two thousand two hundred thirty-two premenopausal women first diagnosed with UL confirmed by ultrasound or surgery during 1997-2011 (cases) and 2,432 premenopausal women never diagnosed with UL through 2011 (controls). None. Self-reported UL. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between each polymorphism and UL, controlling for age, geographic region, and ancestry. Three of 12 polymorphisms were associated with UL at the nominal significance level: rs4944957 and rs12800438 near DHCR7 and rs6058017 in ASIP. After correction for multiple hypothesis testing, two single nucleotide polymorphisms remained significantly associated with UL (rs12800438 and rs6058017). Compared with the AA genotype for rs12800438 (correlated with higher serum 25[OH]D levels), ORs were 1.09 (95% CI, 0.92, 1.29) and 1.23 (95% CI, 1.03, 1.47) for the GA and GG genotypes, respectively. Compared with the AA genotype for rs6058017 (correlated with lighter skin pigmentation), ORs were 1.01 (95% CI, 0.83, 1.22) and 1.18 (95% CI, 0.97, 1.44) for the GA and GG genotypes, respectively. Our data support the hypothesis that vitamin D deficiency is involved in UL etiology.