Prospective Study of Ambient Particulate Matter Exposure and Risk of Pulmonary Embolism in the Nurses’ Health Study Cohort

Background

Pulmonary embolism (PE) is the most serious manifestation of venous thromboembolism and a leading cause of sudden death. Several studies have suggested associations of venous thromboembolism with short-term particulate matter (PM) exposure; evidence on long-term PM and traffic exposure is mixed.

Objectives

We examined the association of long-term exposure to PM_2.5, PM_2.5–10, and PM₁₀ (PM with diameter of ≤ 2.5, 2.5–10, and ≤ 10 μm) and distance to roadways with overall incident PE and with PE subtypes in a cohort of U.S. women.

Methods

The study included 115,745 women from the Nurses’ Health Study, followed from 1992 through 2008. Incident PE cases were self-reported biennially. Nonidiopathic PE were cases for which the medical record revealed an underlying health condition related to PE (i.e., surgery, trauma, or malignancy); idiopathic PE were cases with no such history. We used spatiotemporal models combining spatial smoothing and geographic covariates to quantify exposure at residential addresses, and Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CIs).

Results

PM_2.5 averaged over 1 month (HR = 1.22; 95% CI: 1.04, 1.44) or 12 months (HR = 1.17; 95% CI: 0.93, 1.48) was associated with incident PE, after adjusting for known risk factors and PM_2.5–10. Equivalent analyses restricted to PE subtypes showed a positive association for PM_2.5 with nonidiopathic PE, but not with idiopathic PE. We did not find evidence of an association between distance to roadways and PE risk.

Conclusions

We provide evidence that PM in the prior 1 and 12 months is associated with PE risk. Our results also suggest that women with underlying health conditions may be more susceptible to PE after PM exposure.

Citation

Pun VC, Hart JE, Kabrhel C, Camargo CA Jr, Baccarelli AA, Laden F. 2015. Prospective study of ambient particulate matter exposure and risk of pulmonary embolism in the Nurses’ Health Study cohort. Environ Health Perspect 123:1265–1270; http://dx.doi.org/10.1289/ehp.1408927     

Particulate Matter Air Pollution Exposure,Distance to Road,and Incident Lung Cancer in the Nurses’ Health Study Cohort

Background: A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants.Objective: We examined the relation of lung cancer incidence with long-term residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures.Methods: For participants in the Nurses’ Health Study, a nationwide prospective cohort of women, we estimated 72-month average exposures to PM_2.5, PM_2.5–10, and PM₁₀ and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined.Results: During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10-μg/m³ increase in 72-month average PM₁₀ [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM_2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM_2.5–10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM_2.5 (PM₁₀: HR = 1.15; 95% CI: 1.00, 1.32; PM_2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM_2.5–10: HR = 1.11; 95% CI: 0.90, 1.37). Results were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent.Conclusions: Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers.Citation: Puett RC, Hart JE, Yanosky JD, Spiegelman D, Wang M, Fisher JA, Hong B, Laden F. 2014. Particulate matter air pollution exposure, distance to road, and incident lung cancer in the Nurses’ Health Study Cohort. Environ Health Perspect 122:926–932; http://dx.doi.org/10.1289/ehp.1307490     

Cumulative Lead Exposure and Age at Menopause in the Nurses’ Health Study Cohort

Background: Early menopause has been associated with many adverse health outcomes, including increased risk of cardiovascular disease morbidity and mortality. Lead has been found to be adversely associated with female reproductive function, but whether exposures experienced by the general population are associated with altered age at menopause has not been explored.Objective: Our goal was to assess the association between cumulative lead exposure and age at natural menopause.Methods: Self-reported menopausal status and bone lead concentration measured with K-shell X-ray fluorescence—a biomarker of cumulative lead exposure—were obtained from 434 women participants in the Nurses’ Health Study.Results: The mean (± SD) age at natural menopause was 50.8 ± 3.6 years. Higher tibia lead level was associated with younger age at menopause. In adjusted analyses, the average age of menopause for women in the highest tertile of tibia lead was 1.21 years younger (95% CI: –2.08, –0.35) than for women in the lowest tertile (p-trend = 0.006). Although the number of cases was small (n = 23), the odds ratio for early menopause (< 45 years of age) was 5.30 (95% CI: 1.42, 19.78) for women in the highest tertile of tibia lead compared with those in the lowest tertile (p-trend = 0.006). There was no association between patella or blood lead and age at menopause.Conclusions: Our results support an association between low-level cumulative lead exposure and an earlier age at menopause. These data suggest that low-level lead exposure may contribute to menopause-related health outcomes in older women through effects on age at menopause.Citation: Eum KD, Weisskopf MG, Nie LH, Hu H, Korrick SA. 2014. Cumulative lead exposure and age at menopause in the Nurses’ Health Study Cohort. Environ Health Perspect 122:229–234; http://dx.doi.org/10.1289/ehp.1206399     

Mortality in the Medicare Population and Chronic Exposure to Fine Particulate Air Pollution in Urban Centers (2000–2005)

Background

Prospective cohort studies constitute the major source of evidence about the mortality effects of chronic exposure to particulate air pollution. Additional studies are needed to provide evidence on the health effects of chronic exposure to particulate matter ≤ 2.5 μm in aerodynamic diameter (PM_2.5) because few studies have been carried out and the cohorts have not been representative.

Objectives

This study was designed to estimate the relative risk of death associated with long-term exposure to PM_2.5 by region and age groups in a U.S. population of elderly, for the period 2000–2005.

Methods

By linking PM_2.5 monitoring data to the Medicare billing claims by ZIP code of residence of the enrollees, we have developed a new retrospective cohort study, the Medicare Cohort Air Pollution Study. The study population comprises 13.2 million participants living in 4,568 ZIP codes having centroids within 6 miles of a PM_2.5 monitor. We estimated relative risks adjusted by socioeconomic status and smoking by fitting log-linear regression models.

Results

In the eastern and central regions, a 10-μg/m³ increase in 6-year average of PM_2.5 is associated with 6.8% [95% confidence interval (CI), 4.9–8.7%] and 13.2% (95% CI, 9.5–16.9) increases in mortality, respectively. We found no evidence of an association in the western region or for persons ≥ 85 years of age.

Conclusions

We established a cohort of Medicare participants for investigating air pollution and mortality on longer-term time frames. Chronic exposure to PM_2.5 was associated with mortality in the eastern and central regions, but not in the western United States.     

Urban-Rural Differences in Coronary Heart Disease Mortality in the United States: 1999–2009

Objective

Coronary heart disease (CHD) mortality has declined in the past few decades; however, it is unclear whether the reduction in CHD deaths has been similar across urbanization levels and in specific racial groups. We describe the pattern and magnitude of urban-rural variations in CHD mortality in the U.S.

Methods

Using data from the National Center for Health Statistics, we examined trends in death rates from CHD from 1999 to 2009 among people aged 35–84 years, in each geographic region (Northeast, Midwest, West, and South) and in specific racial-urbanization groups, including black and white people in large and medium metropolitan (urban) areas and in non-metropolitan (rural) areas. We also examined deaths from early-onset CHD in females aged <65 years and males aged <55 years.

Results

From 1999 to 2009, there was a 40% decline in age-adjusted CHD mortality. The trend was similar in black and white people but was more pronounced in urban than in rural areas, resulting in a crossover in 2007, when rural areas began showing a higher CHD mortality than urban areas. White people in large metropolitan areas had the largest decline (43%). Throughout the study period, CHD mortality remained higher in black people than in white people, and, in the South, it remained higher in rural than in urban areas. For early-onset CHD, the mortality decline was more modest (30%), but overall trends by urbanization and region were similar.

Conclusion

Favorable national trends in CHD mortality conceal persisting disparities for some regions and population subgroups (e.g., rural areas and black people).Coronary heart disease (CHD) is the leading cause of death for most racial groups in the United States, accounting for approximately 600,000 total deaths annually.¹ CHD remains the leading cause of morbidity and mortality despite the fact that CHD death rates have declined by more than 30% since the 1990s.² This decline has been attributed to a combination of primary and secondary prevention efforts, with a reduction in the level of risk factors, such as blood pressure, smoking, and blood cholesterol, and continuing improvements in diagnosis and treatment.^3–6Although encouraging, the overall decline in CHD mortality rates in the U.S. may conceal less favorable trends in certain regions and demographic groups. Urbanization level is a key characteristic when studying health disparities. One-fifth of the U.S. population resides in rural areas, which rank poorly on 21 of 23 selected population health indicators, behaviors, and risk factors.^7–9 Urban-rural differences provide opportunities for optimizing health-care resources and improving prevention targeting areas of highest need.Few previous studies have described regional differences in CHD mortality in the U.S. and trends over time in recent years.^10–12 There is an ongoing need to monitor the distribution of death rates from specific causes to help reduce preventable diseases and deaths and improve the health of all groups.¹³ This study describes the pattern and magnitude of urban-rural differences in CHD mortality rates by geographic region in the U.S. from 1999 to 2009. The extent to which the decline applies to early CHD mortality is also examined. Deaths from early-onset CHD translate into a large number of years of potential life lost with substantial impact on families and society. Thus, the study of potential determinants of early-onset CHD is important but often neglected.     

A Prospective Analysis of Airborne Metal Exposures and Risk of Parkinson Disease in the Nurses’ Health Study Cohort

Background: Exposure to metals has been implicated in the pathogenesis of Parkinson disease (PD).Objectives: We sought to examine in a large prospective study of female nurses whether exposure to airborne metals was associated with risk of PD.Methods: We linked the U.S. Environmental Protection Agency (EPA)’s Air Toxics tract-level data with the Nurses’ Health Study, a prospective cohort of female nurses. Over the course of 18 years of follow-up from 1990 through 2008, we identified 425 incident cases of PD. We examined the association of risk of PD with the following metals that were part of the first U.S. EPA collections in 1990, 1996, and 1999: arsenic, antimony, cadmium, chromium, lead, manganese, mercury, and nickel. To estimate hazard ratios (HRs) and 95% CIs, we used the Cox proportional hazards model, adjusting for age, smoking, and population density.Results: In adjusted models, the HR for the highest compared with the lowest quartile of each metal ranged from 0.78 (95% CI: 0.59, 1.04) for chromium to 1.33 (95% CI: 0.98, 1.79) for mercury.Conclusions: Overall, we found limited evidence for the association between adulthood ambient exposure to metals and risk of PD. The results for mercury need to be confirmed in future studies.Citation: Palacios N, Fitzgerald K, Roberts AL, Hart JE, Weisskopf MG, Schwarzschild MA, Ascherio A, Laden F. 2014. A prospective analysis of airborne metal exposures and risk of Parkinson disease in the Nurses’ Health Study Cohort. Environ Health Perspect 122:933–938; http://dx.doi.org/10.1289/ehp.1307218     

Air Pollution Exposures During Adulthood and Risk of Endometriosis in the Nurses’ Health Study II

Background: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis.Objective: Our goal was to determine the association of air pollution exposures during adulthood, including distance to road, particulate matter < 2.5 μm, between 2.5 and 10 μm, and < 10 μm, (PM_2.5, PM_10–2.5, PM₁₀), and timing of exposure with risk of endometriosis in the Nurses’ Health Study II.Methods: Proximity to major roadways and outdoor levels of PM_2.5, PM_10–2.5, and PM₁₀ were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk.Results: Among 84,060 women, 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association between endometriosis risk and distance to road or exposure to PM_2.5, PM_10–2.5, or PM₁₀ averaged over follow-up or during the previous 2- or 4-year period.Conclusions: Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women.Citation: Mahalingaiah S, Hart JE, Laden F, Aschengrau A, Missmer SA. 2014. Air pollution exposures during adulthood and risk of endometriosis in the Nurses’ Health Study II. Environ Health Perspect 122:58–64; http://dx.doi.org/10.1289/ehp.1306627     

Impact of smoking and smoking cessation on health-related quality of life in women in the Nurses’ Health Study

Purpose

To examine the relationship between smoking and health-related quality of life (HRQOL) and the impact of quitting smoking on changes in HRQOL among women in the two Nurses’ Health Study (NHS) cohorts (n = 158,736) who were 29 to 71 years of age in 1992/1993 when they reported data on smoking status and completed the Short Form-36^® version 1 (SF-36^®).

Methods

At baseline, the SF-36^® physical component scores (SF-PCS) and mental component scores (SF-MCS) were examined by smoking status (never, 56%, former, 32%, and current, 13%) within 10-year age groups. Smoking characteristics were analyzed as correlates of SF-36^®. Changes in smoking status and SF-PCS and SF-MCS, adjusted for comorbid disease and other covariates, were reassessed at 4-year intervals among current smokers in 1992/1993 and those who either continued smoking after 4 and 8 years or reported not smoking at both intervals.

Results

Smokers had lower HRQOL (SF-PCS and SF-MCS) as compared to never and former smokers. Current smoking, cigarettes per day and time since quitting were associated with significantly lower SF-PCS and SF-MCS. Continuing smokers and those who quit had significant declines in SF-PCS over time and significant improvements in SF-MCS at 8 years. There was minimal difference between groups, with some greater improvements in SF-MCS among those reporting non-smoking at 8 years. These findings support the lower ratings of HRQOL by smokers, but quitting alone, after an average of 21 years of smoking, did not improve HRQOL. Further study focused on the HRQOL impact of quitting smoking is needed.     

Reproductive Factors and Risk of Thyroid Cancer in Women: An Analysis in the Nurses’ Health Study II

BackgroundThe incidence of thyroid cancer in women is increasing at an alarming rate, with greatest risk in the reproductive years. Establishing relationships of hormonally related reproductive factors with thyroid cancer has been difficult. We aimed to elucidate potential risk factors for thyroid cancer in a large cohort of women.MethodsAmong 116,228 women in the Nurses’ Health Study II followed from 1989 to 2013, 620 cases of thyroid cancer were identified. We examined reproductive and hormone-related factors, including age at menarche, age at menopause, parity, oral contraceptive use, and postmenopausal hormone therapy use. Pregnancy, reproductive years, and months of breastfeeding were used as surrogate markers for exposure to endogenous reproductive hormones. We used multivariable Cox models to calculate relative risks and 95% confidence intervals for the associations between these factors and risk of thyroid cancer.ResultsNumber of reproductive years of 41 years or more was associated with more than double the risk of thyroid cancer compared with 30 years or fewer (relative risk, 2.20; 95% confidence interval, 1.19–4.06). The other variables analyzed (parity number, months of breastfeeding, age at menarche, menopausal status, and postmenopausal hormone therapy) were not associated with the risk of thyroid cancer. Women who entered menopause at age 45 years or older had a higher risk of thyroid cancer compared with women who entered menopause at a younger age. This result did not reach statistical significance; however, there was a linear trend between later age at menopause and increased risk of thyroid cancer (p_trend = .009).ConclusionsThis study used a unique large, longitudinal dataset to assess thyroid cancer risk factors and potential confounders over an extended time frame. Our key finding suggests increased risk of thyroid cancer may be associated with a variety of indicators of longer reproductive years. The Nurses’ Health Study II has provided new insights into the hormonal risks associated with thyroid cancer.     

A Study of the Relationship between Health and Subjective Well-Being in Parkinson’s Disease Patients

ObjectivesGovernments are turning their attention to evidence on subjective measures of well-being to inform policy decisions. In the context of health, there is, therefore, growing interest in understanding how measures of health-related quality of life relate to subjective well-being and whether subjective well-being could provide a basis for resource allocation decisions in the future. This study investigates the relationship between health-related quality of life, as measured by the EuroQol five-dimensional (EQ-5D) questionnaire, and subjective well-being in Parkinson’s disease.MethodsA paper questionnaire including the EQ-5D questionnaire, four key subjective well-being questions taken from the Integrated Household Survey in England, and other demographic details was distributed to people with Parkinson’s disease in the United Kingdom. Responses were used to estimate multiple regression models explaining subjective well-being using the EQ-5D questionnaire index (UK weights), EQ-5D questionnaire dimensions and the visual analogue scale, and patients’ sociodemographic characteristics.ResultsA total of 199 responses were received. Combining visual analogue scale and EQ-5D questionnaire dimensions, especially anxiety/depression and, to a lesser extent, mobility, yielded the best-fitting models (adjusted R² range 0.36–0.53). Patients with Parkinson’s disease living in care homes report lower levels of subjective well-being than do those living alone. These effects are not captured by the health-related quality-of-life measures in the analysis.ConclusionsUsual health-related quality-of-life measures can partially explain different well-being dimensions, yet they fail to capture part of the broader impact of disease on subjective well-being. Further empirical research into the relationship between subjective well-being and the EQ-5D Parkinson’s disease longitudinally, and in different disease areas, is required, and further standardization of subjective well-being measures is recommended.     

Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants

Objective: Air pollution contains many toxicants known to affect neurological function and to have effects on the fetus in utero. Recent studies have reported associations between perinatal exposure to air pollutants and autism spectrum disorder (ASD) in children. We tested the hypothesis that perinatal exposure to air pollutants is associated with ASD, focusing on pollutants associated with ASD in prior studies.Methods: We estimated associations between U.S. Environmental Protection Agency–modeled levels of hazardous air pollutants at the time and place of birth and ASD in the children of participants in the Nurses’ Health Study II (325 cases, 22,101 controls). Our analyses focused on pollutants associated with ASD in prior research. We accounted for possible confounding and ascertainment bias by adjusting for family-level socioeconomic status (maternal grandparents’ education) and census tract–level socioeconomic measures (e.g., tract median income and percent college educated), as well as maternal age at birth and year of birth. We also examined possible differences in the relationship between ASD and pollutant exposures by child’s sex.Results: Perinatal exposures to the highest versus lowest quintile of diesel, lead, manganese, mercury, methylene chloride, and an overall measure of metals were significantly associated with ASD, with odds ratios ranging from 1.5 (for overall metals measure) to 2.0 (for diesel and mercury). In addition, linear trends were positive and statistically significant for these exposures (p < .05 for each). For most pollutants, associations were stronger for boys (279 cases) than for girls (46 cases) and significantly different according to sex.Conclusions: Perinatal exposure to air pollutants may increase risk for ASD. Additionally, future studies should consider sex-specific biological pathways connecting perinatal exposure to pollutants with ASD.     

Sexual Function among Women in Midlife: Findings from the Nurses’ Health Study II

BackgroundWomen's sexual well-being is an important determinant of overall health and quality of life across the life course. Yet the factors associated with women's levels of sexual activity and sexual function in midlife are little understood. This study sought to assess the prevalence of recent sexual activity and sexual dysfunction symptoms among middle-aged women and evaluate the associations of partner status, menopause, and health status factors with sexual dysfunction.MethodsParticipants of this cross-sectional study were 68,131 women who responded to the 2013 Nurses’ Health Study II observational cohort questionnaire when they were age 48–68 years. Sexual activity and dysfunction symptoms were assessed with the Female Sexual Function Index. Age-adjusted multivariable regression models estimated risk ratios for the association of health-related factors with past month sexual dysfunction symptoms among women who were sexually active over the past month, overall and stratified by partner status.ResultsOf middle-aged women participants, 73% were sexually active (n = 49,701) and 50% of sexually active women reported symptoms of sexual dysfunction. Symptoms of sexual dysfunction were less common among unpartnered than partnered women (42% vs. 51%; p < .0001). A positive association between menopause and sexual dysfunction was greater for unpartnered women (risk ratio, 2.37, 2.99; p < .001) than partnered women (risk ratio, 1.89, 2.00; p < .001).ConclusionsDifficulty with sexual function is common among women in midlife, but less so than previously estimated. Regular monitoring of women's sexual function could enable clinicians to offer women timely, supportive interventions tailored by partner status and menopausal status.     

Autism Spectrum Disorder and Particulate Matter Air Pollution before,during, and after Pregnancy: A Nested Case–Control Analysis within the Nurses’ Health Study II Cohort

Background

Autism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet has unclear etiology.

Objective

We explored the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child.

Methods

We conducted a nested case–control study of participants in the Nurses’ Health Study II (NHS II), a prospective cohort of 116,430 U.S. female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants’ children born 1990–2002 with ASD (n = 245), and children without ASD (n = 1,522) randomly selected using frequency matching for birth years. Diagnosis of ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤ 2.5 μm (PM_2.5) and 2.5–10 μm (PM_10–2.5) were predicted from a spatiotemporal model for the continental United States and linked to residential addresses.

Results

PM_2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range (IQR) higher PM_2.5 (4.42 μg/m³) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM_2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, whereas the association with the 9 months of pregnancy remained (OR = 1.63; 95% CI: 1.08, 2.47). The association between ASD and PM_2.5 was stronger for exposure during the third trimester (OR = 1.42 per IQR increase in PM_2.5; 95% CI: 1.09, 1.86) than during the first two trimesters (ORs = 1.06 and 1.00) when mutually adjusted. There was little association between PM_10–2.5 and ASD.

Conclusions

Higher maternal exposure to PM_2.5 during pregnancy, particularly the third trimester, was associated with greater odds of a child having ASD.

Citation

Raz R, Roberts AL, Lyall K, Hart JE, Just AC, Laden F, Weisskopf MG. 2015. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case–control analysis within the Nurses’ Health Study II cohort. Environ Health Perspect 123:264–270; http://dx.doi.org/10.1289/ehp.1408133     

Inflammation, coagulation and risk of locomotor disability in elderly women: findings from the British Women’s Heart and Health Study

This study investigated associations between chronic inflammation and coagulation and incident locomotor disability using prospective data from the British Women's Heart and Health Study. Locomotor disability was assessed using self-reported questionnaires in 1999/2000, and 3 and 7?years later. Scores for inflammation and coagulation were obtained from summation of quartile categories of all available biomarkers from blood samples taken at baseline. 534 women developed locomotor disability after 3?years, 260 women after 7?years, while 871 women remained free of locomotor disability over the whole study period. After adjustment for demographic characteristics, lifestyle factors and health conditions, we found associations between inflammation and incident locomotor disability after three (OR per unit increase in score?=?1.08, 95?% confidence interval (CI): 1.03, 1.13) and 7?years (OR?=?1.10, 95?% CI: 1.03, 1.18) and between coagulation and incident locomotor disability after 3 (OR?=?1.06, 95?% CI: 0.98, 1.14) and 7?years (OR?=?1.09, 95?% CI: 1.00, 1.18). This corresponds to ORs between 1.8 and 2.4 comparing women with highest to lowest inflammation or coagulation scores. These results support the role of inflammation and coagulation in the development of locomotor disability in elderly women irrespective of their lifestyle factors and underlying age-related chronic diseases.     

Dietary Cadmium Exposure and Risk of Breast,Endometrial, and Ovarian Cancer in the Women’s Health Initiative

Background: In vitro and animal data suggest that cadmium, a heavy metal that contaminates some foods and tobacco plants, is an estrogenic endocrine disruptor. Elevated estrogen exposure is associated with breast, endometrial, and ovarian cancer risk.Objectives: We examined the association between dietary cadmium intake and risk of these cancers in the large, well-characterized Women’s Health Initiative (WHI).Methods: A total of 155,069 postmenopausal women, 50–79 years of age, who were enrolled in the WHI clinical trials or observational study, participated in this study. We estimated dietary cadmium consumption by combining baseline food frequency questionnaire responses with U.S. Food and Drug Administration data on food cadmium content. Participants reported incident invasive breast, endometrial, or ovarian cancer, and WHI centrally adjudicated all cases through August 2009. We applied Cox regression to estimate adjusted hazard ratios (HRs) and 95% CIs for each cancer, comparing quintiles of energy-adjusted dietary cadmium intake.Results: Over an average of 10.5 years, 6,658 invasive breast cancers, 1,198 endometrial cancers, and 735 ovarian cancers were reported. We observed no statistically significant associations between dietary cadmium and risk of any of these cancers after adjustment for potential confounders including total dietary energy intake. Results did not differ in any subgroup of women examined.Conclusions: We found little evidence that dietary cadmium is a risk factor for breast, endometrial, or ovarian cancers in postmenopausal women. Misclassification in dietary cadmium assessment may have attenuated observed associations.Citation: Adams SV, Quraishi SM, Shafer MM, Passarelli MN, Freney EP, Chlebowski RT, Luo J, Meliker JR, Mu L, Neuhouser ML, Newcomb PA. 2014. Dietary cadmium exposure and risk of breast, endometrial, and ovarian cancer in the Women’s Health Initiative. Environ Health Perspect 122:594–600; http://dx.doi.org/10.1289/ehp.1307054