Esther García-Esquinas

Cadmium Exposure and Cancer Mortality in a Prospective Cohort: The Strong Heart Study

Background: Cadmium (Cd) is a toxic metal classified as a human carcinogen by the International Agency for Research on Cancer. Objective: We evaluated the association of long-term Cd exposure, as measured in urine, with cancer mortality in American Indians from Arizona, Oklahoma, and North and South Dakota who participated in the Strong Heart Study during 1989–1991. Methods: The Strong Heart Study was a prospective cohort study of 3,792 men and women 45–74 years of age who were followed for up to 20 years. Baseline urinary Cd (U-Cd) was measured using inductively coupled plasma mass spectrometry. We assessed cancer events by annual mortality surveillance. Results: The median (interquintile range) U-Cd concentration was 0.93 (0.55, 1.63) μg/g creatinine. After adjusting for sex, age, smoking status, cigarette pack-years, and body mass index, the adjusted hazard ratios (HRs) comparing the 80th versus the 20th percentiles of U-Cd were 1.30 (95% CI: 1.09, 1.55) for total cancer, 2.27 (95% CI: 1.58, 3.27) for lung cancer, and 2.40 (95% CI: 1.39, 4.17) for pancreatic cancer mortality. For all smoking-related cancers combined, the corresponding HR was 1.56 (95% CI: 1.24, 1.96). Cd was not significantly associated with liver, esophagus and stomach, colon and rectum, breast, prostate, kidney, or lymphatic and hematopoietic cancer mortality. On the basis of mediation analysis, we estimated that the percentage of lung cancer deaths due to tobacco smoking that could be attributed to Cd exposure was 9.0% (95% CI: 2.8, 21.8). Conclusions: Low-to-moderate Cd exposure was prospectively associated with total cancer mortality and with mortality from cancers of the lung and pancreas. The implementation of population-based preventive measures to decrease Cd exposure could contribute to reducing the burden of cancer. Citation: García-Esquinas E, Pollan M, Tellez-Plaza M, Francesconi KA, Goessler W, Guallar E, Umans JG, Yeh J, Best LG, Navas-Acien A. 2014. Cadmium exposure and cancer mortality in a prospective cohort: the Strong Heart Study. Environ Health Perspect 122:363–370; http://dx.doi.org/10.1289/ehp.1306587

Arsenic Exposure and Cancer Mortality in a US-Based Prospective Cohort: The Strong Heart Study

Background: Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. Prospective studies on carcinogenic effects at low–moderate arsenic levels are lacking. Methods: We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians, 45 to 74 years of age, from Arizona, Oklahoma, and North/South Dakota who participated in the Strong Heart Study from 1989 to 1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, and 40 lymphatic/hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate, and kidney cancers. Results: Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8–15.6) μg/g creatinine. The adjusted HRs [95% confidence interval (CI)] comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92–1.41) for overall cancer, 1.56 (1.02–2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28–8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09–5.58) for pancreatic cancer, and 0.46 (0.22–0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast. Conclusions: Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate, and pancreas. Impact: These findings support the role of low–moderate arsenic exposure in development of lung, prostate, and pancreas cancer and can inform arsenic risk assessment. Cancer Epidemiol Biomarkers Prev; 22(11); 1944–53. ©2013 AACR.

Secondhand Tobacco Smoke: A Source of Lead Exposure in US Children and Adolescents

OBJECTIVES We evaluated the relationship between secondhand tobacco smoke (SHS) exposure and blood lead levels in US children and adolescents. METHODS We analyzed data from 6830 participants aged 3-19 years in the National Health and Nutrition Examination Survey (1999-2004) who were not active smokers and for whom SHS exposure information and blood lead measurements were available. RESULTS After multivariable adjustment, participants in the highest quartile of serum cotinine (≥ 0.44 μg/L) had 28% (95% confidence interval = 21%, 36%) higher blood lead levels than had those in the lowest quartile (< 0.03 μg/L). Similarly, blood lead levels were 14% and 24% higher in children who lived with 1 or with 2 or more smokers, respectively, than they were in children living with no smokers. Among participants for whom lead dust information was available, the associations between SHS and blood lead levels were similar before and after adjustment for lead dust concentrations. CONCLUSIONS SHS may contribute to increased blood lead levels in US children. Lead dust does not appear to mediate this association, suggesting inhalation as a major pathway of exposure. Eliminating SHS exposure could reduce lead exposure in children.

Gastric cancer mortality trends in Spain, 1976-2005, differences by autonomous region and sex

BackgroundGastric cancer is the second leading cause of oncologic death worldwide. One of the most noteworthy characteristics of this tumors epidemiology is the marked decline reported in its incidence and mortality in almost every part of the globe in recent decades. This study sought to describe gastric cancer mortality time trends in Spains regions for both sexes.MethodsMortality data for the period 1976 through 2005 were obtained from the Spanish National Statistics Institute. Cases were identified using the International Classification of Diseases 9th and 10th revision (codes 151 and C16, respectively). Crude and standardized mortality rates were calculated by geographic area, sex, and five-year period. Joinpoint regression analyses were performed to ascertain whether changes in gastric cancer mortality trends had occurred, and to estimate the annual percent change by sex and geographic area.ResultsGastric cancer mortality decreased across the study period, with the downward trend being most pronounced in women and in certain regions situated in the interior and north of mainland Spain. Across the study period, there was an overall decrease of 2.90% per annum among men and 3.65% per annum among women. Generally, regions in which the rate of decline was sharpest were those that had initially registered the highest rates. However, the rate of decline was not constant throughout the study period: joinpoint analysis detected a shift in trend for both sexes in the early 1980s.ConclusionGastric cancer mortality displayed in both sexes a downward trend during the study period, both nationally and regionally. The different trend in rates in the respective geographic areas translated as greater regional homogeneity in gastric cancer mortality by the end of the study period. In contrast, rates in women fell more than did those in men. The increasing differences between the sexes could indicate that some risk factors may be modifying the sex-specific pattern of this tumor.

Kidney function and tobacco smoke exposure in US adolescents.

BACKGROUND AND OBJECTIVE: Active smoking and secondhand smoke (SHS) are known risk factors for kidney disease in adults. We evaluated the association between exposure to active smoking or SHS and kidney function in US adolescents. METHODS: This is a cross-sectional study in 7516 adolescents aged 12–17 who participated in NHANES 1999–2010 and had serum creatinine and cotinine measures. Active smoking was defined as self-reported smoking or serum cotinine concentrations >10 ng/mL. SHS was defined as nonactive smokers who self-reported living with ≥1 smokers or serum cotinine concentrations ≥ 0.05 ng/mL. Kidney function was determined by using the chronic kidney disease in children estimated glomerular filtration rate (eGFR) equation. RESULTS: Median (interquartile range) eGFR and serum cotinine concentrations were 96.8 (85.4–109.0) mL/minute per 1.73 m2 and 0.07 (0.03–0.59) ng/mL, respectively. After multivariable adjustment, eGFR decreased 1.1 mL/minute per 1.73 m2 (95% confidence interval [CI]: −1.8 to −0.3) per interquartile range increase in serum cotinine concentrations. The mean (95%CI) difference in eGFR for serum cotinine tertiles 1, 2, and 3 among children exposed to SHS compared to unexposed were −0.4 (−1.9 to 1.2), −0.9 (−2.7 to 0.9), and −2.2 (−4.0 to −0.4) mL/minute per 1.73 m2, respectively (P = .03). The corresponding values among tertiles of active smokers compared to unexposed were 0.2 (−2.2 to 2.6), −1.9 (−3.8 to 0.0), and −2.6 (−4.6 to −0.6) mL/minute per 1.73 m2 (P = .01). CONCLUSIONS: Tobacco smoke exposure was associated with decreased eGFR in US adolescents, supporting the possibility that tobacco smoke effects on kidney function begin in childhood.

Association of lead and cadmium exposure with frailty in US older adults.

BACKGROUND Environmental lead and cadmium exposure is associated with higher risk of several age-related chronic diseases, including cardiovascular disease, chronic kidney disease and osteoporosis. These diseases may lead to frailty, a geriatric syndrome characterized by diminished physiologic reserve in multiple systems with decreased ability to cope with acute stressors. However, no previous study has evaluated the association between lead or cadmium exposure and frailty. METHODS Cross-sectional study among individuals aged ≥ 60 years who participated in the third U.S. National Health and Nutrition Examination Survey and had either blood lead (N=5272) or urine cadmium (N=4887) determinations. Frailty was ascertained with a slight modification of the Fried criteria, so that individuals meeting ≥ 3 of 5 pre-defined criteria (exhaustion, low body weight, low physical activity, weakness and slow walking speed), were considered as frail. The association between lead and cadmium with frailty was evaluated using logistic regression with adjustment for relevant confounders. RESULTS Median (intertertile range) concentrations of blood lead and urine cadmium were 3.9 µg/dl (2.9-4.9) and 0.62 µg/l (0.41-0.91), respectively. The prevalence of frailty was 7.1%. The adjusted odds ratios (95% confidence interval) of frailty comparing the second and third to the lowest tertile of blood lead were, respectively, 1.40 (0.96-2.04) and 1.75 (1.33-2.31). Lead concentrations were also associated with the frequency of exhaustion, weakness and slowness. The corresponding odds ratios (95% confidence interval) for cadmium were, respectively, 0.97 (0.68-1.39) and 1.55 (1.03-2.32), but this association did not hold after excluding participants with reduced glomerular filtration rate: 0.70 (0.43-1.14) and 1.09 (0.56-2.11), respectively. CONCLUSIONS In the US older adult population, blood lead but not urine cadmium concentrations showed a direct dose-response relationship with frailty. These findings support that lead exposure increases frailty in older adults.

Allergic Sensitization, Rhinitis and Tobacco Smoke Exposure in US Adults.

Introduction Tobacco exposure has been linked with sinonasal pathology and may be associated with allergic sensitization. This study evaluates the association between exposure to active smoking or secondhand smoke (SHS) and the prevalence of rhinitis and allergic sensitization in the US adult population. Methods Cross-sectional study in 4,339 adults aged 20–85 in the National Health and Nutrition Examination Survey, 2005–2006. Never smoking was defined as reported lifetime smoking less than 100 cigarettes and serum cotinine levels <10ng/ml, while active smoking was defined as self-reported smoking or serum cotinine concentrations > 10 ng/mL. Self-reported rhinitis was based on symptoms during the past 12 months, and allergen sensitization was defined as a positive response to any of the 19 specific IgE antigens tested. Results Almost half of the population (43%) had detectable levels of IgE specific to at least one inhaled allergen and 32% reported a history of rhinitis. After multivariate adjustment, there was a statistically significant association between the highest serum cotinine tertile and rhinitis in active smokers (OR 1.42; 95%CI 1.00–2.00). The association between active smoking and rhinitis was stronger in individuals without allergic sensitization (OR 2.47; 95%CI 1.44–4.23). There was a statistically significant association between increasing cotinine tertiles and decreased odds of inhaled allergen sensitization (p-trend <.01). Conclusion Tobacco smoke exposure was associated with increased prevalence of rhinitis symptoms, but not with allergic sensitization. The results indicate that the relationship between tobacco smoke exposure and sinonasal pathology in adults may be independent of allergic sensitization.

Short-term variability and nocturnal decline in ambulatory blood pressure in normotension, white-coat hypertension, masked hypertension and sustained hypertension: A population-based study of older individuals in Spain

Blood pressure (BP) variability and nocturnal decline in blood pressure are associated with cardiovascular outcomes. However, little is known about whether these indexes are associated with white-coat and masked hypertension. We performed a cross-sectional analysis of 1047 community-dwelling individuals aged ⩾60 years in Spain in 2012. Three observer-measured home BPs and 24-h ambulatory blood pressure monitoring (ABPM) were performed under standardized conditions. BP variability was defined as BP s.d. and coefficient of variation. Differences in BP variability and nocturnal BP decrease between groups were adjusted for sociodemographic and clinical covariates using generalized linear models. Of the cohort, 21.7% had white-coat hypertension, 7.0% had masked hypertension, 21.4% had sustained hypertension, and 49.9% were normotensive. Twenty-four hour, daytime and night-time systolic BP s.d. and coefficients of variation were significantly higher in subjects with white-coat hypertension than those with normotension (P<0.05) and were similar to subjects with sustained hypertension. In untreated subjects, 24-h but not daytime or night-time BP variability indexes were significantly higher in subjects with white-coat hypertension than in those with normotension (P<0.05). Percentage decrease in nocturnal systolic and diastolic BP was greatest in the white-coat hypertension group and lowest in the masked hypertension group in all patients and untreated patients (P<0.05). Lack of nocturnal decline in systolic blood pressure was observed in 70.2% of subjects with normotension, 57.8% of subjects with white-coat hypertension, 78.1% of subjects with masked hypertension, and 72.2% of subjects with sustained hypertension (P<0.001). In conclusion, 24-h BP variability was higher in subjects with white-coat hypertension and blunted nocturnal BP decrease was observed more frequently in subjects with masked hypertension. These findings may help to explain the reports of increased cardiovascular risk in patients with white-coat hypertension and poor prognosis in those with masked hypertension, highlighting the importance of ABPM.

Tobacco Smoke Exposure and Eustachian Tube Disorders in US Children and Adolescents

Objectives To describe the association between active, environmental tobacco smoke (ETS) exposure and the prevalence of eustachian tube dysfunction (ETD) in the U.S. pediatric population. Study Design Cross-sectional. Setting U.S. representative demographic and audiometric data from the National Health and Nutrition Examination Survey (NHANES);2005–2010. Subjects and Methods The study consisted of 2,977 children aged 12–19 years. ETD was defined as middle ear pressure <100mm H20. ETS was defined as non-active smoking in individuals with serum cotinine over the limit of detection (≥0.015 ng/mL) and <10 ng/mL(N = 1559). Results The prevalence of ETD was 6.1%. After multivariate adjustment for age, sex, body mass index, education level, ethnicity, or having a cold, sinus problem or earache during the last 24 hours, compared to unexposed children, the odds ratios (95% confidence interval) of ETD for those exposed to ETS ages 12–15 in the first, second and third tertile of cotinine concentrations were, respectively, 1.38 (0.53–3.60), 0.99 (0.53–3.60) and 2.67 (1.12–6.34). Similarly, the odds ratios (95% confidence interval) of ETD for those exposed to ETS ages 16–19 in the first, second and third tertile of cotinine concentrations were, respectively, 1.28 (0.48–3.41), 0.99 (0.40–2.48) and 2.86 (1.19–6.88). Conclusion These data suggest that children and adolescents exposed to high concentrations of ETS may have an increased prevalence of ETD.

Lead exposure and increased food allergic sensitization in U.S. children and adults

Whether blood lead levels are associated with sensitization to food allergens in adults and children is unclear. Prior studies have shown that exposure to lead is associated with atopic sensitization and modulation of several cytokines (eg, interleukin [IL]‐12, IL‐10, interferon [IFN]‐γ, and IL‐4 production) and with T‐cell dysregulation and bias toward T helper 2 (Th2) activity. The objective of this work was to assess whether exposure to lead is independently associated with allergic symptoms and sensitizations in a large nationally representative sample of children and adults.