Polychlorinated biphenyls, mercury, and antinuclear antibody positivity, NHANES 2003-2004.

Serum antinuclear antibody positivity (ANA) has been associated with elevated serum polychlorinated biphenyls (PCBs) among residents in PCB-polluted areas; however, associations in general populations have not been reported by congener type or with adjustment for mercury. Cross-sectional data on serum PCBs, total blood mercury, ANA, and potential confounders age, race, body mass index, menopausal status, and dietary eicosapentaenoic acid (EPA) were obtained from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) for males and females aged 12-85. PCB congeners were summed separately for dioxin-like and nondioxin-like PCBs; the former were weighted for toxic equivalent factors. Total PCBs by congener type and mercury were analyzed as both continuous log-transformed variables and as categorical quintiles. Logistic regression models were stratified by sex. There were no associations between nondioxin-like PCBs or mercury and ANA among males or females. Among females (n=114 affected and 518 unaffected), adjusting for potential confounders, the prevalence odds for ANA positivity were significantly elevated per incremental increase in log-transformed dioxin-like PCBs (odds ratio {OR}=1.66; 95% confidence interval {CI}=1.24, 2.23); the highest dioxin-like PCB quintile (>0.00425-0.04339ng/g) was significantly associated with 4.04 (95% CI=2.43, 6.70) greater prevalence odds for ANA positivity relative to the lowest quintile (Ptrend<0.001). We present novel findings of an association between low-level dioxin-like PCBs and ANA among women. No associations were observed between mercury and ANA at mercury levels common to the U.S. population.

Total blood mercury and rubella antibody concentrations in US children aged 6-11 years, NHANES 2003-2004.

BACKGROUND: Children are susceptible to mercury toxicity, and mercury has immunomodulatory effects. Lower folate and B-12, and higher homocysteine may represent susceptibility cofactors. A large proportion of variability in rubella immune response is attributable to environmental factors. OBJECTIVE: This study aimed to evaluate the interaction between total blood mercury (Hg) and nutritional and homocysteine status on rubella virus antibody concentrations. DESIGN: Cross-sectional data on rubella IgG antibody concentrations, Hg, homocysteine, methylmalonic acid (MMA, an indicator of B-12 deficiency), and folate were obtained from 2003-2004 NHANES for children aged 6-11 years with rubella seropositivity (n=690). Linear regression was used to evaluate relationships between log-transformed rubella concentrations and Hg, stratified by sex, MMA ≥, folate<, and homocysteine ≥ sample medians, adjusted for demographic and nutritional cofactors. RESULTS: Hg was significantly positively associated with rubella antibody concentrations (ß=0.24; 95% confidence interval (CI)=0.11, 0.38) in children with higher MMA, lower folate and higher homocysteine (n=110), yet inversely associated among all other children (ß=-0.18; 95% CI=-0.34, -0.03) (n=580). Among the former, estimates (ß) were positive across all Hg quartiles relative to the lowest (Q1) (Hg<0.30 µg/L): Q2: ß=0.23 (-.10, 0.56); Q3: ß=0.35 (0.13, 0.57); Q4: ß=0.53 (0.21, 0.84); P(trend)<0.01. CONCLUSION: Findings are consistent with previously reported associations between Hg and measles antibody concentrations, and highlight the importance of considering dynamics between toxicant exposures, pathogens and host susceptibility.

Performance of cancer cluster Q-statistics for case-control residential histories.

Few investigations of health event clustering have evaluated residential mobility, though causative exposures for chronic diseases such as cancer often occur long before diagnosis. Recently developed Q-statistics incorporate human mobility into disease cluster investigations by quantifying space- and time-dependent nearest neighbor relationships. Using residential histories from two cancer case-control studies, we created simulated clusters to examine Q-statistic performance. Results suggest the intersection of cases with significant clustering over their life course, Q(i), with cases who are constituents of significant local clusters at given times, Q(it), yielded the best performance, which improved with increasing cluster size. Upon comparison, a larger proportion of true positives were detected with Kulldorf's spatial scan method if the time of clustering was provided. We recommend using Q-statistics to identify when and where clustering may have occurred, followed by the scan method to localize the candidate clusters. Future work should investigate the generalizability of these findings.

Mercury and thyroid autoantibodies in U.S. women, NHANES 2007-2008.

Associations between positive thyroid autoantibodies and total blood mercury in women were evaluated using the National Health and Nutrition Examination Survey (NHANES), 2007-2008. Women are at increased risk for autoimmune disorders, mercury exposure has been associated with cellular autoimmunity and mercury accumulates in the thyroid gland. We used multiple logistic regression to evaluate the associations between total bloodmercury and thyroglobulin autoantibody antibody positivity and thyroid peroxidase autoantibody positivity in non-pregnant, non-lactating women aged 20 and older not currently using birth control pills or other hormone therapies, adjusted for demographic factors, menopausal status, nutrient intake and urine iodine (n=2047). Relative to women with the lowest mercury levels (≤0.40 µg/L), women with mercury >1.81 µg/L (upper quintile) showed 2.24 (95% CI=1.22, 4.12) greater odds for thyroglobulin autoantibody positivity (p(trend)=0.032); this relationship was not evident for thyroid peroxidase autoantibody positivity. Results suggest an association between mercury and thyroglobulin autoantibody positivity.

Total blood mercury and serum measles antibodies in US children, NHANES 2003-2004.

BACKGROUND: Environmental toxins, pathogens and host susceptibility cofactors may interact to contribute to disease. In vitro mercury exposure inhibited antiviral cytokines in human cells; however, little is known about the relationship between mercury and viruses in children. Children are susceptible to mercury toxicity; lower vitamin B-12 and folate levels and higher homocysteine levels may represent susceptibility cofactors. This study aimed to evaluate associations between total blood mercury (Hg) and measles antibodies in children, and the influence of these susceptibility cofactors. DESIGN: Cross-sectional data on serum measles antibodies, Hg, homocysteine, methylmalonic acid (MMA, indicator of B-12 deficiency), and folate were obtained from the 2003-2004 NHANES for children aged 6-11 years with measles seropositivity (n=692). We used linear regression to evaluate relationships between measles antibodies and Hg, stratified by sex, MMA ≥, folate <, and homocysteine≥sample medians, adjusted for demographic, nutritional and environmental cofactors. RESULTS: Hg (range: 0.10-19.10µg/L) was inversely associated with measles antibodies (range: 1.00-28.24 units) in non-stratified analysis (n=692), yet positively associated among the subset of boys with higher MMA and lower folate (n=98). Among this subset with higher homocysteine levels (n=61), correlations were positive across all Hg quartiles relative to Q1 (Hg≤0.20µg/L): Q2:ß=6.60 (3.02, 10.19); Q3:ß=8.49 (6.17, 10.81); Q4 (Hg>0.80µg/L):ß=4.90 (2.12, 7.67) (p(trend)=0.077). CONCLUSION: Stratification by susceptibility cofactors revealed opposing directionality for correlations between Hg and measles antibodies, with positive effect estimates at lowest exposures only among boys with higher MMA, lower folate and higher homocysteine levels.

The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20-49 years.

BACKGROUND: Cadmium is a ubiquitous environmental pollutant associated with increased risk of leading causes of mortality and morbidity in women, including breast cancer and osteoporosis. Iron deficiency increases absorption of dietary cadmium, rendering women, who tend to have lower iron stores than men, more susceptible to cadmium uptake. We used body iron, a measure that incorporates both serum ferritin and soluble transferrin receptor, as recommended by the World Health Organization, to evaluate the relationships between iron status and urine and blood cadmium. METHODS: Serum ferritin, soluble transferrin receptor, urine and blood cadmium values in never-smoking, non-pregnant, non-lactating, non-menopausal women aged 20-49 years (n=599) were obtained from the 2003-2008 National Health and Nutrition Examination Surveys. Body iron was calculated from serum ferritin and soluble transferrin receptor, and iron deficiency defined as body iron <0 mg/kg. Robust linear regression was used to evaluate the relationships between body iron and blood and urine cadmium, adjusted for age, race, poverty, body mass index, and parity. RESULTS: Per incremental (mg/kg) increase in body iron, urine cadmium decreased by 0.003 µg/g creatinine and blood cadmium decreased by 0.014 µg/L. Iron deficiency was associated with 0.044 µg/g creatinine greater urine cadmium (95% CI=0.020, 0.069) and 0.162 µg/L greater blood cadmium (95% CI=0.132, 0.193). CONCLUSIONS: Iron deficiency is a risk factor for increased blood and urine cadmium among never-smoking, pre-menopausal, non-pregnant US women, independent of age, race, poverty, body mass index and parity. Expanding programs to detect and correct iron deficiency among non-pregnant women merits consideration as a potential means to reduce the risk of cadmium associated diseases.

Total blood mercury, plasma homocysteine, methylmalonic acid and folate in US children aged 3-5 years, NHANES 1999-2004.

BACKGROUND: Mercury is a known neurotoxicant; however, the relationship between childhood exposures and neurodevelopmental outcomes is uncertain, and may be modified by nutrition-related susceptibilities. In vitro studies found that mercury inhibited methionine synthase, an enzyme that interacts with vitamin B-12 and folate to regenerate the amino acid methionine from homocysteine, and inhibition of methionine synthase diverted homocysteine to cysteine and glutathione synthesis. The relationships between mercury, homocysteine, B-12, and folate have not been examined in children. OBJECTIVE: This study aimed to evaluate associations between Hg and homocysteine in male and female children differentiated by higher and lower methylmalonic acid (MMA, an indicator of vitamin B-12 deficiency) and folate status. DESIGN: Cross-sectional data on total blood mercury (Hg), plasma homocysteine, MMA, and serum folate were obtained from the 1999-2004 National Health and Nutrition Examination Surveys for children aged 3-5 years (n=1005). We used multiple linear regression to evaluate relationships between homocysteine and Hg quartiles, stratified by sex, MMA ≥ and folate < sample medians, adjusted for demographic, anthropometric, and environmental factors. RESULTS: In boys with higher MMA and lower folate (n=135), but not in other children, we observed inverse associations between homocysteine and Hg. Children with Hg >3.49 µmol/L showed 1.14 µmol/L lower homocysteine (p<0.001) relative to the lowest quartile (≤ 0.70 µmol/L) {p-value for trend<0.001}. Compared to other subsamples, this subsample had significantly higher homocysteine levels. CONCLUSION: Hg was inversely correlated with plasma homocysteine in young boys, but not girls, with higher MMA and lower folate. Additional studies are merited to evaluate Hg and amino acid metabolism in susceptible children.

Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002.

Universal hepatitis B vaccination was recommended for U.S. newborns in 1991; however, safety findings are mixed. The association between hepatitis B vaccination of male neonates and parental report of autism diagnosis was determined. This cross-sectional study used weighted probability samples obtained from National Health Interview Survey 1997-2002 data sets. Vaccination status was determined from the vaccination record. Logistic regression was used to estimate the odds for autism diagnosis associated with neonatal hepatitis B vaccination among boys age 3-17 years, born before 1999, adjusted for race, maternal education, and two-parent household. Boys vaccinated as neonates had threefold greater odds for autism diagnosis compared to boys never vaccinated or vaccinated after the first month of life. Non-Hispanic white boys were 64% less likely to have autism diagnosis relative to nonwhite boys. Findings suggest that U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period. Nonwhite boys bore a greater risk.

Environmental cadmium and breast cancer risk.

Breast cancer is the most prevalent women's cancer, with an age-adjusted incidence of 122.9 per 100,000 US women. Cadmium, a ubiquitous carcinogenic pollutant with multiple biological effects, has been reported to be associated with breast cancer in one US regional case-control study. We examined the association of breast cancer with urinary cadmium (UCd), in a case-control sample of women living on Long Island (LI), NY (100 with breast cancer and 98 without), a region with an especially high rate of breast cancer (142.7 per 100,000 in Suffolk County) and in a representative sample of US women (NHANES 1999-2008, 92 with breast cancer and 2,884 without). In a multivariable logistic model, both samples showed a significant trend for increased odds of breast cancer across increasing UCd quartiles (NHANES, p=0.039 and LI, p=0.023). Compared to those in the lowest quartile, LI women in the highest quartile had increased risk for breast cancer (OR=2.69; 95% CI=1.07, 6.78) and US women in the two highest quartiles had increased risk (OR=2.50; 95% CI=1.11, 5.63 and OR=2.22; 95% CI=.89, 5.52, respectively). Further research is warranted on the impact of environmental cadmium on breast cancer risk in specific populations and on identifying the underlying molecular mechanisms.

Blood and urine cadmium, blood pressure, and hypertension: a systematic review and meta-analysis.

BACKGROUND: Cadmium exposure has been inconsistently related to blood pressure. OBJECTIVES: We updated and reevaluated the evidence regarding the relationships of blood cadmium (BCd) and urine cadmium (UCd) with blood pressure (BP) and hypertension (HTN) in nonoccupationally exposed populations. DATA SOURCES AND EXTRACTION: We searched PubMed and Web of Science for articles on BCd or UCd and BP or HTN in nonoccupationally exposed populations and extracted information from studies that provided sufficient data on population, smoking status, exposure, outcomes, and design. DATA SYNTHESIS: Twelve articles met inclusion criteria: eight provided data adequate for comparison, and five reported enough data for meta-analysis. Individual studies reported significant positive associations between BCd and systolic BP (SBP) among nonsmoking women [ß = 3.14 mmHg per 1 µg/L untransformed BCd; 95% confidence interval (CI), 0.14-6.14] and among premenopausal women (ß = 4.83 mmHg per 1 nmol/L log-transformed BCd; 95% CI, 0.17-9.49), and between BCd and diastolic BP (DBP) among women (ß = 1.78 mmHg comparing BCd in the 90th and 10th percentiles; 95% CI, 0.64-2.92) and among premenopausal women (ß = 3.84 mmHg per 1 nmol/L log-transformed BCd; 95% CI, 0.86-6.82). Three meta-analyses, each of three studies, showed positive associations between BCd and SBP (p = 0.006) and DBP (p < 0.001) among women, with minimal heterogeneity (I² = 3%), and a significant inverse association between UCd and HTN among men and women, with substantial heterogeneity (I² = 80%). CONCLUSION: Our results suggest a positive association between BCd and BP among women; the results, however, are inconclusive because of the limited number of representative population-based studies of never-smokers. Associations between UCd and HTN suggest inverse relationships, but inconsistent outcome definitions limit interpretation. We believe a longitudinal study is merited.

Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III.

BACKGROUND: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. OBJECTIVES: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal and perimenopausal women aged 42-60 years. METHODS: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. RESULTS: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; beta=0.45; p< or =0.05; R(2)=0.35) and low BMI (n=408; beta=0.61; p< or =0.01; R(2)=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd (beta=-0.04; p< or =0.05) and FSH (beta=-0.03; p< or =0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p< or =0.01). CONCLUSION: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and both FSH and UCd are associated with bone loss, in US women aged 42-60 years.

Racial disparities in lung cancer mortality in U.S. congressional districts, 1990-2001.

The objective of this study was to detect statistically significant racial disparities in lung cancer mortality at the U.S. congressional district level. We applied absolute disparity statistics to mortality data from the National Center for Health Statistics (NCHS) for 1990-2001, mapped significant lung cancer mortality disparities by race and gender within U.S. congressional districts, and uncovered previously unreported disparities. The disparity statistics comparing black and white females revealed higher mortality rates for black females in the Midwestern U.S., and higher mortality rates for white females in the South-eastern U.S. Our methodology provides a spatial tool for guiding public health cancer control practices to monitor, target and reduce disparities.

Urinary cadmium and osteoporosis in U.S. Women >or= 50 years of age: NHANES 1988-1994 and 1999-2004.

BACKGROUND: Urinary cadmium (U-Cd) has been associated with decreased peripheral bone mineral density (BMD) and osteoporosis. This association, however, has not been confirmed using femoral BMD, the international standard for diagnosing osteoporosis, at levels < 1.0 microg Cd/g creatinine. OBJECTIVES: Our goal was to investigate the statistical association between U-Cd, at levels or= 50 years of age. METHODS: We drew data from the National Health and Nutrition Examination Surveys for 1988-1994 (n = 3,207) and 1999-2004 (n = 1,051). Osteoporosis was indicated by hip BMD cutoffs based on the international standard and self-report of physician diagnosis. We analyzed U-Cd levels for association with osteoporosis using multiple logistic regression. RESULTS: Women >or= 50 years of age with U-Cd levels between 0.50 and 1.00 microg/g creatinine were at 43% greater risk for hip-BMD-defined osteoporosis, relative to those with levels or= 50 years of age.