Overall and Sex-Specific Associations of Serum Lipid-Soluble Micronutrients with Metabolic Dysfunction-Associated Steatotic Liver Disease among Adults in the United States.

This study examined overall and sex-specific associations of serum lipid-soluble micronutrients including α- and γ-tocopherols, 25-hydroxy-vitamin D (25(OH)D), retinol, and six major carotenoids with metabolic dysfunction-associated steatotic lever disease (MASLD) using the 2017-2018 National Health and Nutrition Examination Survey. This analysis included 3956 adults (1991 men, 1965 women) aged ≥ 20 years. Steatotic liver disease was determined through transient elastography examination. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for MASLD associated with micronutrients were estimated using logistic regressions. Higher serum α-tocopherol (highest vs. lowest quartile: OR = 1.53, 95% CI = 1.05-2.22, p = 0.03) and γ-tocopherol (highest vs. lowest quartile: OR = 4.15, 95% CI = 3.00-5.74, p < 0.0001) levels were associated with increased odds of MASLD. Higher serum 25(OH)D levels were associated with reduced odds of MASLD (highest vs. lowest quartile: OR = 0.41, 95% CI = 0.27-0.61, p = 0.0001). Inverse associations with the condition were also observed for carotenoids (α-carotene, ß-carotene, α-cryptoxanthin, ß-cryptoxanthin, combined lutein and zeaxanthin, and lycopene) in the serum (Ps < 0.05). The results were comparable between men and women, except for those on α-tocopherol, for which a positive association was only observed for men (p = 0.01). Our results suggest potential protective associations of serum 25(OH)D and carotenoids with MASLD. The positive associations between tocopherols and MASLD may reflect pathophysiological conditions associated with the condition.

Antiviral Treatment and Response are Associated With Lower Risk of Dementia Among Hepatitis C Virus-Infected Patients.

OBJECTIVE: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated how antiviral therapy impacts the risk of developing dementia among patients with HCV. METHODS: A total of 17,485 HCV patients were followed until incidence of dementia, death, or last follow-up. We used an extended landmark modeling approach, which included time-varying covariates and propensity score justification for treatment selection bias, as well as generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk. RESULTS: After 15 years of follow-up, 342 patients were diagnosed with incident dementia. Patients who achieved sustained virological response (SVR) had significantly decreased risk of dementia compared to untreated patients, with hazard ratios (HRs) of 0.32 (95% CI 0.22-0.46) among patients who received direct-acting antiviral (DAA) treatment and 0.41 (95% CI 0.26-0.60) for interferon-based (IFN) treatment. Risk reduction remained even when patients failed antiviral treatment (HR 0.38, 95% CI 0.38-0.51). Patients with cirrhosis, Black/African American patients, and those without private insurance were at significantly higher risk of dementia. CONCLUSION: Antiviral treatment independently reduced the risk of dementia among HCV patients, regardless of cirrhosis. Our findings support the importance of initiation antiviral therapy in chronic HCV-infected patients.

Association of sleep duration, chronotype, social jetlag, and sleep disturbance with phenotypic age acceleration: A cross-sectional analysis.

OBJECTIVE: Sleep is a critical health-related behavior; research evidence has shown that sleep duration, poor sleep quality and insomnia are associated with aging and relevant age-related diseases. However, the associations between sleep duration, chronotype, sleep disturbance, and biological age have not been comprehensively assessed. This study aimed to examine sleep characteristics with biological age. METHODS: The study included 6534 participants aged 20 years and older from the National Health and Nutrition Examination Survey between 2017 and March 2020. Sleep questionnaires were used to collect information on sleep duration and wake behavior on workdays and workfree days and sleep disturbance. Phenotypic age acceleration (PhenoAgeAccel) was estimated as a biological age measure using 9 blood chemistry biomarkers. RESULTS: Long sleep (>9 hours) and extremely short sleep (≤4 hours) on workdays were positively associated with PhenoAgeAccel, compared with optimal sleep duration (7-8 hours). Similar positive associations with PhenoAgeAccel were observed for sleep duration on workfree days and across the whole week. Both slightly evening and evening chronotypes were associated with faster PhenoAgeAccel compared to morning chronotype. Social jetlag and sleep disturbance were not associated with PhenoAgeAccel, while long corrected social jetlag was associated with faster PhenoAgeAccel. The associations of sleep duration, chronotype, and corrected social jetlag with PhenoAgeAccel appeared stronger among females than among males. CONCLUSIONS: Findings suggest a U-shape relationship between sleep duration and biological aging; slightly evening and evening chronotypes may be risk factors for aging. Further studies are needed to confirm these findings.

Trends in Diet Quality by Race/Ethnicity among Adults in the United States for 2011-2018.

This study aimed to investigate time trends in diet quality and the consumption of major food groups and nutrients by race/ethnicity among adults in the United States. Dietary data from 19,192 adults aged ≥ 20 years from four National Health and Nutrition Survey (NHANES) cycles (2011-2018) were included. The Healthy Eating Index (HEI) 2015 scores (range: 0-100; higher scores indicate better diet quality) and dietary consumption of food groups and nutrients were estimated for each cycle. Linear regression was used to test trends. For the overall population, the estimated overall HEI-2015 scores significantly decreased (p for trend = 0.011). However, decreases were observed in the estimated consumption of added sugars and total carbohydrates, while the estimated consumption of soy products and polyunsaturated fatty acids was significantly increased. A significant decrease in overall HEI-2015 score was observed in the non-Hispanic white group, but not in other racial/ethnic groups. Decreases in added sugar intake were found in the non-Hispanic black and Hispanic groups; sodium intake significantly decreased in the non-Hispanic Asian group. From 2011 to 2018, there was a decrease in estimated overall diet quality in US adults; however, there were improvements in certain nutrients and dietary components. Nevertheless, disparities in diet quality exist among racial/ethnic groups.

Association between magnesium intake and cognition in US older adults: National Health and Nutrition Examination Survey (NHANES) 2011 to 2014.

INTRODUCTION: Identifying nutrition- and modifiable lifestyle-based risk factors for cognitive decline and dementia may contribute future primary prevention strategies. This study aimed to evaluate the associations between magnesium intake and cognition in older adults in the United States. METHODS: Based on the National Health and Nutrition Survey (NHANES) between 2011 and 2014, the study included 2508 participants aged 60 years and older. Linear regression models were used to examine the association of total magnesium intake with cognition. RESULTS: After adjusted demographic and other confounding factors, intakes of energy and total calcium, and serum vitamin D level, higher intake of total magnesium was independently associated with 0.15 higher global cognitive z-score (95% confidence interval, 0.02 to 0.28 for highest vs. lowest quartile, P trend = .037). The positive association of total magnesium intake with global cognition was primarily presented among women, non-Hispanic Whites, and those with sufficient serum vitamin D levels (≥50 nmol/L), although interactions were not significant. There were no clear linear associations for global cognition with serum vitamin D level. DISCUSSIONS: Our findings suggest that high magnesium intake alone may improve cognition in older adults, particularly among non-Hispanic Whites and subjects with sufficient levels of serum vitamin D. Further studies are needed to confirm the findings.

Sleep Duration, Chronotype, and Insomnia and the Risk of Lung Cancer: United Kingdom Biobank Cohort.

BACKGROUND: Relationships between sleep duration, chronotype, insomnia, and lung cancer risk have not been comprehensively examined. Interrelations between sleep traits on the risk of lung cancer have not been assessed. We aimed to examine sleep traits with lung cancer risk. METHODS: Participants were recruited between 2006 and 2010 and followed through November 30, 2020. We included 382,966 participants (3,664 incident lung cancer) in analysis. Cox proportional hazards models estimated HRs and 95% confidence intervals (CI) for associations between sleep duration, chronotype, and insomnia symptoms and lung cancer risk. Joint effects analyses were examined between sleep duration and three traits (chronotype, insomnia, and daytime napping). Nonlinear associations between sleep duration and lung cancer risk were assessed in restricted cubic spline analysis. RESULTS: Longer sleep (>8 hours) was positively associated with lung cancer risk compared with normal sleep duration (7-8 hours; HR = 1.22; 95% CI, 1.10-1.36). Frequent insomnia symptoms increased the risk of lung cancer compared with never/rarely experiencing symptoms (HR = 1.16; 95% CI, 1.05-1.28). Joint effects between sleep duration and chronotype, and sleep duration and insomnia symptoms were observed. In analysis excluding participants reporting shift work at baseline, evening chronotypes ("slight," "definite") were at a greater risk of lung cancer compared with definite morning chronotype (HR = 1.17; 95% CI, 1.06-1.28 and HR = 1.37; 95% CI, 1.21-1.54, respectively). CONCLUSIONS: Sleep traits such as long sleep duration, frequent insomnia symptoms, and definite evening chronotype may be risk factors for lung cancer. Joint effects should be further investigated. IMPACT: Sleep traits may be risk factors of lung cancer.

Factors related to the accurate application of NHSN surveillance definitions for CAUTI and CLABSI in Texas hospitals: A cross-sectional survey.

Previous studies indicate variability in the accurate application of National Healthcare Safety Network surveillance criteria with limited data on possible contributing factors. In this cross-sectional, convenience sampled web-based survey sent to members of Texas infection prevention and control organizations, training, experience, and time spent on surveillance was collected and assessed including 2 case studies. Our results indicate correct identification of catheter-associated urinary tract infection (CAUTI) and central line-associated bloodstream infection (CLABSI) criteria may be associated with 2019 National Healthcare Safety Network training (CAUTI: aOR = 0.17, 95% CI: 0.04, 0.80; CLABSI: aOR = 0.45, 95% CI: 0.045, 4.56) and increased years of infection prevention experience (CAUTI: aOR = 1.35, 95% CI: 0.42, 4.33; CLABSI: aOR = 1.23, 95% CI: 0.24, 6.38). Routinely performing more hours of surveillance may increase accuracy of CLABSI identification, but not CAUTI.

Associations of Dietary Lipid-Soluble Micronutrients with Hepatic Steatosis among Adults in the United States.

Lipid-soluble micronutrients may be beneficial to non-alcoholic fatty liver disease due to their important roles in metabolism and maintaining tissue functions. Utilizing 2017-2018 National Health and Nutrition Examination Survey, this study examined the potential overall and race/ethnicity-specific (black, Hispanic and white) associations of dietary lipid-soluble micronutrients (α-tocopherol, retinol, vitamin D, ß-carotene and total carotenoids) with hepatic steatosis. The analysis included 4376 adults (1037 blacks, 981 Hispanics, 1549 whites) aged ≥20 years who completed the transient elastography examination with dietary data available. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regressions. The age-adjusted prevalence of steatosis was 20.9% for blacks, 34.0% for Hispanics and 28.7% for whites. Overall, dietary α-tocopherol was inversely associated with steatosis (highest vs. lowest quartile: OR = 0.51, 95%CI = 0.35-0.74, Ptrend = 0.0003). The associations remained significant among blacks (highest vs. lowest tertile: OR = 0.45, 95%CI = 0.26-0.77, Ptrend = 0.002) and whites (highest vs. lowest tertile: OR = 0.56, 95%CI = 0.33-0.94, Ptrend = 0.02). Higher α-tocopherol intake was associated with lower odds of steatosis among all (Ptrend = 0.016) and black participants (Ptrend = 0.003) classified as never/rare/occasional alcohol drinkers. There was a trend suggesting higher ß-carotene intake with lower odds of steatosis (Ptrend = 0.01). Our results suggest potential protective effects of dietary vitamin E as α-tocopherol on steatosis particularly among blacks.

Association between acculturation and metabolic syndrome in Hispanic adults mediated by fruits intake.

OBJECTIVES: Hispanic adults in the USA tend to have a disproportionate prevalence of metabolic syndrome (MetS) as compared to other races. DESIGN: We examined whether the association between acculturation and MetS and its components are mediated by the intake of fruit in Hispanics. SETTING: Data from the National Health and Nutrition Examination Surveys 2009-2016 were used in this study. PARTICIPANTS: A total of 2078 Hispanics aged ≥ 20 years were included in this analysis. RESULTS: The mediating role of total fruit intake was assessed using multivariable-adjusted logistic structural equation models with the bootstrapping method by estimating indirect (IE) and direct (DE) effects from acculturation to MetS. High acculturation was associated with increased odds of MetS (adjusted OR = 1·20, 95 % CI 1·04, 1·39), central obesity (OR = 1·24, 95 % CI 1·07, 1·44) and high blood pressure (OR = 1·16, 95 % CI 1·02, 1·32) among Hispanic adults. Total fruits intake partially mediated the associations of acculturation with MetS (ORIE = 1·02, 95 % CI 1·00, 1·03) and central obesity (ORIE = 1·02, 95 % CI 1·00, 1·03), whereas fully mediated the association between acculturation and high blood pressure (ORIE = 1·03, 95 % CI 1·01, 1·06). Moreover, intake of total fruits fully mediated the acculturation-MetS association among Mexican Americans (ORIE = 1·02, 95 % CI 1·00, 1·05). CONCLUSIONS: Our findings suggested that increasing fruit consumption may reduce the impact of high acculturation on MetS development in Hispanic adults. Further studies are needed to confirm these findings.

Association of Magnesium Intake with Liver Fibrosis among Adults in the United States.

Liver fibrosis represents the consequences of chronic liver injury. Individuals with alcoholic or nonalcoholic liver diseases are at high risk of magnesium deficiency. This study aimed to evaluate the association between magnesium and calcium intakes and significant liver fibrosis, and whether the associations differ by alcohol drinking status. Based on the National Health and Nutrition Examination Survey (NHANES) 2017-2018, the study included 4166 participants aged >18 years who completed the transient elastography examination and had data available on magnesium intake. The median liver stiffness of 8.2 kPa was used to identify subjects with significant fibrosis (≥F2). The age-adjusted prevalence of significant fibrosis was 12.81%. Overall total magnesium intake was marginally associated with reduced odds of significant fibrosis (p trend = 0.14). The inverse association of total magnesium intake with significant fibrosis was primarily presented among those who had daily calcium intake <1200 mg. There were no clear associations for significant fibrosis with calcium intake. Findings suggest that high total magnesium alone may reduce risk of significant fibrosis. Further studies are needed to confirm these findings.

Association of magnesium intake and vitamin D status with cognitive function in older adults: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014.

PURPOSE: Reduced cognitive function associated with aging has gained increasing attention as the US population ages. Magnesium plays a critical role in vitamin D biosynthesis and metabolism; and deficiencies in magnesium and vitamin D show associations with poor cognition. However, no study has examined their interaction. This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, indicating vitamin D status, with cognition, and interaction between these nutrients in older adults. METHODS: Based on the National Health and Nutrition Survey (NHANES) 2011-2014, the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test (DSST) and had data available on serum 25(OH)D and magnesium intake. Cognitive impairment was defined as a DSST score lower than the lowest quartile. Serum 25(OH)D concentrations were measured by HPLC-tandem mass spectrometry. RESULTS: Higher total magnesium intake was independently associated with higher DSST scores (highest quartile vs lowest: ß = 4.34, 95% CI 1.14-7.54). The association of total magnesium intake with high DSST score was primarily observed among women, non-Hispanic whites, physically active participants and those with sufficient vitamin D status, although the interactions were not significant. The odds of cognitive impairment was reduced with increasing intake of total magnesium (p trend < 0.01) and higher level of serum 25(OH)D (p trend = 0.05). CONCLUSIONS: Findings suggest that high magnesium intake alone may improve cognitive function in older adults, and the association may be stronger among subjects with sufficient vitamin D status. Further studies are needed to confirm these findings.

Association of serum levels of antioxidant micronutrients with mortality in US adults: National Health and Nutrition Examination Survey 1999-2002.

OBJECTIVE: To examine associations between serum antioxidant levels and mortality (all-cause, cancer and CVD) among US adults. DESIGN: We examined the risk of death from all-cause and cause-specific mortality associated with serum antioxidant (vitamin E and carotenoids) and vitamin A levels using Cox regression models to estimate hazards ratios (HR) and 95 % CI. SETTING: The National Health and Nutrition Examination Survey (NHANES) 1999-2002 was followed up through 31 December 2015. PARTICIPANTS: The NHANES 1999-2002 cohort included 8758 participants aged ≥ 20 years. Serum carotenoid levels were only assessed for the 1999-2000 cycle. Therefore, sample size for each assessed antioxidant ranged from 4633 to 8758. RESULTS: Serum vitamin E level was positively associated with all-cause mortality (HR = 1·22, 95 % CI 1·04, 1·43, highest v. lowest quartile). No other antioxidants were associated with mortality in overall analysis. In race/ethnicity-specific analyses, high vitamin E and α-tocopherol levels were associated with increased risk of all-cause mortality among non-Hispanic Whites. Among non-Hispanic Blacks, serum α-tocopherol level was associated with decreased risk of cancer mortality (HR = 0·30, 95 % CI 0·12, 0·75, third v. first quartile) and total carotenoid levels with reduced risk of CVD mortality (HR = 0·26; 95 % CI 0·07, 0·97, second v. lowest quartile). Hispanics with high ß-carotene levels had reduced risk of CVD mortality. CONCLUSIONS: Serum antioxidant levels may be related to mortality; these associations may differ by race/ethnicity and appeared to be non-linear for all-cause and cause-specific mortality. Further studies are needed to confirm our results.

Understanding the Interplay Between Health Disparities and Epigenomics.

Social epigenomics has emerged as an integrative field of research focused on identification of socio-environmental factors, their influence on human biology through epigenomic modifications, and how they contribute to current health disparities. Several health disparities studies have been published using genetic-based approaches; however, increasing accessibility and affordability of molecular technologies have allowed for an in-depth investigation of the influence of external factors on epigenetic modifications (e.g., DNA methylation, micro-RNA expression). Currently, research is focused on epigenetic changes in response to environment, as well as targeted epigenetic therapies and environmental/social strategies for potentially minimizing certain health disparities. Here, we will review recent findings in this field pertaining to conditions and diseases over life span encompassing prenatal to adult stages.

Association of Home Food Availability with Prediabetes and Diabetes among Adults in the United States.

This study examined associations of home food availabilities with prediabetes and diabetes among 8929 adults (20-70 years) participating in 2007-2010 National Health and Nutrition Examination Surveys. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. Relative to non-diabetic participants (individuals without diabetes or prediabetes), prediabetes participants were associated with lower availabilities of green vegetables (OR = 0.82; 95% CI = 0.73-0.91; p = 0.0006) and fat-free/low-fat milk (OR = 0.80, 95% CI = 0.65-0.89; p = 0.001) and higher sugary drink availability (OR = 1.24, 95% CI = 1.04-1.48; p = 0.02), adjusting for age, sex, and ethnicity (Model 1). The associations remained significant for vegetables (p = 0.005) and fat-free/low-fat milk (p = 0.02) adjusting for additional confounders (body mass index, education, Model 2). Adjusting for dietary components did not change the above results (in model 2) significantly. Participants with high healthy food availability scores had approximately 31% reduction (p = 0.003) in odds of prediabetes compared to those with low scores in Model 1. No associations were detected for diabetes except for fat-free/low-fat milk availability, for which an inverse association was observed in Model 1 (OR = 0.80, 95% CI = 0.65-0.99; p = 0.04). The results show prediabetes participants had lower availability of healthy foods and higher availability of unhealthy foods, suggesting the need to improve healthy food availability at home for this population.

Trends in Magnesium Intake among Hispanic Adults, the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

This study aimed at examining trends in magnesium intake among U.S. Hispanic adults stratified by gender, Hispanic origins, age, and poverty income ratio (PIR) level. Data on 9304 Hispanic adults aged ≥20 years from eight National Health and Nutrition Examination Survey (NHANES) cycles (1999-2014) were included in this study. For each cycle, survey-weighted mean dietary and total magnesium intakes were estimated. The prevalence of dietary and total magnesium intake below the Recommended Dietary Allowance (RDA) was further estimated stratified by gender and age groups. Linear regression was used to test trend. Over the survey cycles, both dietary and total magnesium intakes were significantly increased among Hispanic adults. In the study period, magnesium intake tended to be lower in females, adults in other Hispanic-origin group, those aged ≥65 years old, and those with a PIR <1.0. The prevalence of magnesium intake inadequacy decreased among Hispanic adults; however, more than 70% of Hispanic males and females continued to have magnesium intake below the RDA in 2013-2014. From 1999/2000 to 2013/2014, despite several improvements in magnesium intake having been identified, additional findings showed insufficient intake in Hispanic males and females, suggesting the need to improve magnesium intake through diet and dietary supplementation for U.S. Hispanics.

Comparison of Dietary Micronutrient Intakes by Body Weight Status among Mexican-American and Non-Hispanic Black Women Aged 19-39 Years: An Analysis of NHANES 2003-2014.

The objective of the current study was to examine micronutrient intake from foods in women of childbearing age and to better understand potential nutritional problems varied by body weight status in minority women. A sample of women aged 19-39 years from the National Health and Nutrition Examination Surveys (NHANES) 2003-2014 was analyzed. Dietary intakes of 13 micronutrients were estimated using the National Cancer Institute method. Mexican-American and non-Hispanic Black women were categorized into normal/under-weight, overweight, or obese groups according to their body mass index (BMI). Mexican-American and non-Hispanic Black women had lower dietary intakes for vitamins A, B2, B6, B12, and D, folate, calcium, and magnesium than non-Hispanic Whites. Among Mexican-Americans, obese women had the lowest dietary intake of vitamins A, B2, C and D. Obese non-Hispanic Black women had significantly lower dietary intakes of iron and zinc than their normal/under-weight counterparts. Comparable percentages (>30%) of Mexican-American and non-Hispanic Black women had dietary intake less than the Estimated Average Requirements (EARs) for several key nutrients including vitamin A, C and D, folate, calcium and magnesium, and the percentages varied by body weight status. These results indicate micronutrient inadequacies persist among and within racial/ethnic and body weight groups.

Active and secondhand smoke exposure throughout life and DNA methylation in breast tumors.

PURPOSE: Tobacco smoke exposure has been associated with altered DNA methylation. However, there is a paucity of information regarding tobacco smoke exposure and DNA methylation of breast tumors. METHODS: We conducted a case-only analysis using breast tumor tissue from 493 postmenopausal and 225 premenopausal cases in the Western New York Exposures and Breast Cancer (WEB) study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A, CCND2, BRCA1, FHIT, and SYK) was measured with pyrosequencing. Participants reported their secondhand smoke (SHS) and active smoking exposure for seven time periods. Unconditional logistic regression was used to estimate odds ratios (OR) of having methylation higher than the median. RESULTS: SHS exposure was associated with tumor DNA methylation among postmenopausal but not premenopausal women. Active smoking at certain ages was associated with increased methylation of GSTP1, FHIT, and CDKN2A and decreased methylation of SCGB3A1 and BRCA1 among both pre- and postmenopausal women. CONCLUSION: Exposure to tobacco smoke may contribute to breast carcinogenesis via alterations in DNA methylation. Further studies in a larger panel of genes are warranted.

No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe.

Alterations in global DNA methylation have been suggested to play an important role in cancer development. We evaluated the association of global DNA methylation in peripheral blood with the risk of lung cancer in nonsmoking women from six countries in Central and Eastern Europe. This multicenter case-control study included primary, incident lung cancer cases diagnosed from 1998 to 2001 and controls frequency-matched for geographic area, sex, and age. Global methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases and 181 nonsmoking female controls using the luminometric methylation assay (LUMA). Unconditional logistic regression models were used to estimate associations between DNA methylation in the blood and the risk of lung cancer. LUMA methylation level was not associated with the risk of lung cancer in nonsmoking women. Associations were not significantly different according to different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke exposure status. In our study of nonsmoking women, the LUMA methylation level in peripheral blood was not associated with the risk of lung cancer. Our findings do not support an association of global blood DNA methylation with the risk of lung cancer in nonsmoking women.

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors.

BACKGROUND: We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. METHODS: We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. RESULTS: Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23-0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03-3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05-5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26-0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). CONCLUSIONS: We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

BACKGROUND: Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women's Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial. METHODS: The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50-79 years, recruited at 40U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models. RESULTS: After 11 years' cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71-1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment (p=0.04 for interaction). CONCLUSIONS: Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers.