Healthy eating patterns and epigenetic measures of biological age.

BACKGROUND: Healthy eating is associated with lower risks of disease and mortality, but the mechanisms underlying these associations are unclear. Age is strongly related to health outcomes, and biological age can be estimated using the blood methylome. OBJECTIVES: To determine whether healthy eating patterns are associated with methylation-based measures of biological age. METHODS: Among women in the Sister Study, we calculated scores on 4 recommendation-based healthy eating indexes [Dietary Approaches to Stop Hypertension diet, Healthy Eating Index-2015, Alternative Healthy Eating Index (aHEI-2010), and the Alternative Mediterranean diet] using a validated 110-item Block FFQ completed at enrollment. Genome-wide DNA methylation data were generated using the HumanMethylation450 BeadChip on whole blood samples collected at enrollment from a case-cohort sample of 2694 women and were used to calculate 4 measures of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, and GrimAgeAccel). Linear regression models, adjusted for covariates and cohort sampling weights, were used to examine cross-sectional associations between eating patterns and measures of biological age. RESULTS: All 4 healthy eating indexes had inverse associations with epigenetic age acceleration, most notably with PhenoAgeAccel and GrimAgeAccel. Of these, the strongest associations were for aHEI-2010 [per 1-SD increase in diet quality, PhenoAgeAccel ß = -0.5 y (95% CI: -0.8 to -0.2 y) and GrimAgeAccel ß = -0.4 y (95% CI: -0.6 to -0.3 y)]. Although effect modification was not observed for most lifestyle factors, in analyses stratified by physical activity, the benefits of a healthy diet on epigenetic age acceleration were more pronounced among women who did not meet physical activity guidelines (reporting <2.5 h/wk of exercise). CONCLUSIONS: Higher diet quality is inversely associated with methylation-based measures of biological age. Improving diet could have the most benefits in lowering biological age among women with lower levels of physical activity. This trial was registered at clinicaltrials.gov as NCT00047970.

Higher diet-dependent acid load is associated with risk of breast cancer: Findings from the sister study.

Dietary factors that contribute to chronic low-grade metabolic acidosis have been linked to breast cancer risk, but to date no epidemiologic study has examined diet-dependent acid load and breast cancer. We used data from 43,570 Sister Study participants who completed a validated food frequency questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. The Potential Renal Acid Load (PRAL) score was used to estimate diet-dependent acid load. Higher scores reflect greater consumption of protein and phosphorus, and lower consumption of potassium, calcium and magnesium. The association between PRAL and breast cancer was evaluated using multivariable Cox proportional hazards regression. We identified 1,614 invasive breast cancers diagnosed at least 1 year after enrollment (mean follow-up, 7.6 years). The highest PRAL quartile, reflecting greater acid-forming potential, was associated with increased risk of breast cancer (HRhighest vs. lowest quartile : 1.21 [95% CI, 1.04-1.41], ptrend = 0.04). The association was more pronounced for estrogen receptor (ER)-negative (HRhighest vs. lowest quartile : 1.67 [95% CI, 1.07-2.61], ptrend = 0.03) and triple-negative breast cancer (HRhighest vs. lowest quartile : 2.20 [95% CI, 1.23-3.95], ptrend = 0.02). Negative PRAL scores, representing consumption of alkaline diets, were associated with decreased risk of ER-negative and triple-negative breast cancer, compared to a PRAL score of 0 representing neutral pH. Higher diet-dependent acid load may be a risk factor for breast cancer while alkaline diets may be protective. Since PRAL scores are positively correlated with meat consumption and negatively correlated with fruit and vegetable intake, results also suggest that diets high in fruits and vegetables and low in meat may be protective against hormone receptor negative breast cancer.

A cohort study of in utero polychlorinated biphenyl (PCB) exposures in relation to secondary sex ratio.

BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals that persist in the environment and in human fatty tissue. PCBs are related to a class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro-dibenzodioxin), which has been implicated as a cause of altered sex ratio, especially in relation to paternal exposures. METHODS: In the 1960's, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20 degrees C. For this study, samples were thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex ratio, or sex ratio at birth, was evaluated as a function of maternal serum concentrations using log-binomial and logistic regression, controlling for hormonally active medications taken during pregnancy. RESULTS: The relative risk of a male birth decreased by 33% comparing women at the 90th percentile of total PCBs with women at the 10th percentile (RR = 0.67; 95% CI, 0.48-0.94; p = 0.02), or by approximately 7% for each 1 mug/L increase in total PCB concentration. Although some congener-specific associations with sex ratio were only marginally statistically significant, all nine PCB congeners with < 30% of samples below the LOQ showed the same direction of association, an improbable finding under the null hypothesis. CONCLUSION: Maternal exposure to PCBs may be detrimental to the success of male sperm or to the survival of male embryos. Findings could be due to contaminants, metabolites or PCBs themselves.

Coal home heating and environmental tobacco smoke in relation to lower respiratory illness in Czech children, from birth to 3 years of age.

OBJECTIVE: The objective of this study was to evaluate how indoor pollution from tobacco and home heating may adversely affect respiratory health in young children. DESIGN: A birth cohort was followed longitudinally for 3 years to determine incidence of lower respiratory illness (LRI). PARTICIPANTS: A total of 452 children born 1994-1996 in two districts in the Czech Republic participated. EVALUATIONS: Indoor combustion exposures were home heating and cooking fuel, mother's smoking during pregnancy, and other adult smokers in the household. Diagnoses of LRI (primarily acute bronchitis) from birth to 3 years of age were abstracted from pediatric records. Questionnaires completed at delivery and at 3-year follow-up provided covariate information. LRI incidence rates were modeled with generalized linear models adjusting for repeated measures and for numerous potential confounders. RESULTS: LRI diagnoses occurred more frequently in children from homes heated by coal [vs. other energy sources or distant furnaces ; rate ratio (RR) = 1.45 ; 95% confidence interval (CI) , 1.07-1.97]. Maternal prenatal smoking and other adult smokers also increased LRI rates (respectively: RR = 1.48 ; 95% CI, 1.10-2.01 ; and RR = 1.29 ; 95% CI, 1.01-1.65) . Cooking fuels (primarily electricity, natural gas, or propane) were not associated with LRI incidence. For children never breast-fed, coal home heating and mother's smoking conferred substantially greater risks: RR = 2.77 (95% CI, 1.45-5.27) and RR = 2.52 (95% CI, 1.31-4.85) , respectively. CONCLUSIONS: Maternal smoking and coal home heating increased risk for LRI in the first 3 years of life, particularly in children not breast-fed. RELEVANCE: Few studies have described effects of coal heating fuel on children's health in a Western country. Breast-feeding may attenuate adverse effects of prenatal and childhood exposures to combustion products.

In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth.

BACKGROUND: Polychlorinated biphenyls (PCBs) are industrial chemicals that were used widely for approximately 50 years. Now banned, they are still ubiquitous because of their persistence in the environment, the food chain, and human fatty tissue. High in utero exposures cause developmental deficits accompanied by growth retardation. Studies examining intrauterine growth at lower exposures have been inconsistent, with most such investigations having relied on surrogate exposure indicators such as consumption of fish from contaminated bodies of water. METHODS: In the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20 degrees C. At 5 years of age, detailed anthropometric measurements were made on children born in the years 1964-1967. We measured PCBs in specimens from 399 mothers using gas chromatography/electron capture detection. We conducted multiple linear regression to examine the relationship between these organochlorine concentrations and both intrauterine and 5-year growth, with adjustment for medical, lifestyle, sociodemographic, and specimen characteristics. RESULTS: In male infants, higher total in utero PCB exposure was associated with reduced birth weight, head circumference, and weight-for-gestational age. An increase from the 10th to 90th percentile in total PCBs was related to 290 g lower birth weight, a 0.7-cm decrease in head circumference, and for weight for gestational age, a reduction in z-score of 0.6. In girls, smaller head circumference and shorter gestations were observed. In contrast, prenatal PCBs were associated with greater growth in 5-year-old girls, with no apparent effect in 5-year-old boys. CONCLUSIONS: Maternally mediated exposure to PCBs may be detrimental to fetal growth, particularly in boys. These effects apparently are not persistent. Interpretation of greater childhood growth of girls is unclear.

Determinants of serum polychlorinated biphenyls and organochlorine pesticides measured in women from the child health and development study cohort, 1963-1967.

We examined predictors of organochlorine concentrations in serum specimens from women who were pregnant in the 1960s and participated in the Child Health and Development Study in the San Francisco Bay Area of California. That study enrolled pregnant women at the Kaiser-Permanente Medical Facilities, conducted interviews, and drew blood specimens; these specimens were centrifuged and the resulting serum specimens were frozen and placed in long-term storage. For the current investigation, organochlorines were measured by dual-column GC-electron capture detection in specimens collected in 1963-1967 from 399 pregnant women during the second and third trimesters. Using multiple linear regression models adjusted for serum lipids, we evaluated factors predicting concentrations of 11 polychlorinated biphenyl (PCB) congeners, their sum, and several pesticides and metabolites. Variables evaluated were age, race, place of birth, date of blood draw, body mass index, occupation, past residence on a farm, parity, and duration of pregnancy at blood draw. Concentrations of highly chlorinated PCBs and the sum of the PCBs increased with age. Concentrations of certain PCB congeners, as well as the sum, were significantly higher among nonwhites and increased with calendar date of blood draw. (italic)p,p(/italic) -DDT and (italic)p,p(/italic) -DDE concentrations were about 50% higher for nonwhites compared with whites and for those born in California or the southeastern United States versus elsewhere in the United States. Higher body mass index was associated with lower concentrations of several PCBs and (italic)p,p(/italic) -DDE but with higher heptachlor epoxide and DDT levels. The increase in use of PCBs during the 1960s is apparently detectable as increasing concentrations in maternal sera between 1963 and 1967. Marked racial and regional differences in serum pesticide levels were likely caused by geographic variation in previous agricultural and vector-control uses. The relationship to body mass index appears to be complex.