Lusine Yaghjyan

Serum Biomarkers of Polyfluoroalkyl Compound Exposure in Young Girls in Greater Cincinnati and the San Francisco Bay Area, USA

PFC serum concentrations were measured in 6-8 year-old girls in Greater Cincinnati (GC) (N = 353) and the San Francisco Bay Area (SFBA) (N = 351). PFOA median concentration was lower in the SFBA than GC (5.8 vs. 7.3 ng/mL). In GC, 48/51 girls living in one area had PFOA concentrations above the NHANES 95th percentile for children 12-19 years (8.4 ng/mL), median 22.0 ng/mL. The duration of being breast fed was associated with higher serum PFOA at both sites and with higher PFOS, PFHxS and Me-PFOSA-AcOH concentrations in GC. Correlations of the PFC analytes with each other suggest that a source upriver from GC may have contributed to exposures through drinking water, and water treatment with granular activated carbon filtration resulted in less exposure for SWO girls compared to those in NKY. PFOA has been characterized as a drinking water contaminant, and water treatment systems effective in removing PFCs will reduce body burdens.

Estrogens in the breast tissue: a systematic review.

The role of estrogens in breast carcinogenesis has been investigated at the level of whole body (plasma) and cell (molecular, receptors, etc.). Growing attention focused on the breast tissue being an intracrine organ, with potentially important local estrogen production in the breast. However, very little is known about the local breast tissue estrogen levels. Understanding the role of the tissue estrogens in breast carcinogenesis might open new avenues in breast cancer prevention. This systematic review summarizes published studies that measured local estrogen levels in the breast and offers suggestions for strategies to fill gaps in our existing scientific knowledge.

Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort

Background:We investigated associations of known breast cancer risk factors with breast density, a well-established and very strong predictor of breast cancer risk.Methods:This nested case–control study included breast cancer-free women, 265 with high and 860 with low breast density. Women were required to be 40–80 years old and should have a body mass index (BMI) <35 at the time of the index mammogram. Information on covariates was obtained from annual questionnaires.Results:In the overall analysis, breast density was inversely associated with BMI at mammogram (P for trend<0.001), and parity (P for trend=0.02) and positively associated with alcohol consumption (ever vs never: odds ratio 2.0, 95% confidence interval 1.4–2.8). Alcohol consumption was positively associated with density, and the association was stronger in women with a family history of breast cancer (P<0.001) and in women with hormone replacement therapy (HRT) history (P<0.001). Parity was inversely associated with density in all subsets, except premenopausal women and women without a family history. The association of parity with density was stronger in women with HRT history (P<0.001).Conclusion:The associations of alcohol and parity with breast density appear to be in reverse direction, but stronger in women with a family history of breast cancer and women who ever used HRT.

Associations of urinary phthalates with body mass index, waist circumference and serum lipids among females: National Health and Nutrition Examination Survey 1999–2004

Background/objectives:Exposure to environmental chemicals could be one of the contributors to the increasing obesity epidemic. Very little is known about the association of phthalates, ubiquitous chemicals widely used in consumer products, with obesity and lipid metabolism. This study investigated the association of urinary phthalate metabolites and, for the first time, the ratios of the major metabolites of the most common phthalate, di-2-ethylhexyl phthalate, with body mass index (BMI), waist circumference and serum lipid levels in the US female population.Methods:This cross-sectional study used the data from the National Health and Nutrition Examination Survey, 1999–2004 and was restricted to women aged ⩾18 years, who were not pregnant and had no history of diabetes. Using multivariate ordered logistic regression, we examined associations of seven urinary phthalate metabolites and their metabolic ratios with the BMI, waist circumferences, total cholesterol, triglycerides and high- and low-density lipoprotein cholesterol.Results:BMI was positively associated with monobutyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) (odds ratio (OR)=1.13; 95% confidence interval (CI), 1.03–1.23 and OR=1.12; 95% CI, 1.03–1.23, respectively). Waist circumference was positively associated with MBP (OR=1.13; 95% CI, 1.03–1.24). A higher ratio of MEHP to mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was positively associated with both BMI (OR=1.21; 95% CI, 1.09–1.34) and waist circumference (OR=1.20; 95% CI, 1.10–1.31). There were no other significant associations.Conclusions:A higher metabolic ratio of MEHP to MEHHP, reflective of slower oxidative conversion of MEHP, is associated with greater BMI and waist circumference.

Physical activity and mammographic breast density: a systematic review

Studies show a protective relationship between physical activity and breast cancer risk across the life course from menarche to postmenopausal years. Mammographic breast density is a known and strong breast cancer risk factor. Whether the association of physical activity with breast cancer risk is mediated through mammographic breast density is poorly understood. This systematic review summarizes published studies that investigated the association between physical activity and mammographic breast density and discusses the methodological issues that need to be addressed. We included in this review studies that were published before October 31, 2011 that were accessible in full-text format and were published in English. We identified 20 studies through the PubMed Central, BioMed Central, Embase, and Scopus and using the search terms “physical activity and breast density” and “exercise and breast density” as well as through manual searches of the bibliographies of the articles identified in electronic searches. We found no evidence of association between physical activity and breast density across the studies by grouping them first by the timing of physical activity assessment (in adolescence, current/recent, past, and lifetime) and then by women’s menopausal status (premenopausal and postmenopausal). Given the strength of the relationship between physical activity and breast cancer and the null findings of this review, it is unlikely that the effect of physical activity is mediated through an effect on breast density.

Vitamin D and mammographic breast density: a systematic review

Studies suggest a protective relationship between Vitamin D and breast cancer risk. Several studies assessed the association of Vitamin D with mammographic breast density, a known and strong breast cancer risk factor. Understanding the potential role of Vitamin D in the modification of breast density might open new avenues in breast cancer prevention. This systematic review summarizes published studies that investigated the association between Vitamin D and mammographic breast density and offers suggestions for strategies to advance our scientific knowledge.

Moving microbiota research toward establishing causal associations that represent viable targets for effective public health interventions

PURPOSE There appears to be great promise in developing targeted interventions that exploit the complex interactions between commensal microbiota colonizing various anatomic sites and the health of the human host. Although data about variations in microbiota composition across various population groups are accumulating, there remains a limited understanding of the driving forces behind the observed intraindividual and interindividual differences in microbiota. METHODS Using information derived from research on gut microbiota, the anatomic site that harbors the highest numbers of bacteria and associated microbial functions, we emphasize the need for establishing causality of observed correlations. Progress to date in establishing microbiota-based targets for novel prevention and treatment approaches is reviewed, suggesting avenues for future research endeavors. RESULTS The complexities associated with the diverse interactions among environmental exposures, microbiota composition and activities and health of the human host require multidisciplinary study approaches to move knowledge beyond current descriptions of correlations without considerations of temporality and mechanisms. CONCLUSIONS Information gleaned from studies of the potential contributions of diet-mediated microbiota effects on colorectal carcinogenesis will be useful in designing future large population-based studies for determining the causal pathways for microbiota contributions to human health and disease.

Postmenopausal mammographic breast density and subsequent breast cancer risk according to selected tissue markers

Background:This study aimed to determine if associations of pre-diagnostic percent breast density, absolute dense area, and non-dense area with subsequent breast cancer risk differ by the tumour’s molecular marker status.Methods:We included 1010 postmenopausal women with breast cancer and 2077 matched controls from the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHS II) cohorts. Breast density was estimated from digitised film mammograms using computer-assisted thresholding techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Polychotomous logistic regression was used to assess associations of breast density measures with tumour subtypes by the status of selected tissue markers. All tests of statistical significance were two sided.Results:The association of percent density with breast cancer risk appeared to be stronger in ER− as compared with ER+ tumours, but the difference did not reach statistical significance (density ⩾50% vs <10% odds ratio (OR)=3.06, 95% confidence interval (CI) 2.17–4.32 for ER+; OR=4.61, 95% CI 2.36–9.03 for ER−, Pheterogeneity=0.08). Stronger positive associations were found for absolute dense area and CK5/6− and EGFR− as compared with respective marker-positive tumours (Pheterogeneity=0.002 and 0.001, respectively). Stronger inverse associations of non-dense area with breast cancer risk were found for ER− as compared with ER+ tumours (Pheterogeneity=0.0001) and for AR+, CK5/6+, and EGFR+ as compared with respective marker-negative tumours (Pheterogeneity=0.03, 0.005, and 0.009, respectively). The associations of density measures with breast cancer did not differ by progesterone receptor and human epidermal growth factor receptor 2 status.Conclusions:Breast density influences the risk of breast cancer subtypes by potentially different mechanisms.

Associations of individual characteristics and lifestyle factors with metabolism of di-2-ethylhexyl phthalate in NHANES 2001-2012.

BACKGROUND Previous studies suggest that a higher ratio of primary to secondary metabolites of di-2-ethylhexyl phthalate (DEHP), reflective of a slower DEHP conversion rate, is associated with a greater physiologic effect. We examined associations of several individual characteristics and lifestyle factors with the ratio of mono-2-ethylhexyl phthalate to mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHP:MEHHP) and %MEHP (the ratio of MEHP to the sum of the secondary metabolites). METHODS We used the data from the National Health and Nutrition Examination Survey, 2001-2012. The study included adults with BMI<30 and no diabetes. Pregnant women were excluded. We examined associations of age, race, gender, Body Mass Index, smoking, alcohol and caffeine consumption, medication use, cancer history, and menopausal status and postmenopausal hormone use (in women) with MEHP:MEHHP and %MEHP using multivariable linear regression. The values for %MEHP were log-transformed in the analysis. RESULTS In multivariable analysis, non-Caucasian individuals had higher %MEHP (non-Hispanic Blacks: β=0.114, 95% Confidence interval [CI]: 0.050, 0.177; Hispanic: β=0.089, 95% CI: 0.024, 0.154; other race: β=0.126, 95% CI: 0.033, 0.219). Age was inversely associated with MEHP:MEHHP (β=-0.001, 95% CI: -0.002, -0.001) and %MEHP (β=-0.006, 95% CI: -0.008, -0.004). Overweight individuals had lower MEHP: MEHHP and lower %MEHP (β=-0.035, 95% CI: 0.062, -0.008 and β=-0.104, 95% CI: -0.162, -0.046, respectively). Alcohol consumption was inversely associated with %MEHP among men (p-trend=0.03). CONCLUSIONS Individual and lifestyle characteristics are associated with differences in DEHP metabolism. Understanding underlying biological mechanisms could help to identify individuals at a greater risk of adverse effects from DEHP exposure.

Adolescent fiber intake and mammographic breast density in premenopausal women.

BackgroundTo date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent fiber intake with mammographic density in premenopausal women.MethodsThis study included 743 cancer-free premenopausal women (mean age, 44.9 years) within the Nurses’ Health Study II cohort. Percent breast density, absolute dense and non-dense areas were measured from digitized film mammograms using a computer-assisted thresholding technique. Adolescent and adult diet were assessed with a food frequency questionnaire; energy-adjusted nutrient intakes were estimated for each food item. Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations between quartiles of adolescent fiber intake and each of the breast density measures, adjusted for potential confounders. Associations were examined separately for total fiber intake; fiber from fruits, vegetables, legumes, and cereal; and food sources of fiber (fruits, vegetables, and nuts).ResultsIn multivariable analyses, total fiber intake during adolescence was not associated with percent breast density (p for trend = 0.64), absolute dense area (p for trend = 0.80), or non-dense area (p for trend = 0.75). Similarly, neither consumption of fiber from fruits, vegetables, legumes, or cereal nor specific sources of fiber intake (fruits, vegetables, or nuts) during adolescence were associated with any of the mammographic density phenotypes.ConclusionsOur findings do not support the hypothesis that adolescent fiber intake is associated with premenopausal mammographic breast density.