Karin B Michels

Universitätsklinikum Freiburg, Freiburg an der Elbe, Lower Saxony, Germany

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Publications (216)1642.69 Total impact

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    ABSTRACT: Regular milk consumption during childhood and adolescence is recommended for bone health. However, milk consumption increases circulating insulin-like growth factor I concentrations, and may also accelerate puberty. We prospectively investigated the association between milk consumption and age at menarche in the Growing Up Today Study. Study participants were 5583 US girls who were premenarcheal and ages 9-14 y in 1996. Girls were followed through 2001, at which time 97% of noncensored participants had reported menarche. Frequency of milk and meat consumption was calculated with the use of annual youth/adolescent food frequency questionnaires from 1996-1998. Intake of related nutrients was also measured. Age at menarche was self-reported annually through 2001. During follow-up, 5227 girls attained menarche over 10,555 accrued person-years. In models adjusted for dietary and sociodemographic predictors of menarche, frequency of milk consumption did not predict age at onset of menarche (for >3 glasses of milk/d vs. 1.1-4 glasses/wk, HR: 0.93; 95% CI: 0.83, 1.04). After additional adjustment for body size, premenarcheal girls consuming >3 glasses of milk daily were 13% less likely (95% CI: -3%, -23%; P-trend: <0.01) to attain menarche in the next month relative to those consuming 1.1-4 glasses/wk. Neither total meat nor red meat consumption was associated with age at menarche. Our findings suggest that regular consumption of milk in girls aged ≥9 y is unlikely to substantially affect age at onset of menarche. Studies assessing associations between diet in early childhood and pubertal timing may be more illuminating. © 2015 American Society for Nutrition.
    Journal of Nutrition 07/2015; DOI:10.3945/jn.115.214270 · 4.23 Impact Factor
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    ABSTRACT: There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may impact disease propensity through epigenetic mechanisms. The objective of this study was to determine if prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and if miRNA alterations are associated with birth outcomes. Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR. For three miRNAs, miR-142-3p, miR15a-5p, and miR-185, we detected associations between ∑phthalates or ∑phenols on expression levels (p<0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden. Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans.
    Environmental Health Perspectives 06/2015; DOI:10.1289/ehp.1408409 · 7.03 Impact Factor
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    ABSTRACT: Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 05/2015; DOI:10.1200/JCO.2014.59.1602 · 18.43 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate whether antihypertensive medication use, including long-term use, is associated with increased breast cancer incidence in women. We studied 210,641 U.S. registered nurses participating in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Information on antihypertensive medication use was collected on biennial questionnaires in both cohorts, and breast cancer cases were ascertained during this period. Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of invasive breast cancer over follow-up (1988-2012 in NHS, 1989-2011 in NHS II) across categories of overall antihypertensive medication use and use of specific classes (diuretics, beta blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors). During follow-up, 10,012 cases of invasive breast cancer developed (6718 cases in NHS and 3294 in the NHS II). Overall, current use of any antihypertensive medication was not associated with breast cancer risk compared with past/never use in NHS (multivariable-adjusted relative risk = 1.00, 95 % CI = 0.95-1.06) or NHS II (multivariable-adjusted relative risk = 0.94, 95 % CI = 0.86-1.03). Furthermore, no specific class of antihypertensive medication was consistently associated with breast cancer risk. Results were similar when we considered hypertensive women only, and when we evaluated consistency and duration of medication use over time. Overall, antihypertensive medication use was largely unrelated to the risk of invasive breast cancer among women in the NHS cohorts.
    Breast Cancer Research and Treatment 02/2015; 150(1). DOI:10.1007/s10549-015-3311-9 · 4.20 Impact Factor
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    ABSTRACT: Is sugar-sweetened beverage (SSB) consumption associated with age at menarche? More frequent SSB consumption was associated with earlier menarche in a population of US girls. SSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated. The Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche. Cumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression. More frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ≤2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ≤2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche. Although we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure. More frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption. The Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Reproduction 01/2015; 30(3). DOI:10.1093/humrep/deu349 · 4.59 Impact Factor
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    ABSTRACT: Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 members of the Nurses' Health Study (NHS) and 105,386 of the Nurses' Health Study II (NHS II) recalled their body fatness at ages 5, 10, and 20 using a pictogram. Childhood and adolescent body fatness were derived as the average at ages 5 and 10, and ages 10 and 20, respectively. We obtained adult weight from concurrent questionnaires. We calculated hazard ratios (HR) of endometrial cancer using Cox proportional hazards models. During follow-up, 757 incident cases of endometrial cancer were diagnosed. Body fatness in childhood, at age 10, in adolescence, and at age 20 were positively associated with endometrial cancer risk (HR for ≥ Level 5 versus ≤ Level 2 in adolescence: 1.83 (95% CI 1.41-2.37). After adjusting for most recent BMI, none of the associations persisted. Weight change since age 18 was positively associated with endometrial cancer risk [HR for ≥ 25 kg gain versus stable: 2.54 (95% CI 1.80-3.59). Adult BMI was strongly associated with endometrial cancer risk [HR BMI ≥ 35 kg/m2 versus BMI ≤ 25 kg/m2: 4.13 (95% CI 3.29-5.16)]. In postmenopausal women, the association with BMI was significantly stronger among non-users of hormone therapy. In conclusion, obesity throughout life is positively associated with endometrial cancer risk, with adult obesity one of the strongest risk factors. Maintaining a healthy weight throughout life remains important. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 01/2015; 137(3). DOI:10.1002/ijc.29427 · 5.01 Impact Factor
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    ABSTRACT: Epigenetic regulation of imprinted genes enables monoallelic expression according to parental origin, and its disruption is implicated in many cancers and developmental disorders. The expression of hormone receptors is significant in breast cancer as they are indicators of cancer cell growth rate and determine response to endocrine therapies. We investigated the frequency of aberrant events and variation in DNA methylation at nine imprinted sites in invasive breast cancer and examined the association with estrogen and progesterone receptor status. Breast tissue and blood from patients with invasive breast cancer (n=38) and benign breast disease (n=30) were compared to those from healthy individuals (n=36), matched to the cancer patients by age at diagnosis, ethnicity, BMI, menopausal status, and familial history of cancer. DNA methylation and allele-specific expression were analyzed by pyrosequencing. Tumor-specific methylation changes at IGF2 DMR2 were observed in 59% of cancer patients, IGF2 DMR0 in 38%, DIRAS3 DMR in 36%, GRB10 ICR in 23%, PEG3 DMR in 21%, MEST ICR in 19%, H19 ICR in 18%, KvDMR in 8%, and SNRPN/SNURF ICR in 4%. Variation of methylation was significantly greater in breast tissue from cancer patients than healthy individuals and benign breast disease. Aberrant methylation of three or more sites was significantly associated with negative estrogen-alpha (Fisher's Exact Test, p=0.02) and progesterone-A (p=0.02) receptor status. Aberrant events and increased variation of imprinted gene DNA methylation therefore appear to be frequent in invasive breast cancer and are associated with negative estrogen and progesterone receptor status, without loss of monoallelic expression. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 01/2015; DOI:10.1002/ijc.29419 · 5.01 Impact Factor
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    ABSTRACT: Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer. Copyright © 2014, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 12/2014; 24(3). DOI:10.1158/1055-9965.EPI-14-1009 · 4.32 Impact Factor
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    ABSTRACT: Background:Data from previous studies consistently suggest that maternal smoking is positively associated with the risk of obesity later in life. Whether this association persists across generations is unknown. Methods:We investigated the association between grandparent smoking status and grandchild overweight status among 3101 grandmother-mother-child triads in the Nurses’ Health Study II (NHS II), the NHS Mothers’ Cohort Study, and the children of NHS II participants who are in the Growing up Today Study (GUTS). Grandmothers of children provided information on their and their partner’s smoking during pregnancy with the child’s mother. Information on child's weight and height at ages 12 and 17 was obtained by self-report from the GUTS questionnaires. We used logistic regression to estimate odds ratios (ORs) of being overweight or obese, relative to normal weight. Results: Seventy-five percent of grandmothers reportedly did not smoke during pregnancy, while 4% quit during pregnancy, 13% continued smoking up to 14 cigarettes/day, and 7% smoked 15+ cigarettes daily throughout pregnancy. Grand-maternal smoking was not associated with being overweight or obese at age 12 or 17 years, in boys or in girls. After adjusting for multiple covariates, the OR of being overweight or obese relative to normal weight at age 12 years in girls whose grandmothers smoked 15+ cigarettes per day during pregnancy with their mothers was 1.23 (95% CI 0.75-2.01; ptrend = 0.25) and 1.08 (0.65-1.97; ptrend = 0.34) in boys. Grand-paternal smoking was positively associated with being overweight or obese at age 12 years in girls but not boys, and not at age 17 years for either: the OR for being overweight or obese at age 12 years was 1.46 (95% CI 1.07-1.99; ptrend = 0.01) in girls, and 1.26 (95% CI 0.94-1.70; ptrend = 0.11) in boys. After restricting to children of non-smoking mothers, the comparable OR for granddaughter obesity was attenuated and no longer significant [OR 1.35 (95% CI 0.93-1.97; ptrend= 0.10)]. Conclusions: Our findings suggest that grand-maternal smoking is not associated with adolescent overweight status in the grandchild. However, grand-paternal smoking may affect overweight status of the granddaughter, likely through the association between grand-paternal smoking and maternal smoking.
    142nd APHA Annual Meeting and Exposition 2014; 11/2014
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    ABSTRACT: Objective To determine whether use of oral contraceptives is associated with all cause and cause specific mortality. Design Prospective cohort study. Setting Nurses’ Health Study, data collected between 1976 and 2012. Population 121 701 participants were prospectively followed for 36 years; lifetime oral contraceptive use was recorded biennially from 1976 to 1982. Main outcome measures Overall and cause specific mortality, assessed throughout follow-up until 2012. Cox proportional hazards models were used to calculate the relative risks of all cause and cause specific mortality associated with use of oral contraceptives. Results In our population of 121 577 women with information on oral contraceptive use, 63 626 were never users (52%) and 57 951 were ever users (48%). After 3.6 million person years, we recorded 31 286 deaths. No association was observed between ever use of oral contraceptives and all cause mortality. However, violent or accidental deaths were more common among ever users (hazard ratio 1.20, 95% confidence interval 1.04 to 1.37). Longer duration of use was more strongly associated with certain causes of death, including premature mortality due to breast cancer (test for trend P<0.0001) and decreased mortality rates of ovarian cancer (P=0.002). Longer time since last use was also associated with certain outcomes, including a positive association with violent or accidental deaths (P=0.005). Conclusions All cause mortality did not differ significantly between women who had ever used oral contraceptives and never users. Oral contraceptive use was associated with certain causes of death, including increased rates of violent or accidental death and deaths due to breast cancer, whereas deaths due to ovarian cancer were less common among women who used oral contraceptives. These results pertain to earlier oral contraceptive formulations with higher hormone doses rather than the now more commonly used third and fourth generation formulations with lower estrogen doses.
    BMJ Clinical Research 10/2014; 349:g6356. DOI:10.1136/bmj.g6356 · 14.09 Impact Factor
  • Epigenomics of Common Diseases, Cambridge, UK; 10/2014
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    ABSTRACT: The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called "ID Screen") for feasibility and validity.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 10/2014; 57(11). DOI:10.1007/s00103-014-2052-y · 1.01 Impact Factor
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    ABSTRACT: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components.
    Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz 10/2014; 57(11). DOI:10.1007/s00103-014-2048-7 · 1.01 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):2166-2166. DOI:10.1158/1538-7445.AM2014-2166 · 9.28 Impact Factor
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    ABSTRACT: It remains unclear if oral contraceptive (OC) use is associated with the incidence of colorectal cancer. Few studies have examined this association by duration of OC use, time since last OC use, and different cancer subsites. Among 88,691 participants of the Nurses' Health Study I (NHSI) and 93,080 participants of the Nurses' Health Study II (NHSII), we assessed OC use every 2 years between 1976-2010 and categorized it as ever use, duration of use, and time since last use. We included incident colorectal cancer cases through 2010 (NHSI: age at diagnosis=36-88, N=1,764, NHSII: age at diagnosis=33-64, N=206). Multivariable hazard ratios and 95% confidence intervals [HR (95% CIs)] were estimated using Cox proportional hazards regression models. Ever OC use was not associated with colorectal cancer in NHSI [1.01 (0.91, 1.12)] nor NHSII [1.03 (0.69, 1.53)]. In NHSII, when compared to never-users, longer durations (5+ years) of OC use were inversely associated with the risk of colon cancers (test for trend p=0.02) but the number of endpoints was limited. No other colorectal cancer subsites were associated with OC durations or times since last OC use in either cohort. In two large prospective cohorts, we found little evidence that OC use may be protective for colorectal cancer, except potentially with longer durations of use among younger women. Our results do not support the previous initial studies that reported an inverse association of recent OC use with colorectal cancer but instead support newer, larger studies demonstrating no such association. Copyright © 2015, American Association for Cancer Research.
    Dana Farber/Harvard Cancer Center’s Celebration of Junior Investigators in Cancer Research, Boston, MA; 09/2014
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    Timothy M Barrow, Karin B Michels
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    ABSTRACT: Epigenetic epidemiology includes the study of variation in epigenetic traits and the risk of disease in populations. Its application to the field of cancer has provided insight into how lifestyle and environmental factors influence the epigenome and how epigenetic events may be involved in carcinogenesis. Furthermore, it has the potential to bring benefit to patients through the identification of diagnostic markers that enable the early detection of disease and prognostic markers that can inform upon appropriate treatment strategies. However, there are a number of challenges associated with the conduct of such studies, and with the identification of biomarkers that can be applied to the clinical setting. In this review, we delineate the challenges faced in the design of epigenetic epidemiology studies in cancer, including the suitability of blood as a surrogate tissue and the capture of genome-wide DNA methylation. We describe how epigenetic epidemiology has brought insight into risk factors associated with lung, breast, colorectal and bladder cancer and review relevant research. We discuss recent findings on the identification of epigenetic diagnostic and prognostic biomarkers for these cancers.
    Biochemical and Biophysical Research Communications 08/2014; 455(1-2). DOI:10.1016/j.bbrc.2014.08.002 · 2.28 Impact Factor
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    ABSTRACT: OBJECTIVE We evaluated the associations of both maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters and explored whether any association was explained by weight at birth or BMI throughout life. RESEARCH DESIGN AND METHODS We used data from 34,453 participants of the Nurses' Health Study II. We used Cox proportional hazards models to examine the associations of maternal and paternal smoking during pregnancy with incidence of type 2 diabetes in daughters between 1989 and 2009. RESULTS Maternal smoking during the first trimester only was associated with the risk of type 2 diabetes in the offspring, independent of confounders, birth weight, and later-life BMI (fully adjusted hazard ratio 1.34 [95% CI 1.01, 1.76]). In the age-adjusted models, both continued maternal smoking during pregnancy and paternal smoking tended to be associated with an increased risk of type 2 diabetes in daughters. Perinatal and adult life variables did not explain these associations, but additional adjustment for current BMI fully attenuated the effect estimates. CONCLUSIONS The associations of maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters were largely explained by BMI throughout the life course. Further studies are needed to explore the role of first-trimester-only maternal smoking on insulin resistance in the offspring. Also, similar effect estimates for maternal and paternal smoking suggest that the associations reflect shared family-based or lifestyle-related factors.
    Diabetes Care 08/2014; 37(11). DOI:10.2337/dc13-1679 · 8.57 Impact Factor
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    ABSTRACT: Genomic imprinting leads to parent-of-origin specific gene expression and is determined by epigenetic modification of genes. The paternally expressed gene insulin-like growth-factor 2 (IGF2) is located about ~100kb from the maternally expressed non-coding gene H19 on human chromosome 11, and both genes play major roles in embryonic and placental growth. Given adverse gestational environments can influence DNA methylation patterns in extra-embryonic tissues, we hypothesized that prenatal exposure to endocrine disrupting chemicals (EDCs) alters H19 and IGF2 methylation in placenta. Our study was restricted to a total of 196 women co-enrolled in the Predictors of Preeclampsia Study and the Harvard Epigenetic Birth Cohort. First trimester urine concentrations of 8 phenols and 11 phthalate metabolites were measured and used to characterize EDC exposure profiles. We assessed methylation of differentially methylated regions (DMRs) by pyrosequencing of H19, IGF2DMR0, and IGF2DMR2 and correlated values with phenol and phthalate metabolites. We also assessed overall expression and allele-specific expression of H19 and IGF2. We found several significant associations between DNA methylation and additive biomarker measurements. A significant decrease in H19 methylation was associated with high levels of the sum (Σ) of phthalate metabolites and metabolites of low molecular weight (LMW) phthalates. Σphthalate and LMW phthalate concentrations were inversely associated with IGF2DMR0 methylation values. Variation in methylation was not associated with changes in allele-specific expression. However increased deviation of allele-specific expression of H19 was associated with Σdi(2-ethylhexyl) phthalate metabolites and high molecular weight phthalates. Neither methylation nor expression of these imprinted regions had a significant impact on birth length or birth weight. Overall, our study provides new insight into an epigenetic mechanism that occurs following EDC exposure.
    Environmental Research 06/2014; 133. DOI:10.1016/j.envres.2014.04.032 · 3.95 Impact Factor
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    ABSTRACT: Background/Objectives In animal studies, exposure to multi-vitamins may be associated with obesity in the offspring; however, data in humans is sparse. We therefore examined the association between prenatal vitamin intake during pregnancy and offspring obesity. Subjects/Methods We investigated the association between prenatal vitamin intake and obesity among 29 160 mother-daughter dyads in the Nurses’ Health Study II. Mothers of participants provided information on prenatal vitamin use during pregnancy with the nurse daughter. Information on body fatness at ages 5 and 10, body mass index (BMI) at age 18, weight in 1989 and 2009, waist circumference, and height was obtained from the daughter. Polytomous logistic regression was used to predict BMI in early adulthood and adulthood, and body fatness in childhood. Linear regression was used to predict waist circumference in adulthood. Results In utero exposure to prenatal vitamins was not associated with body fatness, either in childhood or adulthood. Women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted odds ratio of being obese in adulthood of 0.99 (95% CI 0.92 – 1.05, P-value = 0.68) compared to women whose mothers did not take prenatal vitamins. Women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted odds ratio of having the largest body shape at age 5 of 1.02 (95% CI 0.90 – 1.15, P-value = 0.78). In additional analyses, in utero exposure to prenatal vitamins was also unrelated to adult abdominal adiposity. Conclusions Exposure to prenatal vitamins was not associated with body fatness either in childhood or in adulthood.
    International journal of obesity (2005) 06/2014; 39(1). DOI:10.1038/ijo.2014.107 · 5.39 Impact Factor
  • Society for Epidemiologic Research Annual Conference, Seattle, WA; 06/2014

Publication Stats

7k Citations
1,642.69 Total Impact Points


  • 2014–2015
    • Universitätsklinikum Freiburg
      • Institute of Tumor Prevention and Epidemiology
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2000–2015
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 2011–2014
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
    • University of North Carolina at Chapel Hill
      • Department of Obstetrics and Gynecology
      North Carolina, United States
  • 1996–2014
    • Harvard Medical School
      • • Department of Obstetrics, Gynecology, and Reproductive Biology
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2012
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States
  • 1998–2012
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Department of Obstetrics and Gynecology
      Boston, Massachusetts, United States
  • 2004–2005
    • University of Cambridge
      • Cambridge Institute of Public Health
      Cambridge, England, United Kingdom
  • 2002
    • Karolinska Institutet
      • Institute of Environmental Medicine - IMM
      Сольна, Stockholm, Sweden
  • 1999
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States