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ABSTRACT: Imprinted genes are monoallelically expressed according to the parent of origin and are critical for proper placental and embryonic development. Disruption of methylation patterns at imprinted loci resulting in loss of imprinting (LOI) may lead to serious imprinting disorders (e.g., Beckwith-Wiedemann syndrome) and is described in some cancers (e.g., Wilms' tumor). As most research has focused on children with cancer or other abnormal phenotypes, the imprinting status in healthy infants at birth has not been characterized. We examined the prevalence of H19 and IGF2 LOI at birth by allele-specific expression assays analysis on 114 human individuals. Overall expression and methylation analyses were performed on a subset of samples. We found that LOI of H19 was observed for 4% of individuals in cord blood and 3.3% in placenta, and for IGF2 of 22% of individuals in the cord blood and 0% in placenta. Interestingly, LOI status did not correspond to aberrant methylation levels of the imprinted DMRs or with changes in overall gene expression for the majority of individuals. Our observations suggest that LOI is present in phenotypically healthy infants. Determining a "normal" human epigenotype range is important for discovering factors required to maintain a healthy pregnancy and embryonic development.-Rancourt, R. C., Harris, H. R., Barault, L., Michels, K. B. The prevalence of loss of imprinting of H19 and IGF2 at birth.
The FASEB Journal 04/2013; · 5.71 Impact Factor
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ABSTRACT: OBJECTIVE: Human papillomavirus (HPV) infections and abnormal Pap test results are common, and most do not progress to cervical cancer. Because it is difficult to predict which mild Pap abnormalities will develop into precancerous lesions, many women undergo painful and costly evaluations and even unnecessary treatment. The objective of this study was to develop a risk prediction model based on clinical and demographic information to identify women most likely to develop significant precancerous lesions (cervical intraepithelial neoplasia grades 2/3 [CIN 2/3] or adenocarcinoma in situ [AIS]) among women with mild Pap abnormalities (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion). MATERIALS AND METHODS: The Abnormal Pap Smear Registry includes women who received treatment at the Brigham and Women's Hospital/Dana Farber Cancer Institute Pap Smear Evaluation Center beginning in 2006. It includes 1,072 women with mild cervical dysplasia (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) on their referral Pap test. We derived a clinical prediction model to predict the probability of developing CIN 2/3 or AIS using multivariate logistic regression with a split-sample approach. RESULTS: By the end of the follow-up, 93 of the 1,072 women developed CIN 2/3 or AIS (8.7%). There were several differences between women who developed CIN 2/3 or AIS and women who did not. However, once we put these into the regression model, the only variable that was significantly associated with CIN 2/3 or AIS was having a history of an abnormal Pap or biopsy result (odds ratio = 2.44; 95% CI =1.03-5.76). The resulting prediction model had poor discriminative ability and was poorly calibrated. CONCLUSIONS: Despite accounting for known risk factors, we were unable to predict individual patients' probability for progression on the basis of available data.
Journal of Lower Genital Tract Disease 03/2013; · 1.07 Impact Factor
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ABSTRACT: PURPOSE: Physical and sexual abuse are prevalent social hazards. We sought to examine the association between childhood physical and sexual abuse and age at menarche. METHODS: Among 68,505 participants enrolled in the Nurses' Health Study II, we investigated the association between childhood physical abuse and sexual abuse and menarche before age 11 years (early) or after age 15 years (late) using multivariate logistic regression analysis, mutually adjusting for both types of abuse. RESULTS: Fifty-seven percent of respondents reported some form of physical or sexual abuse in childhood. We found a positive dose-response association between severity of sexual abuse in childhood and risk for early menarche. Compared with women who reported no childhood sexual abuse, the adjusted odds ratio (AOR) for early menarche in women who reported childhood sexual abuse was 1.20 (95% confidence interval [CI]: 1.10, 1.37) for sexual touching and 1.49 (95% CI: 1.34, 1.66) for forced sexual activity. Severe physical abuse predicted early menarche (AOR = 1.22, 95% CI: 1.10, 1.37). Childhood physical abuse had a dose-response association with late age at menarche: AOR 1.17 (95% CI: 1.04, 1.32) for mild, 1.20 (95% CI: 1.08, 1.33) for moderate, and 1.50 (95% CI: 1.27, 1.77) for severe physical abuse. Sexual abuse was not associated with late menarche. CONCLUSIONS: Childhood abuse was prevalent in this large cohort of U.S. women. Severity of childhood sexual abuse was associated with risk for early onset of menarche, and physical abuse was associated with both early and late onset of menarche.
Journal of Adolescent Health 02/2013; 52(2):241-247. · 3.33 Impact Factor
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ABSTRACT: There is growing interest in identifying surrogate tissues to identify epimutations in cancer patients since primary target tissues are often difficult to obtain. Methylation patterns at imprinted loci are established during gametogenesis and post fertilization and their alterations have been associated with elevated risk of cancer. Methylation at several imprinted differentially methylated regions (GRB10 ICR, H19 ICR, KvDMR, SNRPN/SNURF ICR, IGF2 DMR0, and IGF2 DMR2) were analyzed in DNA from leukocytes and mammary tissue (normal, benign diseases, or malignant tumors) from 87 women with and without breast cancer (average age of cancer patients: 53; range: 31-77). Correlations between genomic variants and DNA methylation at the studied loci could not be assessed, making it impossible to exclude such effects. Methylation levels observed in leukocyte and mammary tissue DNA were close to the 50% expected for monoallellic methylation. While no correlation was observed between leukocyte and mammary tissue DNA methylation for most of the analyzed imprinted genes, Spearman's correlations were statistically significant for IGF2 DMR0 and IGF2 DMR2, although absolute methylation levels differed. Leukocyte DNA methylation levels of selected imprinted genes may therefore serve as surrogate markers of DNA methylation in cancer tissue.
PLoS ONE 01/2013; 8(2):e55896. · 4.09 Impact Factor
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ABSTRACT: Fetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33 086 participants of the Nurses' Health Study II and the Nurses' Mothers' Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8575 (25.9%) mothers and 18 874 (57.0%) fathers smoked during pregnancy. During follow-up, 7825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥15 cigarettes/d during pregnancy were associated with increased risks of hypertension (rate ratio, 1.19; 95% CI, 1.09-1.29; and rate ratio, 1.18; 95% CI, 1.12-1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, whereas additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (rate ratio, 1.07; 95% CI, 0.98-1.16; and rate ratio, 1.06; 95% CI, 1.01-1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.
Hypertension 12/2012; · 6.21 Impact Factor
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JAMA The Journal of the American Medical Association 11/2011; 306(20):2218-20. · 30.03 Impact Factor
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ABSTRACT: Never or curtailed lactation has been associated with an increased risk for incident hypertension, but the effect of exclusive breastfeeding is unknown. The authors conducted an observational cohort study of 55,636 parous women in the US Nurses' Health Study II. From 1991 to 2005, participants reported 8,861 cases of incident hypertension during 660,880 person-years of follow-up. Never or curtailed lactation was associated with an increased risk of incident hypertension. Compared with women who breastfed their first child for ≥12 months, women who did not breastfeed were more likely to develop hypertension (hazard ratio (HR) = 1.27, 95% confidence interval (CI): 1.18, 1.36), adjusting for family history and lifestyle covariates. Women who never breastfed were more likely to develop hypertension than women who exclusively breastfed their first child for ≥6 months (HR = 1.29, 95% CI: 1.20, 1.40). The authors found similar results for women who had never breastfed compared with those who had breastfed each child for an average of ≥12 months (HR = 1.22, 95% CI: 1.13, 1.32). In conclusion, never or curtailed lactation was associated with an increased risk of incident maternal hypertension, compared with the recommended ≥6 months of exclusive or ≥12 months of total lactation per child, in a large cohort of parous women.
American journal of epidemiology 11/2011; 174(10):1147-58. · 5.59 Impact Factor
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ABSTRACT: Body mass is inversely related to breast cancer risk among premenopausal women. Leptin, an essential cytokine regulating food intake, energy expenditure, glucose, and fat metabolism may be part of the mechanistic pathway. We investigated 50 tagging and candidate SNPs in the leptin (LEP) and leptin receptor (LEPR) genes for associations with premenopausal breast cancer incidence using 405 cases and 810 controls nested within the Nurses' Health Study II. We also examined associations between these SNPs and circulating leptin (among 910 women) and breast cancer grade (among 267 patients). Permutation tests were performed to adjust for multiple testing. We did not detect a significant association between SNPs in the LEP or LEPR gene and either breast cancer incidence or plasma leptin levels. Among cases, 14 SNPs of the LEPR gene were significantly associated with cancer grade, and rs1137101 (Q223R) survived multiple testing adjustment (adjusted P = 0.04). The G carriers of rs1137101 were more likely to have poorly differentiated than well-differentiated cancers. Our data suggest that common genetic variation in the LEP or LEPR gene has no strong association with premenopausal breast cancer risk. The LEPR gene might be associated with breast cancer grade.
Breast Cancer Research and Treatment 09/2011; 131(1):17-25. · 4.43 Impact Factor
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ABSTRACT: Adult body mass index (BMI) is inversely associated with premenopausal breast cancer risk, and childhood and adolescent body size is inversely associated with breast cancer risk in pre- and postmenopausal women. Breast density is inversely related to body size and may play a role in the association of body size with breast cancer risk. The authors conducted a nested case-control study including 1,528 cases and 2,844 controls from the Nurses' Health Study (1989-2004) and Nurses' Health Study II (1996-2003). Prior to breast cancer diagnosis, participants reported their body fatness during childhood and adolescence, BMI at age 18 years, and current BMI. Mammographic density was measured by using a computer-assisted thresholding method. The inverse association between adult BMI and premenopausal breast cancer (for BMI ≥30 vs. BMI 20-22.4, odds ratio = 0.64, 95% confidence interval: 0.38, 1.06) (P(trend) = 0.36) became positive after adjustment for mammographic density (odds ratio = 1.28, 95% confidence interval: 0.72, 2.30) (P(trend) = 0.07). Conversely, the inverse association between childhood and adolescent body size and breast cancer risk remained after adjustment for mammographic density. The inverse association between adult BMI and premenopausal breast cancer risk may be partially due to negative confounding by mammographic density. Conversely, mammographic density does not appear to explain the inverse association between childhood and adolescent body fatness and breast cancer risk.
American journal of epidemiology 09/2011; 174(8):909-18. · 5.59 Impact Factor
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ABSTRACT: Vitamin D may have a protective role in the etiology of multiple sclerosis (MS), but the effect of gestational vitamin D on adult onset MS has not been studied.
In 2001, 35,794 mothers of participants of the Nurses' Health Study II completed a questionnaire inquiring about their experiences and diet during pregnancy with their nurse daughters. We studied the association of maternal milk intake, maternal dietary vitamin D intake, and predicted maternal serum 25-hydroxyvitamin D (25(OH)D) during pregnancy and their daughters' risk of developing MS.
MS was diagnosed in 199 women. The relative risk of MS was lower among women born to mothers with high milk or vitamin D intake during pregnancy. The multivariate adjusted rate ratio (RR) of MS was 0.62 (95% confidence interval [CI], 0.40-0.95; p trend = 0.001) for nurses whose mothers consumed 2 to 3 glasses of milk per day compared with those whose mothers consumed <3 glasses per month, and 0.57 (95% CI, 0.35-0.91; p trend = 0.002) for nurses with mothers in the highest quintile of dietary vitamin D intake compared with those in the lowest. The predicted 25(OH)D level in the pregnant mothers was also inversely associated with the risk of MS in their daughters. Comparing extreme quintiles, the adjusted RR was 0.59; (95% CI, 0.37-0.92; p trend = 0.002).
Higher maternal milk and vitamin D intake during pregnancy may be associated with a lower risk of developing MS in offspring.
Annals of Neurology 07/2011; 70(1):30-40. · 11.09 Impact Factor
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ABSTRACT: Sexual development begins in utero and enters a dormant phase during infancy. The influence of maternal gestational weight gain (GWG) on daughter's age at menarche has not been explored.
We investigated the association between maternal GWG and age at menarche (<11 years, 11-15 years, >15 years of age) in a large cohort study of U.S. nurses, The Nurses' Health Study II (NHS II), and the Nurses' Mothers' Cohort Study.
Among 32,218 respondents, 7% reported age at menarche <l1, 90% aged 11-15 years, and 3% > age 15. Compared with women whose mothers gained 20-29 lbs during pregnancy, those whose mothers reported <10 lbs or >40 lbs of GWG were 30% more likely to report early onset menarche (<11 years of age) in logistic regression models adjusted for sociodemographic and maternal characteristics, and childhood body size and physical activity: adjusted odds ratio (OR) 1.31, 95% confidence interval (CI) 1.05-1.62, and 1.27, 95% CI 1.06-1.56. Maternal GWG was not associated with late menarche in the fully adjusted model (p(trend)=0.07).
These results suggest that either extreme of maternal GWG may influence risk for early age at menarche in daughters. Maternal GWG may be a modifiable risk factor for early menarche.
Journal of Women s Health 06/2011; 20(8):1193-200. · 1.57 Impact Factor
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ABSTRACT: Body mass index (BMI) is inversely related to the risk of premenopausal breast cancer, but the underlying biological mechanisms of this association are poorly understood. Leptin, a peptide hormone produced primarily by adipocytes, is a potential mediator of the BMI association because BMI and total body fat are positively associated with circulating leptin levels and leptin and its receptor are overexpressed in breast tumors. We conducted a prospective case-control study nested within the Nurses' Health Study II cohort examining the association between plasma leptin levels in premenopausal women and breast cancer risk. Leptin was measured in blood samples collected between 1996 and 1999. The analysis included 330 incident breast cancer cases diagnosed after blood collection and 636 matched controls. Logistic regression models, controlling for breast cancer risk factors, were used to calculate ORs and 95% CIs. After adjustment for BMI at age 18, weight change since age 18 to blood draw, and other breast cancer risk factors, plasma leptin levels were inversely associated with breast cancer risk (OR for top vs. bottom quartile = 0.55; 95% CI = 0.31-0.99; P(trend) = 0.04). Adjustment for BMI at blood draw attenuated the association (OR = 0.69; 95% CI = 0.38-1.23; P(trend) = 0.26). Our results suggest that leptin may be inversely associated with breast cancer risk, but it is unclear whether any part of this association is independent of BMI.
Cancer Prevention Research 06/2011; 4(9):1449-56. · 4.91 Impact Factor
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ABSTRACT: Bisphenol A (BPA) is a chemical suspected of causing endocrine and metabolic disruption in animals and humans. In rodents, in utero exposure to low-dose BPA is associated with weight gain. Detectable levels of BPA are found in most Americans due to its widespread use in the manufacture of food and drink packaging. We hypothesized that urinary BPA concentrations would be positively associated with general and central obesity.
Cross-sectional analysis of urinary BPA concentrations, body mass index, and waist circumference in 2747 adults (aged 18-74), using pooled data from the 2003/04 and 2005/06 National Health and Nutrition Examination Surveys.
The creatinine-adjusted geometric mean urinary BPA concentration was 2.05μg/g creatinine (25th percentile: 1.18, 75% percentile: 3.33). Relative to those in the lowest BPA quartile, participants in the upper BPA quartiles were more likely to be classified as obese (quartile 2 odds ratio (OR): 1.85, 95% confidence interval (CI): 1.22, 2.79; quartile 3 OR: 1.60, 95% CI: 1.05-2.44; quartile 4 OR: 1.76, 95% CI: 1.06-2.94). Higher BPA concentration was also associated with abdominal obesity (quartile 2 OR: 1.62, 95% CI: 1.11, 2.36; quartile 3 OR: 1.39, 95% CI: 1.02-1.90; quartile 4 OR: 1.58, 95% CI: 1.03-2.42).
Higher BPA exposure is associated with general and central obesity in the general adult population of the United States. Reverse causation is of concern due to the cross-sectional nature of this study; longitudinal studies are needed to clarify the direction of the association.
Environmental Research 06/2011; 111(6):825-30. · 3.40 Impact Factor
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ABSTRACT: Previous studies have established that higher birthweight is associated with increased risk of breast cancer. However, the mechanisms underlying this association remain unclear. We explored whether maternal pregnancy weight gain and pre-pregnancy body mass index (BMI), which influence birthweight, are associated with risk of breast cancer in offspring. The Nurses' Mothers case-control study of breast cancer was nested in the Nurses' Health Study I and II cohorts. Mothers of 814 nurses with and 1,809 nurses without breast cancer completed questionnaires with information on pre-pregnancy height and weight, pregnancy weight gain, and other aspects of their pregnancies with the nurse daughters. We calculated odds ratios for breast cancer using conditional logistic regression. Mean pregnancy weight gain was 23 lb, and average pre-pregnancy BMI was 21 kg/m². Mothers' weight gain during pregnancy was not associated with the daughters' risk of breast cancer. Compared to women whose mothers gained 20-29 lb, women whose mothers gained less than 10 lb had a relative risk of 0.92 (95% confidence interval [CI]: 0.62-1.36), adjusting for the age of the nurses. Women whose mothers gained 40 or more pounds had a relative risk of 0.82 (95% CI: 0.55-1.23). Mothers' pre-pregnancy BMI was not associated with the daughters' risk of breast cancer. Women whose mothers had a pre-pregnancy BMI of 30 or more had a relative risk of 0.77 (95% CI: 0.34-1.74) compared to those with BMI less than 20. Additional adjustment for prenatal factors or for nurses' characteristics later in life had no effect on the results. The association between birthweight and breast cancer risk is likely due to factors independent of mothers' weight gain during pregnancy or pre-pregnancy BMI. Because BMIs and pregnancy weight gains were lower in this population than today, we cannot rule out associations for very high pre-pregnancy BMIs or pregnancy weight gains.
Breast Cancer Research and Treatment 05/2011; 130(1):273-9. · 4.43 Impact Factor
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ABSTRACT: Overweight and obesity are inversely related to the risk of breast cancer among premenopausal women. We assessed the association between adult weight change since age 18 years with the risk of breast cancer among premenopausal women to explore whether weight gain was associated with a decrease in risk and weight loss was associated with an increase in risk. A total of 56,223 premenopausal participants in the Nurses' Health Study and 109,385 premenopausal participants in the Nurses' Health Study II were prospectively followed for up to 32 years and 18 years, respectively, and weight change since age 18 years was assessed biennially. The incidence of invasive breast cancer was assessed throughout follow-up. Weight loss of 5 kg or more since age 18, maintained for at least 4 years, was related to lower incidence of premenopausal breast cancer, compared to maintaining a stable weight, but this relation was of borderline statistical significance (covariate-adjusted HR = 0.75; 95% CI 0.52-1.09). Weight gain since age 18 years was also inversely related to breast cancer incidence among premenopausal women (covariate-adjusted p for trend = 0.01), but the association weakened after controlling for weight at age 18 and did not reach statistical significance (p for trend = 0.08). Although obesity and breast cancer among premenopausal women are inversely related, weight loss since age 18 years did not increase and weight gain did not significantly decrease the risk of premenopausal breast cancer among participants in the large prospective cohorts of NHS and NHS II.
International Journal of Cancer 03/2011; 130(4):902-9. · 5.44 Impact Factor
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ABSTRACT: Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer. We investigated the association between body fat distribution, assessed in 1993 by self-reported waist circumference, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses' Health Study II. Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). Statistical tests were two-sided. During 426,164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45,799 women. Hormone receptor status information was available for 84% of the breast cancers. The age-standardized incidence rates of breast cancer were 131 per 100,000 person-years among those in the lowest quintile of waist circumference and 136 per 100,000 person-years among those in the highest quintile. No statistically significant associations were found between waist circumference, hip circumference, or the waist to hip ratio and risk of breast cancer. However, each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)-negative breast cancer. The multivariable-adjusted hazard ratios of ER-negative breast cancer for the highest vs the lowest quintile of each body fat distribution measure were 2.75 (95% CI = 1.15 to 6.54; P(trend) = .05) for waist circumference, 2.40 (95% CI = 0.95 to 6.08; P(trend) = .26) for hip circumference, and 1.95 (95% CI = 1.10 to 3.46; P(trend) = .01) for waist to hip ratio. Our findings suggest that body fat distribution does not play an important role in the overall incidence of premenopausal breast cancer but is associated with an increased risk for ER-negative breast cancer.
CancerSpectrum Knowledge Environment 02/2011; 103(3):273-8. · 14.07 Impact Factor
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ABSTRACT: Tobacco smoke contains carcinogens, which may increase the risk of breast cancer (BC). Conversely, cigarette smoking also has antiestrogenic effects, which may reduce the risk of BC. The association between smoking and BC remains controversial.
Prospective cohort study of 111 140 participants of the Nurses' Health Study from 1976 to 2006 for active smoking and 36 017 women from 1982 to 2006 for passive smoking.
During 3 005 863 person-years of follow-up, 8772 incident cases of invasive BC were reported. After adjustment for potential confounders, the hazard ratio (HR) of BC was 1.06% (95% confidence interval [CI], 1.01%-1.10%) for ever smokers relative to never smokers. Breast cancer incidence was associated with a higher quantity of current (P for trend = .02) and past (P for trend = .003) smoking, younger age at smoking initiation (P for trend = .01), longer duration of smoking (P for trend = .01), and more pack-years of smoking (P for trend = .005). Premenopausal smoking was associated with a slightly higher incidence of BC (HR, 1.11; 95% CI, 1.07-1.15 for every increase of 20 pack-years), especially smoking before first birth (1.18; 1.10-1.27 for every increase of 20 pack-years). Conversely, the direction of the association between postmenopausal smoking and BC was inverse (0.93; 0.85-1.02 for every increase of 20 pack-years). Passive smoking in childhood or adulthood was not associated with BC risk.
Active smoking, especially smoking before the first birth, may be associated with a modest increase in the risk of BC.
Archives of internal medicine 01/2011; 171(2):125-33. · 11.46 Impact Factor
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ABSTRACT: Low birthweight, premature birth, intrauterine growth retardation, and maternal malnutrition have been related to an increased risk of cardiovascular disease, type 2 diabetes mellitus, obesity, and neuropsychiatric disorders later in life. Conversely, high birthweight has been linked to future risk of cancer. Global DNA methylation estimated by the methylation of repetitive sequences in the genome is an indicator of susceptibility to chronic diseases. We used data and biospecimens from an epigenetic birth cohort to explore the association between trajectories of fetal and maternal weight and LINE-1 methylation in 319 mother-child dyads. Newborns with low or high birthweight had significantly lower LINE-1 methylation levels in their cord blood compared to normal weight infants after adjusting for gestational age, sex of the child, maternal age at delivery, and maternal smoking during pregnancy (p = 0.007 and p = 0.036, respectively), but the magnitude of the difference was small. Infants born prematurely also had lower LINE-1 methylation levels in cord blood compared to term infants, and this difference, though small, was statistically significant (p = 0.004). We did not find important associations between maternal prepregnancy BMI or gestational weight gain and global methylation of the cord blood or fetal placental tissue. In conclusion, we found significant differences in cord blood LINE-1 methylation among newborns with low and high birthweight as well as among prematurely born infants. Future studies may elucidate whether chromosomal instabilities or other functional consequences of these changes contribute to the increased risk of chronic diseases among individuals with these characteristics.
PLoS ONE 01/2011; 6(9):e25254. · 4.09 Impact Factor
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ABSTRACT: Breast cancer is the most common female cancer worldwide and the second leading cause of cancer death (after lung cancer)
(American Cancer Society 2009). The incidence of breast cancer varies four- to fivefold across countries, is the highest in
Europe and North America, and the lowest in Asia (Ferlay et al. 2001). Breast cancer incidence has been on the rise since
the 1930s, with more dramatic increase in the 1980s (White et al. 1990; Devesa et al. 1994). The incidence of breast cancer
in the US stabilized from 2001 to 2003 and started to decline in 2003, possibly due, in part, to the reduced use of hormone
replacement therapy (Howe et al. 2006). It was projected that in 2010, 207,090 women would develop invasive breast cancer
and 39,840 women will die from the disease (American Cancer Society 2010).
11/2010: pages 39-52;
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ABSTRACT: The effect of caffeine intake during pregnancy on the risk of preterm delivery has been studied for the past 3 decades with inconsistent results.
We performed a meta-analysis examining the association between caffeine consumption during pregnancy and risk of preterm birth.
We searched MEDLINE and EMBASE articles published between 1966 and July 2010, cross-referenced reference lists of the retrieved articles, and identified 15 cohort and 7 case-control studies that met inclusion criteria for this meta-analysis.
The combined odds ratios (ORs) obtained by using fixed-effects models for cohort studies were 1.11 (95% CI: 0.96, 1.28), 1.10 (95% CI: 1.01, 1.19), and 1.08 (95% CI: 0.93, 1.27) for risk of preterm birth comparing the highest with the lowest level of caffeine intake (or no intake) (mg/d) during the first, second, and third trimesters, respectively. Results for the case-control studies yielded no associations for the first (OR: 1.07; 95% CI: 0.84, 1.37), second (OR: 1.17; 95% CI: 0.94, 1.45), or third (OR: 0.94; 95% CI: 0.79, 1.12) trimesters. No overall heterogeneity was found by region, publication decade, exposure and outcome assessment, caffeine sources, or adjustment for confounding, which was largely driven by individual studies.
In this meta-analysis, we observed no important association between caffeine intake during pregnancy and the risk of preterm birth for cohort and case-control studies.
American Journal of Clinical Nutrition 11/2010; 92(5):1120-32. · 6.67 Impact Factor
