Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States

Although the association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma of the cervix and vagina (CCA) was first reported among young women, subsequent case reports and cohort studies suggest that an elevated risk for CCA may persist with age. Data from the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program were used to construct indirect standardized incidence ratios (SIR) comparing CCA risk among women born during the exposure period 1947 through 1971, when DES was prescribed to pregnant women, to the relevant time period for nonexposed women born before or after DES exposure period. CCA incidence among the women born before the DES exposure period (ages 30–54 at diagnosis of CAA) or after the DES exposure period (ages 15–29 at diagnosis) were used to calculate the expected rates for women born during the DES exposure period. Among women aged 15–29 years, CCA risk increased with age and peaked in the 25–29 year age group, but the risk estimates were unstable (SIR = 6.06; 95% CI: 0.97, −251.07, SEER data). Among women aged 40–54 years, CCA risk was greatest in the 40–44 year age group (SIR = 4.55; 95% CI: 1.11, 40.19, SEER data and SIR = 3.94; 95% CI: 1.06, 33.01, NPCR/SEER data) and remained significantly elevated throughout this age group in the combined data set. Risk was not elevated among women aged 30–39 years. The observed risk of CCA, if causally related to DES exposure, reflects a persistent health impact from in utero exposure that is widespread in the general population. When assessing a woman’s cancer risks, whether her mother took DES while pregnant may still be a relevant aspect of the medical history for women born during the period of DES use in pregnancy

Influence of Prenatal Arsenic Exposure and Newborn Sex on Global Methylation of Cord Blood DNA

Background An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. Objective The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. Design Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs). Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. Results In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1) and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58) but negative among female newborns (N = 43); tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively) and for the association between maternal uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p\u3c0.05). Conclusions These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm these findings and to examine the persistence of DNA methylation marks over time

Cancer risk in DES daughters

We examined long-term risk of cancer in women exposed to diethylstilbestrol (DES) in utero. A total of 12,091 DES-exposed women in the Netherlands were followed prospectively from December 1992 till June 2008. Cancer incidence was assessed through linkage with the Dutch pathology database (PALGA) and the Netherlands Cancer Registry and compared with the Dutch female population. A total of 348 medically verified cancers occurred; median age at end of follow-up was 44.0 years. No overall increased risk of cancer was found (standardized incidence ratio [SIR] = 1.01; 95% confidence interval [CI] = 0.91, 1.13). The risk of clear cell adenocarcinoma of the vagina and cervix (CCA) was statistically significantly increased (SIR = 24.23; 95% CI = 8.89, 52.74); the elevated risk persisted above 40 years of age. The risk of melanoma diagnosed before age 40 was increased (SIR = 1.59; 95% CI = 1.08, 2.26). No excess risks were found for other sites, including breast cancer. Except for an elevated risk of CCA, persisting at older ages, and an increased risk of melanoma at young ages, we found no increased risk of cancer. Longer follow-up is warranted to examine cancer risk at ages when cancer occurs more frequently

Pregnancy weight gain and breast cancer risk

BACKGROUND: Elevated pregnancy estrogen levels are associated with increased risk of developing breast cancer in mothers. We studied whether pregnancy weight gain that has been linked to high circulating estrogen levels, affects a mother's breast cancer risk. METHODS: Our cohort consisted of women who were pregnant between 1954–1963 in Helsinki, Finland, 2,089 of which were eligible for the study. Pregnancy data were collected from patient records of maternity centers. 123 subsequent breast cancer cases were identified through a record linkage to the Finnish Cancer Registry, and the mean age at diagnosis was 56 years (range 35 – 74). A sample of 979 women (123 cases, 856 controls) from the cohort was linked to the Hospital Inpatient Registry to obtain information on the women's stay in hospitals. RESULTS: Mothers in the upper tertile of pregnancy weight gain (>15 kg) had a 1.62-fold (95% CI 1.03–2.53) higher breast cancer risk than mothers who gained the recommended amount (the middle tertile, mean: 12.9 kg, range 11–15 kg), after adjusting for mother's age at menarche, age at first birth, age at index pregnancy, parity at the index birth, and body mass index (BMI) before the index pregnancy. In a separate nested case-control study (n = 65 cases and 431 controls), adjustment for BMI at the time of breast cancer diagnosis did not modify the findings. CONCLUSIONS: Our study suggests that high pregnancy weight gain increases later breast cancer risk, independently from body weight at the time of diagnosis

Heart Rate during Conflicts Predicts Post-Conflict Stress-Related Behavior in Greylag Geese

Background: Social stressors are known to be among the most potent stressors in group-living animals. This is not only manifested in individual physiology (heart rate, glucocorticoids), but also in how individuals behave directly after a conflict. Certain ‘stress-related behaviors ’ such as autopreening, body shaking, scratching and vigilance have been suggested to indicate an individual’s emotional state. Such behaviors may also alleviate stress, but the behavioral context and physiological basis of those behaviors is still poorly understood. Methodology/Principal Findings: We recorded beat-to-beat heart rates (HR) of 22 greylag geese in response to agonistic encounters using fully implanted sensor-transmitter packages. Additionally, for 143 major events we analyzed the behavior shown by our focal animals in the first two minutes after an interaction. Our results show that the HR during encounters and characteristics of the interaction predicted the frequency and duration of behaviors shown after a conflict. Conclusions/Significance: To our knowledge this is the first study to quantify the physiological and behavioral responses to single agonistic encounters and to link this to post conflict behavior. Our results demonstrate that ‘stress-related behaviors’ are flexibly modulated by the characteristics of the preceding aggressive interaction and reflect the individual’s emotional strain, which is linked to autonomic arousal. We found no support for the stress-alleviating hypothesis, but we propose tha

Intrauterine environments and breast cancer risk: meta-analysis and systematic review

INTRODUCTION: Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS: We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS: We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION: Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood

Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes

We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains—Dominance, Sociability, and Neuroticism—were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans

Obstetric history and mammographic density: a population-based cross-sectional study in Spain (DDM-Spain)

High mammographic density (MD) is used as a phenotype risk marker for developing breast cancer. During pregnancy and lactation the breast attains full development, with a cellular-proliferation followed by a lobular-differentiation stage. This study investigates the influence of obstetric factors on MD among pre- and post-menopausal women. We enrolled 3,574 women aged 45–68 years who were participating in breast cancer screening programmes in seven screening centers. To measure MD, blind anonymous readings were taken by an experienced radiologist, using craniocaudal mammography and Boyd’s semiquantitative scale. Demographic and reproductive data were directly surveyed by purpose-trained staff at the date of screening. The association between MD and obstetric variables was quantified by ordinal logistic regression, with screening centre introduced as a random effect term. We adjusted for age, number of children and body mass index, and stratified by menopausal status. Parity was inversely associated with density, the probability of having high MD decreased by 16% for each new birth (P value < 0.001). Among parous women, a positive association was detected with duration of lactation [>9 months: odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.02–1.72] and weight of first child (>3,500 g: OR = 1.32; 95% CI = 1.12–1.54). Age at first birth showed a different effect in pre- and post-menopausal women (P value for interaction = 0.030). No association was found among pre-menopausal women. However, in post-menopausal women the probability of having high MD increased in women who had their first child after the age of 30 (OR = 1.53; 95% CI = 1.17–2.00). A higher risk associated with birth of twins was also mainly observed in post-menopausal women (OR = 2.02; 95% CI = 1.18–3.46). Our study shows a greater prevalence of high MD in mothers of advanced age at first birth, those who had twins, those who have breastfed for longer periods, and mothers whose first child had an elevated birth weight. These results suggest the influence of hormones and growth factors over the proliferative activity of the mammary gland