Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

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

Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident

BACKGROUND: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated (131)I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear-exponential functions. RESULTS: For thyroid doses \u3c5 \u3eGy, the dose-response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation

Lifecourse socioeconomic circumstances and multimorbidity among older adults

<p>Abstract</p> <p>Background</p> <p>Many older adults manage multiple chronic conditions (i.e. multimorbidity); and many of these chronic conditions share common risk factors such as low socioeconomic status (SES) in adulthood and low SES across the lifecourse. To better capture socioeconomic condition in childhood, recent research in lifecourse epidemiology has broadened the notion of SES to include the experience of specific hardships. In this study we investigate the association among childhood financial hardship, lifetime earnings, and multimorbidity.</p> <p>Methods</p> <p>Cross-sectional analysis of 7,305 participants age 50 and older from the 2004 Health and Retirement Study (HRS) who also gave permission for their HRS records to be linked to their Social Security Records in the United States. Zero-inflated Poisson regression models were used to simultaneously model the likelihood of the absence of morbidity and the expected number of chronic conditions.</p> <p>Results</p> <p>Childhood financial hardship and lifetime earnings were not associated with the absence of morbidity. However, childhood financial hardship was associated with an 8% higher number of chronic conditions; and, an increase in lifetime earnings, operationalized as average annual earnings during young and middle adulthood, was associated with a 5% lower number of chronic conditions reported. We also found a significant interaction between childhood financial hardship and lifetime earnings on multimorbidity.</p> <p>Conclusions</p> <p>This study shows that childhood financial hardship and lifetime earnings are associated with multimorbidity, but not associated with the absence of morbidity. Lifetime earnings modified the association between childhood financial hardship and multimorbidity suggesting that this association is differentially influential depending on earnings across young and middle adulthood. Further research is needed to elucidate lifecourse socioeconomic pathways associated with the absence of morbidity and the presence of multimorbidity among older adults.</p

Fossil herbivore stable isotopes reveal middle Pleistocene hominin palaeoenvironment in ‘Green Arabia’

Despite its largely hyper-arid and inhospitable climate today, the Arabian Peninsula is emerging as an important area for investigating Pleistocene hominin dispersals. Recently, a member of our own species was found in northern Arabia dating to c. 90 ka, while stone tools and fossil finds have hinted at an earlier, Middle Pleistocene, hominin presence. However, there remain few direct insights into Pleistocene environments, and associated hominin adaptations, that accompanied the movement of populations into this region. Here, we apply stable carbon and oxygen isotope analysis to fossil mammal tooth enamel (n=21) from the Middle Pleistocene locality of Ti’s al Ghadah in Saudi Arabia associated with newly-discovered lithics and probable cutmarks. The results demonstrate productive grasslands in the interior of the Arabian Peninsula c. 300-500 ka, as well as aridity levels similar to those found in open savanna settings in eastern Africa today. The association between this palaeoenvironmental information and the earliest traces for hominin activity in this part of the world lead us to argue that Middle Pleistocene hominin dispersal into the interior of the Arabian Peninsula required no major novel adaptation

FGF2 alters expression of the pyrophosphate/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1 (C4)

Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling has been linked to the aberrant mineralization phenotype of craniosynostosis syndromes. One critical aspect of mineralization involves the elaboration and transport of pyrophosphate into the extracellular matrix with subsequent enzymatic hydrolysis into phosphate. Altered expression of the pyrophosphate elaborating factors, TNAP (tissue nonspecific alkaline phosphatase), PC-1, and ANK, downstream of FGF/FGFR signaling may provide a potential mechanism for the craniosynostosis phenotype. As an initial step toward testing this hypothesis, we confirmed that ANK mRNA is upregulated during osteoblast differentiation in culture. Subsequently, the effect of FGF2 treatment on expression of PC-1, ANK, and TNAP in the calvarial osteoblastic cell line, MC3T3E1(C4), was investigated. FGF2 specifically induced expression of PC-1 and ANK while inhibiting expression of TNAP, at both mRNA and protein levels. Concordant with these changes in gene expression, FGF2 inhibited mineralization. These results suggest that FGF/FGFR signaling may affect mineralization via changes in the elaboration and metabolism of pyrophosphate.464176318419