The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis

Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 women of diverse ancestries (African, Hispanic/Latina, Asian American and American Indian/Alaskan Native) in the Population Architecture using Genomics and Epidemiology (PAGE) Study were included in cross-sectional analyses of AAM and ANM. Within each study we conducted a linear regression of SNP associations with self-reported or medical record-derived AAM or ANM (in years), adjusting for birth year, population stratification, and center/region, as appropriate, and meta-analyzed results across studies using multiple meta-analytic techniques. For both AAM and ANM, we observed more directionally consistent associations with the previously reported risk alleles than expected by chance (p-valuesbinomial0.01). Eight densely genotyped reproductive loci generalized significantly to at least one non-European population. We identified one trans-ethnic array-wide SNP association with AAM and two significant associations with ANM, which have not been described previously. Additionally, we observed evidence of independent secondary signals at three of six AAM trans-ethnic loci. Our findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci. These findings suggest the benefit of including diverse populations in future studies of the genetic architecture of female growth and development

Foraminifera and microfacies of the type-Priabonian

The Priabonian is generally recognized and accepted as a stage name for the uppermost Eocene. The name is derived from the small village ofPriabona in the North Italian province of Vicenza (fig. 1). Since the underlying and overlying stages of the idealized chronostratigraphic scale are based on sections in completely different sedimentation areas in northwest Europe which are remote from each other and from Priabona, the correlation between the type sections, especially at the Eocene-Oligocene boundary has been a subject of much discussion. The predominantly carbonate facies of the Priabonian deposits contain abundant larger foraminifera, and were therefore of great interest to paleontologists at the beginning of the 20th century. Unfortunately the groups represented belong to poorly defined lineages without distinct or sufficiently well-known evolutionary trends. In addition, the scarcity of planktonic organisms means that the type Priabonian is not very promising as a basis for establishing modern biostratigraphic correlations. The primary object of this study is to provide an illustrated record of the smaller foraminifera, both benthonic and planktonic. The widest possible range of habitats was obtained by investigating the contents of three sections: the Buco della Rana section, thought to lie close to the Late Eocene shallow carbonate platform; the off-shore Bressana section; and the Priabona section, paleogeographically situated in an intermediate position on the slope between platform and off-shore area. An additional study has been carried out involving microfacies analysis of the carbonates ~nd quantitative investigations of the benthonic faunas from intercalated marls. The purpose of this study was to obtain a better appreciation of the environments of the deposition and a correct biostratigraphic correlation of the three sections. The original intention was to give a thorough account of biometrical data on the larger foraminifera, but this had to be restricted to a detailed study of certain assemblages of the Discocydinidae

The etiology of uterine sarcomas: A pooled analysis of the epidemiology of endometrial cancer consortium

Background: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. Methods: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28 829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. Results: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m-2 (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). Conclusion: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age-and race-specific incidence rates for uterine sarcoma are needed. © 2013 Cancer Research UK. All rights reserved

Pregnancy Outcomes and Risk of Endometrial Cancer: A Pooled Analysis of Individual Participant Data in the Epidemiology of Endometrial Cancer Consortium

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16,986 women with endometrial cancer and 39,538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (OR) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR=0.59, 95% confidence interval (CI) 0.56-0.63). The risk reduction appeared greatest for the first full-term pregnancy (OR=0.78, 95%CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR=0.20, 95%CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy

Understanding risk factors for endometrial cancer in young women.

The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet &lt; .01). Body mass index was the strongest risk factor (OR≥35 vs&lt;25 kg/m2 = 5.57, 95% CI = 4.33 to 7.16, for ages younger than 50 years; OR≥35 vs&lt;25 kg/m2 = 4.68, 95% CI = 4.30 to 5.09, for ages 50 years and older; Phet = .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet &lt; .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women

Coralline algal facies and their palaeoenvironments in the Late Eocene of Northern Italy (Calcare di Nago, Trento)

The Calcare di Nago is a carbonate unit of Middle- Late Eocene (Bartonian and Priabonian) age which is well exposed at the north-eastern end of Lake Garda, on the western margin of the Lessini Shelf (Southern Alps). This unit is highly fossiliferous as far as the coralline red algae and large foraminifera are concerned. Corals, bryozoans, echinoderms, and molluscs are also present. The present study deals with the relationships among the coralline taxa, the coralline growth-forms, and their facies development in the Priabonian part of the type section of the Calcare di Nago. The taxonomic investigation led to the identification of 15 coralline red algal species belonging to 7 non-geniculate and 2 geniculate genera. One species of Peyssonneliacean (red alga) and one of Halimedacean (green alga) were also recognized. The quantitative and qualitative analyses based on coralline red algae and large foraminifera enabled five facies to be distinguished: Algal crust-branch rudstone, AlgallDiscocyclina packstone, Coralalgal boundstone, Rhodolith mound wacke/packstone, and Rhodolith pavement. According to the coralline assemblages, coralline growth-forms, and large foraminiferal associations, the five facies reflect solid and soft substrate types. Some of these facies are dominated by in situ rhodoliths, others by reworked algal debris. In the architecture of an interpreted prograding carbonate ramp, shallow water facies are dominated by members of the subfamily Mastophoroideae, while deeper water facies are dominated by those of the subfamily Melobesioideae and family Sporolithaceae. There is a significant increase both in size and in constructional voids of the rhodoliths with depth. A concomitant decrease in algal species diversity with depth has been also recognized. Large Discocyclina assemblages are localized across the inner and mid ramp boundary. Pellatispira and Biplanispira are present only in the uppermost mid-ramp. Nummulites, Assilina, and Spiroclypeus are dominant together with small orthophragminids both in the mid- and uppermost outer ramp facies