Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

A survey of semen donor attitudes

Semen donors have been required to register with the Human Fertilization and Embryology Authority since its formation in 1990. Since then many clinics have reported a shortage of donor semen for donor insemination treatment. Is this because potential donors are worried about the protection of their anonymity? No published studies are available concerning the attitudes to semen donation in the UK. It was against this background that an investigation of the attitudes of potential semen donors was carried out. Four dimensions were investigated: (i) motives, (ii) personal detachment and involvement, (iii) detachment and involvement with respect to recipients, and (iv) detachment and involvement with respect to offspring. A total of 55 potential semen donors completed the attitude questionnaire from semen donation programmes in three in-vitro fertilization units. The questionnaire format was found to be an effective method of data collection for this sensitive area of research, and the major findings were (i) 89% of potential donors required confidentiality and guaranteed anonymity; (ii) 82% did not mind providing non-identifying information to the recipients and offspring; (iii) 69% of potential donors expected financial reward; and (iv) 69% did not welcome counselling

Single monthly administration of the anti-progestagen Org 31710 in users of the 75 microg desogestrel progestagen-only pill: effects on pituitary-ovarian activity

Endocrine and ultrasound effects were studied of an intermittent (every 28 days) oral administration of 150 mg of the anti-progestagen Org 31710 during the continued daily use of 75 microg desogestrel (DSG) for progestagen-only contraception. A randomized, double-blind, placebo-controlled two-centre study was conducted in 50 healthy volunteers. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and progesterone concentrations, and follicle number and size were studied, as well as endometrial thickness, which was assessed by transvaginal sonography at least twice weekly during a single medication cycle (cycle 3-5). Forty-eight women were evaluated (Org 31710, n = 25; placebo, n = 23). Seven ovulations were observed in the treated group versus none in the placebo group. LH concentrations were higher on days 9 and 11 and oestradiol concentrations lower on day 3 in the treated group, irrespective of whether ovulation occurred. No parameter could predict ovulation. Endometrial thickness was greater on cycle days 7-13 and 19 in the treated group. However, within the Org 31710 group, no significant differences were found in volunteers who did or did not ovulate. Observed differences may be attributed to a competitive effect of Org 31710 with progestagen-induced suppression of the pituitary-ovarian axis, altered oestradiol feedback mechanisms, and/or altered receptor availability

Physiological age in Lutzomyia youngi (Diptera: Psychodidae) populations from an endemic area for cutaneous leishmaniasis, Venezuela Edad fisiológica de poblaciones de Lutzomyia youngi (Diptera: Psychodidae) de una área endémica de leishmaniasis cutánea

Batches of sylvatic females of Lutzomyia youngi (Phlebotominae) captured in a Shannon trap on twelve occasions over one year in a locality where subcutaneous leishmaniasis is endemic, near the city of Trujillo, Venezuela, were used to study: 1) the percentages of parous females according to previously established criteria and 2) the average number of eggs laid spontaneously by isolated females during 7 days after feeding on hamsters. The data on the batches of females captured on nights previous to the rainy period (prepluvial) were compared with those on females captured after the rains (postpluvial) . Significant differences were detected by variation analysis for two variables and different number of N, as also were consistent groupings by Duncan's Test for pre-and postpluvial lots of females. The females captured on nights prior to the rainy periods (January-March and August-September) presented higher rates of nulliparity (86-72%) and contained or laid a greater number of eggs (71-67) than those captured after the rains (March-June and November-December) which presented lower rates of nulliparity (60-24%) and a smaller number of eggs (50-30). The rainfall peaks occurred in April and September-October, respectively. It is considered that these differences can be used by epidemiological studies as a means of estimating the physiological age of female populations of L. youngy.<br>Con lotes de hembras silvestres de Lutzomyia youngi (Phlebotominae) capturadas con trampa de Shannon en doce ocasiones a lo largo de un año, en una localidad endémica para leishmaniasis tegumentaria, próxima a la ciudad de Trujillo, Venezuela, se estudio: 1) los percentajes de hembras paridas según criterios previamente establecidos y 2) el número medio de huevos puestos espontaneamente por hembras aisladas, en el curso de 7 días postigestión, ingurgitadas también sobre hámsteres. Se comparó la data de lotes de hembras capturadas, en noches de días anteriores a los períodos de lluvias (prepluviales) con las de hembras capturadas después de las lluvias (postpluviales). Se detectó diferencias significativas por análisis de varianza para dos variables y diferente número de N, y también consistentes agrupaciones con la prueba de Duncan para lotes de hembras pre y postpluviales. Las hembras capturadas en noches previas a los periodos de lluvias (Enero - Marzo y Agosto - Septiembre) exhibieron más altas tasas de nuliparidad (86-72%) y contuvieron o eliminaron mayor número de huevos (71-67), que las hembras capturadas después de las lluvias (Marzo-Junio y Noviembre - Diciembre), con mas bajas tasas de nuliparidad (60-24%) y menores números de huevos (50-30). Los picos de lluvias ocurrieron en Abril y Septiembre - Octubre, respectivamente. Se considera que estas diferencias puedan ser utilizadas, como una estimativa de la edad fisiológica de problaciones de hembras de L. youngi, en estudios epidemiológicos

Variações regionais e interespecíficas na morfologia de insetos do complexo Lutzomyia intermedia (Diptera, Psychodidae, Phlebotominae) Regional and interspecific variations in the morphology of insects of the Lutzomyia intermedia complex (Diptera, Psychodidae, Phlebotominae)

INTRODUÇÃO: Lutzomyia intermedia s. s. e L. neivai, usualmente consideradas como pertencentes a uma só espécie, constituem um complexo de espécies. Foram analisadas as medidas de várias estruturas de exemplares das duas espécies, provenientes do Brasil, Paraguai, Argentina e Bolívia. MÉTODO: Foram medidas 39 estruturas em exemplares de ambos os sexos, com ocular graduada, fazendo-se comparações por análise de variância (ANOVA). RESULTADOS: Constatou-se desvio significativo nas proporções de fêmeas e de machos com cada fórmula palpal e influência da região de origem dos insetos. O labro e os palpos maxilares foram mais longos nas fêmeas e o antenômero III mais longo nos machos. Foram constatadas várias diferenças entre medidas das asas, quase todas maiores nas fêmeas. A proporção de espermatecas com cabeça simples em L. neivai é significativamente maior que em L. intermedia. Também foram observadas diferenças significativas nos comprimentos das bombas e dos dutos ejaculadores entre as espécies. DISCUSSÃO: As variações nas fórmulas palpais ressaltam o risco do uso desta fórmula para a associação entre exemplares de ambos os sexos. As diferenças nos comprimentos dos palpos e no labro podem estar ligadas à hematofagia das fêmeas. Comenta-se sobre as possíveis implicações da maior relação comprimento/largura das asas em machos. As diferenças nas proporções de fêmeas das duas espécies com os diferentes tipos de cabeça de espermatecas podem auxiliar na identificação específica. As diferenças nos comprimentos das bombas e dos dutos ejaculadores e nas relações entre estes comprimentos podem auxiliar na identificação dos machos, ainda difícil.<br>INTRODUCTION: Lutzomyia intermedia s. s. and L. neivai, usually considered as belonging to just one species, constitute a complex of species. The measurements of several anatomical structures of specimens of both groups, from Brazil, Paraguay, Argentina and Bolivia were analysed. METHOD: Thirty-nine structures were measured in specimens of both sexes, using a graduated ocular, analysing comparisons by analyses of variance (ANOVA). RESULTS: A significant deviation in the proportions of females and males showing each palpal formula and the influence of the region of origin of the flies were verified. Labrum and maxilary palps were longer in females and Antennomere III was longer of males. Several significant differences in the measurements of wings were noted, most of them greater in females. The proportion of spermathecae with simple heads was significantly greater in L. neivai than in L. intermedia. Significant differences in the length of genital pump and filaments between the species were also noted. DISCUSSION: The variation in the palpal formulae in both sexes show the risk of the use of this formula for the association between specimens of the two sexes. The differences in the lengths of palps and labrum between the sexes could be related to female blood feeding. The possible biological significance of the sexual differential relation length/width of wings is commented on. The different proportions of females of the two species with each spermathecae head shape may help in identification. The differences in the lengths of genital pumps and filaments and the relation between them could help in the identification of males, which is still difficult