Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Lipids are required for directional pollen-tube growth

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Relationship between grain colour and preharvest sprouting-resistance in wheat Relação entre cor de grão e resistência à germinação pré-colheita em trigo

Since red alleles (R) of the genes that control grain colour are important for the improvement of preharvest sprouting resistance in wheat and there are three independently inherited loci, on chromosomes 3A, 3B and 3D of hexaploid wheat, it is possible to vary the dosage of dominant alleles in a breeding program. The objective of this work was to evaluate the dosage effect of R genes on preharvest sprouting, in a single seed descent population, named TRL, derived from the cross between Timgalen, white-grained wheat, and RL 4137, red-grained wheat. The study was carried out using sprouting data in ripe ears obtained under artificial conditions in a rainfall simulator over three years. According to the results there is a significant effect on preharvest sprouting provided by colour and a weaker effect of increasing R dosage. However, the significant residual genotypic variation between red lines and all lines (reds and whites) at 0.1% level showed that preharvest sprouting was also controlled by other genes. There are no significant correlations between sprouting and date of ripeness or between ripeness, R dosage and colour intensity.<br>Uma vez que os alelos dominantes para cor vermelha (R), dos genes que controlam a cor do grão, têm importância no incremento da resistência à germinação pré-colheita, em trigo, e há três locos herdados independentemente, nos cromossomos 3A, 3B e 3D do trigo hexaplóide, é possível variar sua dosagem em um programa de melhoramento. O objetivo deste trabalho foi avaliar o efeito de dosagem dos genes R na germinação pré-colheita, em uma população de descendência por semente única, batizada de TRL, derivada do cruzamento entre Timgalen, trigo de grão branco, e RL 4137, trigo de grão vermelho. O estudo utilizou dados de germinação em espigas maduras, obtidos sob condições artificiais em um simulador de chuva, em três anos. De acordo com os resultados, o efeito da cor de grão e, menos acentuadamente, da dosagem dos alelos dominantes, sobre a germinação pré-colheita foi significativo. Entretanto, a variação genotípica residual, entre as linhas vermelhas e entre as linhas vermelhas e brancas, significativa a 0,1%, mostra que a germinação pré-colheita é também controlada por outros genes. Não foi constatada correlação significativa entre germinação na espiga e data de maturação ou entre maturação, dosagem de R e intensidade de cor