Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

PurposeBRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigatedfor the first time to our knowledgeassociations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction.Materials and MethodsWe genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights.ResultsIn male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 x 10(-6)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 x 10(-9)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively.ConclusionPRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.Peer reviewe

Uncommon disorders and decay in near-isogenic lines of melon and reference cultivars Acidentes fisiológicos e podridões atípicas em linhas quase-isogénicas de melão e em cultivares de referência

Postharvest disorders and rots can produce important economic losses in fruits stored for long time for exportation. The genetic and physiological basis of some disorders in melon (Cucumis melo L.) are unknown and particularly the possible relation with climacteric behavior. A collection of melon near-isogenic lines (NILs) (SC3-5 and seven more showing climacteric and two non-climacteric ripening pattern) were analyzed to study genetic and physiological aspects of fruit disorders and rots. Two non-climacteric (Nicolás; Inodorus Group; and Shongwan Charmi PI161375, Conomon Group) and two climacteric cultivars (Fado, Reticulatus Group; Védrantais, Cantaloupensis Group) were used as reference. The field was divided in eight blocks containing one three-plant replication for each NIL, two for the parental cultivar Piel de Sapo and one or two for the reference cultivars. Replications evaluated were more than six in the cultivars studied. Plant problems included aphids, powdery mildew, and leaf wind injury. Preharvest fruit disorders included whole fruit cracking in cultivar Védrantais and NIL 5M2, and stylar-end cracking in cultivar Fado. Climacteric NILs with yellow skin were particularly affected by over-ripening, stylar-end cracking, and sunburn during cultivation. At harvest, two NILs showed slight placental tissue necrosis which was inherited from SC and were also detected after storage. Other uncommon disorders seen at harvest or 30 days after storage at 8ºC included warted skin (scarring), flesh discoloration (light brown or translucent areas), hollow flesh disorder, and deep furrow netting inherited from SC. Less common rots included grey mould, bacterial soft rot, Penicillium rot, cottony leak and internal Cladosporium rot. Stylar-end hardness below 20 N·mm-1 was associated with cracking and softening. The incidence of the disorders and rots was too low to confirm that the genetic component played a role in their development.<br>Analisaram-se frutos de melão (Cucumis melo L.) provenientes de uma coleção de linhas quase-isogénicas (NIL), SC3-5 e outras sete climatéricas e duas não-climatéricas, para avaliar a ocorrência de acidentes fisiológicos e a suscetibilidade a podridões. Como termo de comparação utilizou-se duas cultivares não-climatéricas (Nicolás, grupo Inodorus, e Shongwan Charmi ou acesso PI161375, grupo Conomon) e duas cultivares climatéricas (Fado, grupo Reticulatus, e Védrantais, grupo Cantaloupensis). O experimento foi dividido em oito blocos contendo três plantas por repetição para NIL, dois para a cultivar parental Piel de Sapo (PS), e um ou dois para a cultivar testemunha. As repetições avaliadas foram mais de seis para as cultivares em estudo. Durante a produção, as folhas foram afetadas por pulgão, oídio e acidentes meteorológicos. Os acidentes fisiológicos que ocorreram nos frutos durante a produção incluíram fendilhamento na cultivar Védrantais e na NIL 5M2 e fendilhamento da zona pistilar na cultivar Fado. As NIL climactéricas com casca amarela revelaram-se muito suscetíveis à sobre-maturação, fendilhamento pistilar e queimaduras solares durante a produção. Duas NIL exibiram uma ligeira necrose do tecido placentar, carater herdado da linha PI161375. Outros acidentes fisiológicos atípicos observados na colheita ou após 30 dias a 8ºC incluíram casca verrugosa, descolorações castanho-claras na polpa, translucência da polpa, cavidades na polpa e ornamentação profundamente sulcada na casca, herdada do PI161375. Observou-se a ocorrência de podridões pouco usuais em melão, nomeadamente podridão cinzenta, podridão bacteriana, Penicillium sp., Phytium sp. e cladosporiose interna. Uma dureza da região pistilar inferior a 20 N mm-1 estava associada ao fendilhamento e ao amolecimento excessivo. A ocorrência destes acidentes fisiológicos ou podridões foi baixa para assegurar o envolvimento de fatores genéticos no seu desenvolvimento

Primary structure of the N-linked carbohydrate chains of calreticulin from spinach leaves

Calreticulin is a multifunctional Ca2+-binding protein of the endoplasmic reticulum of most eukaryotic cells. The 56 kDa Calreticulin glycoprotein isolated from spinach (Spinacia oleracea L.) leaves was N-deglycosylated by PNGase-F digestion. The carbohydrate moiety was isolated by gel permeation chromatography and purified by high-pH anion-exchange chromatography. The fractions were investigated by 500 MHz H-1-NMR spectroscopy, in combination with monosaccharide analysis and fast-atom bombardment-mass spectrometry. The following carbohydrate structure could be established as the major component (Man(8)GlcNAc(2)): [GRAPHICS] Heterogeneity was demonstrated by the presence of two minor components being Man(7)GlcNAc(2) lacking a terminal residue (D-1 or D-3), compared to the major component. A. cross-reactivity with an antibody against the endoplasmic reticulum retention signal HDEL was also found

Predicting ground reaction forces in running using micro-sensors and neural networks

Abstract not available