TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy.

BACKGROUND The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. METHODS We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. RESULTS No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. CONCLUSION This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

Abundance of Lutzomyia longipalpis in urban households as risk factor of transmission of visceral leishmaniasis

Urban occurrence of human and canine visceral leishmaniasis (VL) is linked to households with characteristics conducive to the presence of sand flies. This study proposes an ad hoc classification of households according to the environmental characteristics of receptivity to phlebotominae and an entomological study to validate the proposal. Here we describe the phlebotominae population found in intra- and peridomiciliary environments and analyse the spatiotemporal distribution of the VL vector Lutzomyia longipalpis of households receptive to VL. In the region, 153 households were classified into levels of receptivity to VL followed by entomological surveys in 40 of those properties. Kruskal-Wallis verified the relationship between the households’ classification and sand fly abundance and Kernel analysis evaluated L. longipalpis spatial distribution: of the 740 sand flies were captured, 91% were L. longipalpis; 82% were found peridomiciliary whilst the remaining 18% were found intradomiciliary. No statistically significant association was found between sandflies and households levels. L. longipalpis counts were concentrated in areas of high vulnerability and some specific households were responsible for the persistence of the infestation. L. longipalpis prevails over other sand fly species for urban VL transmission. The entomological study may help target the surveillance and vector control strategies to domiciles initiating and/or maintaining VL outbreaks.

Domains of p85cdc10 required for function of the fission yeast DSC-1 factor.

p85cdc10 is a component of the S.pombe DSC-1 complex, which is thought to mediate periodic transcription of genes in late G1. In order to understand the role of p85cdc10 in the function of this complex, we have analysed which domains of p85cdc10 are required for biological activity and the formation of a stable DSC-1 complex in vitro, both in cdc10 temperature sensitive and null backgrounds. No DSC-1 activity is found in the absence of p85cdc10 and the activity of the complex is reduced or absent in all cdc10ts mutants tested. Full biological activity and rescue of a cdc10::ura4+ null allele requires the N-terminal domain, the cdc10/SWI6 repeats and the helical C-terminal region. In the absence of p85cdc10, both the C-terminal and cdc10/SWI6 repeat domains are required for DSC-1 activity in vitro. In a cdc10ts background, rescue of DSC-1 activity and complementation of mutants, requires only expression of the C-terminal domain, though the presence of the cdc10/SWI6 motifs enhances its activity. The N-terminal domain, alone, or in combination with the cdc10/SWI6 motifs, does not have biological activity, and does not restore DSC-1 activity. We conclude that both the C-terminal domain of p85cdc10 is critical for formation of the DSC-1 complex and that the cdc10/SWI6 motifs also play a role, perhaps by stabilizing the complex. Our data also suggest that the S.pombe DSC-1 complex contains more than one molecule of p85cdc10.

Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene.

Fasting is associated with significant changes in nutrient metabolism, many of which are governed by transcription factors that regulate the expression of rate-limiting enzymes. One factor that plays an important role in the metabolic response to fasting is the peroxisome proliferator-activated receptor alpha (PPARalpha). To gain more insight into the role of PPARalpha during fasting, and into the regulation of metabolism during fasting in general, a search for unknown PPARalpha target genes was performed. Using subtractive hybridization (SABRE) comparing liver mRNA from wild-type and PPARalpha null mice, we isolated a novel PPARalpha target gene, encoding the secreted protein FIAF (for fasting induced adipose factor), that belongs to the family of fibrinogen/angiopoietin-like proteins. FIAF is predominantly expressed in adipose tissue and is strongly up-regulated by fasting in white adipose tissue and liver. Moreover, FIAF mRNA is decreased in white adipose tissue of PPARgamma +/- mice. FIAF protein can be detected in various tissues and in blood plasma, suggesting that FIAF has an endocrine function. Its plasma abundance is increased by fasting and decreased by chronic high fat feeding. The data suggest that FIAF represents a novel endocrine signal involved in the regulation of metabolism, especially under fasting conditions.

Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation.

Hepatitis C virus (HCV) infection induces a state of oxidative stress by affecting mitochondrial-respiratory-chain activity. By using cell lines inducibly expressing different HCV constructs, we showed previously that viral-protein expression leads to severe impairment of mitochondrial oxidative phosphorylation and to major reliance on nonoxidative glucose metabolism. However, the bioenergetic competence of the induced cells was not compromised, indicating an efficient prosurvival adaptive response. Here, we show that HCV protein expression activates hypoxia-inducible factor 1 (HIF-1) by normoxic stabilization of its alpha subunit. In consequence, expression of HIF-controlled genes, including those coding for glycolytic enzymes, was significantly upregulated. Similar expression of HIF-controlled genes was observed in cell lines inducibly expressing subgenomic HCV constructs encoding either structural or nonstructural viral proteins. Stabilization and transcriptional activation of HIF-1alpha was confirmed in Huh-7.5 cells harboring cell culture-derived infectious HCV and in liver biopsy specimens from patients with chronic hepatitis C. The HCV-related HIF-1alpha stabilization was insensitive to antioxidant treatment. Mimicking an impairment of mitochondrial oxidative phosphorylation by treatment of inducible cell lines with oligomycin resulted in stabilization of HIF-1alpha. Similar results were obtained by treatment with pyruvate, indicating that accumulation of intermediate metabolites is sufficient to stabilize HIF-1alpha. These observations provide new insights into the pathogenesis of chronic hepatitis C and, possibly, the HCV-related development of hepatocellular carcinoma.

Gregorius IX, papa, Decretales, libri I-II.

Cet exemplaire de la Lectura d’Henri de Suso sur les Décrétales, dont il ne reste que le premier volume, présente la particularité de contenir aussi le texte des Décrétales, chacune d’elles étant suivie par le commentaire correspondant. Certaines anomalies de la copie permettent de préciser que les copistes avaient comme modèle deux manuscrits différents, un pour la Lectura et l’autre pour les Décrétales dans une édition augmentée des Novelles d'Innocent IV, qui devaient être insérées à la suite des titres correspondants, selon la prescription pontificale de 1245. Le texte même des Novelles qui n’était pas commenté dans la Lectura n’a pas été repris dans la copie, sauf l’Extravagante Quia frequenter, au f. 37v, et Sext. I, 13, 1, au f. 133. F. 1-360v. F. 1-177v. "Apparatus [HENRICI de SEGUSIO cardinalis] Ostiensis super textum Decretalium". [Prooemium:] "[A]d Dei omnipotentis gloriam et universalis ecclesie decus et decorem necnon rei publice et maxime scolasticorum utilitatem... - ...emendate"; — [In epistola dedicatoria Gregorii IX:] "Vicarius regis pacifici ad communem utilitatem et maxime studencium quinque compilationes... - ...et punit" (éd.Venise, I, 3-3v). — "Incipit liber primus Decretalium". [GREGORIUS IX papa, Epistola dedicatoria, salutatio] ; suivi de [HENRICUS DE SEGUSIO, Lectura :] "Gregorius episcopus. Omnes sunt episcopi licet vocentur archiepiscopi, primates vel patriarche... de manu apud eum"; — [GREGORIUS IX papa, Epistola dedicatoria] terminée par l'inscription rubriquée de la première Décrétale; suivi de: [HENRICUS DE SEGUSIO, Lectura in epistola dedicatoria :] "Rex. Regum et omnium potestatum. VIII di. que contra mores... - ...super verbo hac tantum"; et de [ID., Lectura in prima rubrica : ]"Quoniam omne quod non est in fine... - ...de fide catholica" (éd.Venise, I, 3v-5) (1-2v). — Extra 1, 1, 1 ; suivi de [ID., Lectura : ] "Firmiter credimus. Bene dicit nam dubius in fine... - ...Extra 1, 37, 1 ; suivi de [ID., Lectura : ] "Clerici... Et si beneficio etc. careant... de foro compe.", incomplet de la fin par lacune matérielle (éd.Venise, I, 5-182, § 10) (2v-177v). A noter: var. de plusieurs lignes à l'explicit des commentaires sur Extra 1, 1, 2 et 1, 3, 11. A noter les anomalies suivantes :L’inscription de chaque Décrétale, à quelques exceptions près, a été inscrite à la fin du texte de la Décrétale précédente. Le libellé: "Innocentius IIIIus" ou bien "Innocentius IIIIus in concil. Lugdun", qui a été inscrit à la fin des titres I, 3 (25v), 6, (85), 10 (103), 28 (132v), 29 (153), 30 (155v), 31 (164) correspond, en fait, à l'inscription des Novelles d'Innocent IV éditées dans le Sexte, livre I, en tête des titres 3, 6, 8, 13, 14, 15, 16.Au f. 37v, à la suite d'Extra 1, 6, 6, le texte de la constitution d'Innocent IV Quia frequenter a été copié, puis exponctué en marge par un correcteur avec la mention "vacat": "Quia frequenter in electione summorum pontificum colupna Dei... - ...minime computato" avec l'inscription: "Idem" écrite à la fin de la Décrétale précédente qui renvoie à Alexandre III. Sur ce texte qui n’a pas été repris dans le Sexte ; cf. H. Singer, Zeitschrift der Savigny-Stiftung für Rechtesgeschichte, Kan. Abt., VI (1916), 1-140 (éd. Friedberg, 946, Sext. 1, 6, 3, note c). Autres manuscrits recensés : Londres, B.L. ms. Add. 18368, f. 8v ; Paris, BNF ms. latin 14324, f. 234 ; Paris, Bibl. Sainte-Geneviève ms. 339, f. 90 ; Prague, I-B4, f. ? (renseignement aimablement communiqué par Michèle Bégou-Davia).Au f. 133, le titre I, 28 est suivi du texte de Sext. I, 13, 1.Au f.114v, le texte d’Extra 1, 15, 1 §1-6 a été copié une première fois dans le module de la glose à la fin d'un cahier, puis exponctué en marge avec la mention "vacat" et recopié dans le gros module habituel sur un feuillet additionnel (115).Aux ff. 133v-134, les Décrétales 1, 29, 3 et 4, suivies de leurs commentaires, ont été interverties ; de même que les Décrétales 1, 29, 42 et 43, aux ff. 152v-153v. F. 178-360v. "Incipit liber secundus". Extra 2, 1, 1 ; suivi de [HENRICUS DE SEGUSIO, Lectura:] "[D]e Quovultdeo etc. Supple ita statutum est d. n. sed propter hoc plene non subvenitur constronccioni [sic].." - ... Extra 2, 30, 6 "... archid. c. fi. § fi". "Explicit liber secundus. Benedictus sit Deus." (éd.Venise, II, 2-209v). Comme dans le livre I, le libellé inscrit à la fin des titres II, 1 (187), 2 (196v), 5 (202), 13 (240), 14 (247), 15 (249), 18 (252v), 25 (312v), 27 (329v), 28 (357v) correspond à l'inscription des Novelles d'Innocent IV éditées dans le Sexte, livre II, en tête des titres 1-3, 5-7, 9, 12, 14, 15.Au f. 196v, le copiste a copié à la suite les commentaire sur Extra 2, 2, 19 et 20, omettant le texte de Extra 2, 20 qu'il a dû ajouter ensuite dans la marge. Au f. 205, le copiste a mal apprécié l’espace réservé pour Extra 6, 2, le texte commencé normalement en gros module d'écriture, se poursuit en petit module et se termine dans la marge inférieure. De même, au f. 227, les dernières lignes d’ Extra 12, 7 ont dû être écrites dans la marge, avec un signe de renvoi. F. 360v-362. Commentaire anonyme sur Extra 2, 28, 59 De appellationibus: "Ut debitus honor etc. More solito dominus Innocencius premittit causam constitutionis exprimens duas causas motivas: qualiter hec constitutio promulgatur antipophornando... - ... se scit et c. arguta". A noter, f. 1-72v, en marge. PETRUS DE SAMPSONA, Distinctiones super Decretalibus 1, 1, 1-1, 6, 44, excerpta; cf. M. Bertram, "Pierre de Sampson et Bernard de Montmirat...", dans L'Eglise et le droit dans le Midi (XIIIe-XIVe s.) (Cahiers de Fanjeaux, 29), Toulouse, 1994, 37-74 et part. 66, parmi les mss recensés. En marge de l'inscription de l'épitre de Grégoire IX: "Greg. ep. etc. Dominus papa Christi universitatis vicarius set episcopus dicitur singularis quare dominus papa dicatur servus... - ...a papa"; en marge de l'épitre dédicatoire: "Rex pacificus quarum alique propter nimiam similitudinem quedam propter contrarietatem sed numquid in hac compilacione... - ...per totum", incipit A de M. Bertram, art. cit., 64 (1) ; — en marge de la Lectura sur l'épitre dédicatoire: Rex pacificus dicitur esse pacificus et Christus pacem diligit temporalem... - ...approbatur" (1v). — Dernière glose en marge d'Extra 1, 6, 44: "Itaque interim etc. Hii etiam qui pape... - ... et similibus" (72v). A noter, au f. 55v, à la fin de la glose, la signature "P. Sampsone" et au f. 67, "P. Samp.". F. 1-69v, passim et 124v-125. Gloses marginales ajoutées par une main cursive anglaise, contemporaine de la copie. « Doctoribus. Qui faciunt universitatem... - ...dilectus. [signé] Abb(at)is" (Bernardus de Montmirat, Lectura in Decretales, ed. Venise, 1588, I, 2) (1). —En marge de la Lecture sur Extra 1, 6, 42: "B. in apostillis suis dicit quod si aliquis potestatem... - ...commento Hostiensis" (69v).

¿La cultura es un factor que influye en la percepción de las marcas? :Caso: La imagen de marca-país de México entre los turistas españoles

Aquest treball presenta un model comparatiu d’anàlisis de la marca en base a l’inconscient col•lectiu, teoria desenvolupada per C. G. Jung (1991), adequat per Sabrine Dornelles (2010) a l’estudi de les marques comercials i contrastat en aquest treball amb la proposta d’aproximació al Perfil Arquetípic Azteca. Per aquesta raó, s’ha realitzat una revisió bibliográfica en referencia a l’objecte de l’estudi del posicionament de la marca, i en especial, dels atributs vinculats al perfil azteca. Amb l’objectiu de conèixer si la cultura influeix o no, en la percepció d’una marca, s’ha realitzat un pre-test via online amb subjectes de nacionalitat espanyola i de països d’Amèrica llatina (Argentina, Colòmbia, Equador, Perú, República Dominicana i Veneçuela) per al grup de control. 5 Els resultats han sigut tractats tant a nivell d’estadística descriptiva com a mode inferencial. Les dades amb significació p≤ 0,05 mostren els estímuls (atributs) que foren associats o no, amb la marca del país Mèxic. Mentre que l’arquetip occidental (grec) va permetre en major percentatge valorar la marca amb tots els subjectes (espanyols, mexicans i llatins) l’arquetip prehispànic no dóna significació suficient amb els espanyols i llatins, però en canvi aporta matisos en el cas dels mexicans. En referència a l’esmenta’t anteriorment , cal que el proper pas sigui millorar el perfil d’arquetipus azteca.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Transforming growth factor beta 1 production by CD4+ CD25+ regulatory T cells in peripheral blood mononuclear cells from healthy subjects stimulated with Leishmania guyanensis.

Transforming growth factor beta (TGF-beta) has been shown to be a central immunomodulator used by leishmaniae to escape effective mechanisms of protection in human and murine infections with these parasites. However, all the information is derived from studies of established infection, while little is known about TGF-beta production in response to Leishmania stimulation in healthy subjects. In this study, TGF-beta1 production was demonstrated in peripheral blood mononuclear cells from healthy subjects never exposed to leishmaniae in response to live Leishmania guyanensis, and the TGF-beta1-producing cells were described as a distinct subpopulation of CD4(+) CD25(+) regulatory T cells. The suppressive properties of CD4(+) CD25(+) T cells were demonstrated in vitro by their inhibition of production of interleukin 2 (IL-2) and IL-10 by CD4(+) CD25(-) T cells in the presence of either anti-CD3 or L. guyanensis. Although neutralization of TGF-beta1 did not reverse the suppressive activity of CD4(+) CD25(+) T cells activated by anti-CD3, it reversed the suppressive activity of CD4(+) CD25(+) T cells activated by L. guyanensis. Altogether our data demonstrated that TGF-beta1 is involved in the suppressive activity of L. guyanensis-stimulated CD4(+) CD25(+) T cells from healthy controls.

Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development.

Sirt3 is a mitochondrial NAD(+)-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout (LDLR(-/-)) and LDLR/Sirt3 double-knockout (Sirt3(-/-)LDLR(-/-)) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3-deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic core diameter). Likewise, plaque macrophage and T cell infiltration as well as endothelial activation remained unaltered. Electron microscopy of aortic walls revealed no difference in mitochondrial microarchitecture between both groups. Interestingly, loss of Sirt3 was associated with accelerated weight gain and an impaired capacity to cope with rapid changes in nutrient supply as assessed by indirect calorimetry. Serum lipid levels and glucose tolerance were unaffected by Sirt3 deletion in LDLR(-/-) mice. Sirt3 deficiency does not affect atherosclerosis in LDLR(-/-) mice. However, Sirt3 controls systemic levels of oxidative stress, limits expedited weight gain, and allows rapid metabolic adaptation. Thus, Sirt3 may contribute to postponing cardiovascular risk factor development.

A Factor analysis of hidrochemical composition of Llobregat river basin

Hydrogeological research usually includes some statistical studies devised to elucidate mean background state, characterise relationships among different hydrochemical parameters, and show the influence of human activities. These goals are achieved either by means of a statistical approach or by mixing modelsbetween end-members. Compositional data analysis has proved to be effective with the first approach, but there is no commonly accepted solution to the end-member problem in a compositional framework.We present here a possible solution based on factor analysis of compositions illustrated with a case study.We find two factors on the compositional bi-plot fitting two non-centered orthogonal axes to the most representative variables. Each one of these axes defines a subcomposition, grouping those variables thatlay nearest to it. With each subcomposition a log-contrast is computed and rewritten as an equilibrium equation. These two factors can be interpreted as the isometric log-ratio coordinates (ilr) of three hiddencomponents, that can be plotted in a ternary diagram. These hidden components might be interpreted as end-members.We have analysed 14 molarities in 31 sampling stations all along the Llobregat River and its tributaries, with a monthly measure during two years. We have obtained a bi-plot with a 57% of explained totalvariance, from which we have extracted two factors: factor G, reflecting geological background enhanced by potash mining; and factor A, essentially controlled by urban and/or farming wastewater. Graphicalrepresentation of these two factors allows us to identify three extreme samples, corresponding to pristine waters, potash mining influence and urban sewage influence. To confirm this, we have available analysisof diffused and widespread point sources identified in the area: springs, potash mining lixiviates, sewage, and fertilisers. Each one of these sources shows a clear link with one of the extreme samples, exceptfertilisers due to the heterogeneity of their composition.This approach is a useful tool to distinguish end-members, and characterise them, an issue generally difficult to solve. It is worth note that the end-member composition cannot be fully estimated but only characterised through log-ratio relationships among components. Moreover, the influence of each endmember in a given sample must be evaluated in relative terms of the other samples. These limitations areintrinsic to the relative nature of compositional data

APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth.

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family designated APRIL (for a proliferation-inducing ligand). Although transcripts of APRIL are of low abundance in normal tissues, high levels of mRNA are detected in transformed cell lines, and in human cancers of colon, thyroid, and lymphoid tissues in vivo. The addition of recombinant APRIL to various tumor cells stimulates their proliferation. Moreover, APRIL-transfected NIH-3T3 cells show an increased rate of tumor growth in nude mice compared with the parental cell line. These findings suggest that APRIL may be implicated in the regulation of tumor cell growth.

Saeculum IX. Nicolai I,... Epistolae et decreta... Praecedunt B. Servati Lupi,... Flori,... Rodulfi Bituricensis, Walterii Aurelianensis, Rothadi II Suessionensis opera omnia, accurante J.-P. Migne,...

Comprend : Opera omnia

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer.

BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-1 have been associated with increased risk of breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. The current study was conducted to further characterize the association of IGF-1 during pregnancy with maternal breast cancer risk. METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women less than 40 years of age, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred and nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched to each case on age and date at blood donation. Serum IGF-1 concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: No significant associations were observed between serum IGF-1 concentrations and breast cancer risk in both the overall analysis (OR 1.08 (95% CI 0.80-1.47) and in analyses stratified by histological subtype, lag-time to cancer diagnosis, age at pregnancy or age at diagnosis.CONCLUSIONS: There was no association between IGF-1 and maternal breast cancer risk during early pregnancy in this large nested case-control study.Impact:Serum IGF-1 concentrations during early pregnancy may not be related to maternal risk of breast cancer.