Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community’s Seventh Framework Programme under grant agreement n8 223175 (HEALTH-F2–2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program and the Ministry of Economic Development, Innovation and Export Trade of Quebec (PSR-SIIRI-701). Additional support for the iCOGS infrastructure was provided by the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112—the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The ABCFS and OFBCR work was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement t by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and M.C.S. is a NHMRC Senior Research Fellow. The OFBCR work was also supported by the Canadian Institutes of Health Research ‘CIHR Team in Familial Risks of Breast Cancer’ program. The ABCS was funded by the Dutch Cancer Society Grant no. NKI2007-3839 and NKI2009-4363. The ACP study is funded by the Breast Cancer Research Trust, UK. The work of the BBCC was partly funded by ELAN-Programme of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). E.S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy’s & St. Thomas’ NHS Foundation Trust in partnership with King’s College London, UK. Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z). I.T. is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by the Fondation de France, the French National Institute of Cancer (INCa), The National League against Cancer, the National Agency for Environmental l and Occupational Health and Food Safety (ANSES), the National Agency for Research (ANR), and the Association for Research against Cancer (ARC). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.The CNIO-BCS was supported by the Genome Spain Foundation the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario PI11/00923 and PI081120). The Human Genotyping-CEGEN Unit, CNIO is supported by the Instituto de Salud Carlos III. D.A. was supported by a Fellowship from the Michael Manzella Foundation (MMF) and was a participant in the CNIO Summer Training Program. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence e data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), as well as the Department of Internal Medicine , Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus Bonn, Germany. The HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HERPACC was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by a research grant from Takeda Science Foundation , by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by National Cancer Center Research and Development Fund. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to N.B), and the Friends of Hannover Medical School (to N.B.). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Stockholm Cancer Foundation and the Swedish Cancer Society. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation , the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704, 454508). Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). G.C.T. and P.W. are supported by the NHMRC. LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018 and 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute’s Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the ‘Stichting tegen Kanker’ (232-2008 and 196-2010). The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I), the Federal Ministry of Education Research (BMBF) Germany (01KH0402), the Hamburg Cancer Society and the German Cancer Research Center (DKFZ). MBCSG is supported by grants from the Italian Association ciation for Cancer Research (AIRC) and by funds from the Italian citizens who allocated a 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’). The MCBCS was supported by the NIH grants (CA122340, CA128978) and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The MEC was supported by NIH grants CA63464, CA54281, CA098758 and CA132839. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research (grant CRN-87521) and the Ministry of Economic Development, Innovation and Export Trade (grant PSR-SIIRI-701). MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19,tel:08/1/35/19./550), Singapore and the National medical Research Council, Singapore (NMRC/CG/SERI/2010). The NBCS was supported by grants from the Norwegian Research council (155218/V40, 175240/S10 to A.L.B.D., FUGE-NFR 181600/ V11 to V.N.K. and a Swizz Bridge Award to A.L.B.D.). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NLCP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. pKARMA is a combination of the KARMA and LIBRO-1 studies. KARMA was supported by Ma¨rit and Hans Rausings Initiative Against Breast Cancer. KARMA and LIBRO-1 were supported the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linnaeus Centre (Contract ID 70867902) financed by the Swedish Research Council. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (A∗STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation KC was financed by the Swedish Cancer Society (5128-B07-01PAF). The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The SBCS was supported by Yorkshire Cancer Research S305PA, S299 and S295. Funding for the SCCS was provided by NIH grant R01 CA092447. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by a programme grant from Cancer Research UK (C490/A10124) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the National Medical Research Council Start-up Grant and Centre Grant (NMRC/CG/NCIS /2010). The recruitment of controls by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC) was funded by the Biomedical Research Council (grant number: 05/1/21/19/425). SKKDKFZS is supported by the DKFZ. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. K. J. is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The TNBCC was supported by the NIH grant (CA128978), the Breast Cancer Research Foundation , Komen Foundation for the Cure, the Ohio State University Comprehensive Cancer Center, the Stefanie Spielman Fund for Breast Cancer Research and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. Part of the TNBCC (DEMOKRITOS) has been co-financed by the European Union (European Social Fund – ESF) and Greek National Funds through the Operational Program ‘Education and Life-long Learning’ of the National Strategic Reference Framework (NSRF)—Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. The TWBCS is supported by the Institute of Biomedical Sciences, Academia Sinica and the National Science Council, Taiwan. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.This is the advanced access published version distributed under a Creative Commons Attribution License 2.0, which can also be viewed on the publisher's webstie at: http://hmg.oxfordjournals.org/content/early/2014/07/04/hmg.ddu311.full.pdf+htm

Influência de variáveis limnológicas sobre a comunidade das macrófitas aquáticas em rios e lagoas da Cadeia do Espinhaço, Minas Gerais, Brasil

Resumo Plantas aquáticas e amostras de água foram coletadas em cinco lagoas e três rios na região da Cadeia do Espinhaço, entre dezembro de 2001 e agosto de 2003. Lagoas: Tanque da Fazenda, Comprida, Arame, Americana e Estivinha. Rios: Corrento, Taquaral e Preto. Foram medidas as seguintes variáveis: temperatura da água, transparência da coluna de água, pH, condutividade elétrica, oxigênio dissolvido, demanda bioquímica de oxigênio, demanda química de oxigênio, nitrogênio amoniacal, nitrogênio total, fósforo reativo solúvel e fosfato total. Nos ambientes lóticos os maiores valores de condutividade foram registrados para os rios Preto e Corrento e foram correlacionados ao aporte de nutrientes naturais. Considerando os ambientes lênticos, nas lagoas Americana e Estivinha foram verificados os maiores valores de condutividade elétrica e DQO. O maior valor de transparência foi observado na lagoa Tanque da Fazenda. Na ordenação das espécies, foi observada maior riqueza de macrófitas junto às lagoas Americana, Estivinha e Comprida, cujas correlações mais fortes foram com os valores de temperatura, pH e concentração de nitrogênio. A ordenação das formas biológicas sugeriu a presença de espécies flutuantes fixas nos ambientes mais ricos em nitrogênio e com temperaturas da água mais elevadas. Provavelmente, a diversidade de ambientes identificada neste estudo e as diferentes características físicas e químicas estão refletidas na composição florística e nas interações com o ecossistema

Avaliação da concentração de efeito do glifosato para controle de Eichhornia crassipes e Salvinia sp.

RESUMO A possibilidade do uso de herbicidas em ecossistema aquático para controle de macrófitas quando em condições de desequilíbrio levou à necessidade de estudos que avaliam a concentração de efeito que seja eficiente e ecologicamente equilibrada, sem causar maiores impactos aos organismos não alvo e ao ecossistema aquático. O glifosato é o princípio ativo de alguns herbicidas e é conhecido pela sua eficácia, amplo espectro de ação e baixa toxicidade. Neste trabalho foi investigada a menor concentração de efeito para controle da Eichhornia crassipes e da Salvinia sp em experimentos realizados em triplicata e observados pelo período de 20 dias após aplicações de glifosato nas concentrações de 6,25; 12,5; 25,0; 50,0 e 100 L.ha-1. Como resultado, verificou-se que apenas a concentração de 100 L.ha-1 apresentou diferença significativa de efeito comparada ao controle. O efeito ao final do vigésimo dia foi superior a 90%, tornando-se aparente a partir do décimo dia. Existiu uma pequena diferença na sensibilidade entre as espécies, no entanto, a concentração de efeito foi semelhante. A dose de 100 L.ha-1 impediu a ocorrência de rebrota, no prazo de 30 dias, e causou efeito residual pobre em espécies vegetais inseridas no ambiente após a aplicação do herbicida

Composição florística da vegetação arbórea de um trecho de floresta de galeria do Parque Estadual do Rola-Moça na Região Metropolitana de Belo Horizonte, MG, Brasil

O estudo foi desenvolvido em um trecho de floresta de galeria na Área de Proteção Especial do Barreiro integrante do Parque Estadual do Rola-Moça, Região Metropolitana de Belo Horizonte (MG). O objetivo foi determinar a composição desse trecho de floresta, importante como subsídio à projetos de recuperação e enriquecimento dessa tipologia. A composição florística foi determinada a partir de uma amostragem fitossociológica na qual foi utilizado o método de parcelas sendo demarcadas 36 parcelas de 10×10m, além de coletas complementares realizadas fora da amostragem. Foram relacionados todos os indivíduos arbóreos com circunferência de tronco a 1,30m do solo igual ou superior a 15cm. Encontrou-se 97 espécies, distribuídas por 79 gêneros de 43 famílias. A composição florística quando comparada com outras florestas de galeria no Sudeste e Centro-Oeste apresentou baixa similaridade, sendo a maior semelhança verificada com as florestas do sul de Minas. A riqueza florística apresentou diferenças significativas quando relacionada à distância do córrego, sendo as parcelas situadas aos 28, 64 e 82m as responsáveis pelos maiores valores de riqueza

Levantamento florísitico na Estação Ecológica do Tripuí, Ouro Preto, MG

Realizou-se o levantamento florístico na Estação Ecológica do Tripuí, Ouro Preto, MG (43º34'33" W e 20º23'45"S). O clima da região é do tipo mesotérmico, com inverno seco (Cwb sg. Köppen) e com temperaturas médias oscilando entre 14º e 19ºC. A Estação apresenta como principais tipos vegetacionais as florestas mesófilas estacionais, o cerrado, a vegetação aquática (brejos, lagoa artificial e córregos) e as formações sucessionais ('candeial'). Para o levantamento florístico utilizou-se o método de parcelas e coletas por trilhas e caminhos, sendo identificadas 101 famílias, 242 gêneros e 462 espécies. As famílias que apresentaram maior riqueza específica foram Asteraceae (10,82%), Melastomataceae (8,22%), Myrtaceae (7,14%) e Rubiaceae (4,76%)

MORPHOLOGIC ALTERATIONS IN Eichhornia crassipes (water hyacinth) (Mart.) Solms-Laubach, DISPLAYED to RAISED MERCURY CONCENTRATIONS

Este trabalho teve como objetivo verificar as possíveis alterações morfológicas causadas em Eichhornia crassipes (aguapé) por mercúrio, avaliando-se os efeitos tóxicos desse metal sobre o crescimento dessa espécie. Os experimentos tiveram duração de cinco dias, em frascos escuros contendo 0,5 L de solução de Hoagland e Arnon (1950), com ¼ da força iônica original e pH 6,5, acrescida de diferentes concentrações de nitrato de mercúrio dihidratado [Hg (NO3)2. 2 H2O]: 0,5; 2,5; 5,0 e 10,0 mg L-1, sendo cada tratamento realizado em triplicata. Os indivíduos de todos os tratamentos, exceto o tratamento controle, apresentaram sintomas visuais de toxidez, observando-se, cloroses, enrugamento e enrolamento da lâmina foliar e necroses. Os resultados mostraram que a proporção de injúrias aumentou com a elevação da concentração do metal em solução. A produção da biomassa possivelmente foi afetada pelas dosagens de mercúrio, causando redução na ordem de 5,4%, 9,2%, 9,0% e 14,2% para as doses de 0,5; 2,5; 5,0 e 10,0 mg L-1 de mercúrio, respectivamente. Já os indivíduos controle aumentaram a massa fresca em 9,0%, aproximadamente. As lesões foliares observadas até o término do ensaio não ocasionaram a morte de nenhum dos indivíduos. Sugere-se que sejam desenvolvidos estudos anatômicos, fisiológicos e químicos para a obtenção de dados que poderão evidenciar o potencial fitorremediador dessa espécie a fim de ser futuramente utilizada e recomendada para a remoção de mercúrio em ambientes aquáticos.The objective of this work is to verify the possible morphologic changes observed in Eichhornia crassipes (water hyacinths) due to mercury, evaluating the toxic effects of this metal on the development of this species. The experiments were carried out during five days in dark bottles with 0,5 L of Hoagland and Arnon (1950) solution, with ¼ of the original ionic force and pH 6.5, added of different levels of concentration of dihydrated mercury nitrate [Hg (NO3)2. 2 H2O]: 0.5; 2.5; 5.0 e 10.0 mg L-1, being each treatment carried out in triplicates. All treated individuals, except those of the control treatment, presented visual symptoms of toxicity and chlorosis, wrinkling and rolling up of the foliar blade and necrosis. The results showed that the higher the concentration of the metal in the solution the higher the proportion of injuries. The production of biomass was possibly affected by dosages of mercury, decreasing 5.4%, 9.2%, 9.0% and 14.2% when the doses of mercury were 0.5; 2.5; 5.0 and 10.0 mg L-1 respectively. Whereas the new mass of treatment control individuals increased 9.0%, approximately. The foliar injuries were not mortal until the ending of this experiment. It is suggested the development of anatomical physiological and chemical studies for the obtention of data that could make evident the phytoremediator potential of this species in order to be used and recommended for the removal of the mercury in aquatic environments