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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F08%3A00009724%21RIV10-MSM-15110___
rdf:type
skos:Concept n13:Vysledek
dcterms:description
NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53. We find that a homozygous common missense variant (NQO1*2, rs1800566(T), NM_000903.2:c.558C4T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P 1/4 0.002, N 1/4 1,005; P 1/4 0.005, N 1/4 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P 1/4 7.52 106) and in p53-aberrant tumors (P 1/4 6.15 105). Survival after metastasis was reduced among NQO1*2 homozygotes, further implicating NQO1 deficiency in cancer progression and treatment resistance. Consistently, response to epirubicin was impaired in NQO1*2-homozygous breast carcinoma cells in vitro, reflecting both p53-linked and p53 independent roles of NQO1. We propose a model of defective anthracycline response in NQO1-deficient breast tumors, along with increased genomic instability promoted by elevated reactive oxygen species (ROS), and suggest NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53. We find that a homozygous common missense variant (NQO1*2, rs1800566(T), NM_000903.2:c.558C4T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P 1/4 0.002, N 1/4 1,005; P 1/4 0.005, N 1/4 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P 1/4 7.52 106) and in p53-aberrant tumors (P 1/4 6.15 105). Survival after metastasis was reduced among NQO1*2 homozygotes, further implicating NQO1 deficiency in cancer progression and treatment resistance. Consistently, response to epirubicin was impaired in NQO1*2-homozygous breast carcinoma cells in vitro, reflecting both p53-linked and p53 independent roles of NQO1. We propose a model of defective anthracycline response in NQO1-deficient breast tumors, along with increased genomic instability promoted by elevated reactive oxygen species (ROS), and suggest
dcterms:title
NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer
skos:prefLabel
NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer
skos:notation
RIV/61989592:15110/08:00009724!RIV10-MSM-15110___
n3:aktivita
n8:S n8:Z
n3:aktivity
S, Z(MSM6198959216)
n3:cisloPeriodika
7
n3:dodaniDat
n16:2010
n3:domaciTvurceVysledku
n15:9127917 n15:6201822
n3:druhVysledku
n5:J
n3:duvernostUdaju
n14:S
n3:entitaPredkladatele
n18:predkladatel
n3:idSjednocenehoVysledku
381478
n3:idVysledku
RIV/61989592:15110/08:00009724
n3:jazykVysledku
n17:eng
n3:klicovaSlova
NQO1; oxidative stress; carcinogenesis; p53; breast cancer; treatment resistance
n3:klicoveSlovo
n4:p53 n4:breast%20cancer n4:NQO1 n4:oxidative%20stress n4:carcinogenesis n4:treatment%20resistance
n3:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n3:kontrolniKodProRIV
[F44C377F6C1B]
n3:nazevZdroje
Nature genetics
n3:obor
n7:EB
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
22
n3:rokUplatneniVysledku
n16:2008
n3:svazekPeriodika
40
n3:tvurceVysledku
Kosma, Veli-Matti Bartkova, Jiřina von Smitten, Karl Fagerholm1, Rainer Kilpivaara, Outi Kataja, Vesa Vrtěl, Radek Nevanlinna, Heli Holli, Kaija Bártek, Jiří Heikkilä, Päivi Lukas, Jiří Kallioniemi, Anne Syrjäkoski, Kirsi Blomqvist, Carl Eskelinen, Matti Mannermaa, Arto Hofstetter, Barbara Aittomäki, Kristiina Uusitupa, Matti Tommiska, Johanna Aaltonen, Kirsimari
n3:zamer
n12:MSM6198959216
s:issn
1061-4036
s:numberOfPages
10
n9:organizacniJednotka
15110