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NAD(P)H:quinone oxi...
NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer
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Fagerholm, Rainer (author)
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Hofstetter, Barbara (author)
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Tommiska, Johanna (author)
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Aaltonen, Kirsimari (author)
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Vrtel, Radek (author)
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Syrjäkoski, Kirsi (author)
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Kallioniemi, Anne (author)
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Kilpivaara, Outi (author)
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Mannermaa, Arto (author)
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Kosma, Veli-Matti (author)
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Uusitupa, Matti (author)
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Eskelinen, Matti (author)
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Kataja, Vesa (author)
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Aittomäki, Kristiina (author)
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von Smitten, Karl (author)
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Heikkilä, Päivi (author)
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Lukas, Jiri (author)
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Holli, Kaija (author)
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Bartkova, Jirina (author)
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- Blomqvist, Carl (author)
- Uppsala universitet,Enheten för onkologi
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Bartek, Jiri (author)
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Nevanlinna, Heli (author)
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(creator_code:org_t)
- 2008-05-30
- 2008
- English.
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:7, s. 844-53
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.558C>T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P = 0.002, N = 1,005; P = 0.005, N = 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P = 7.52 x 10(-6)) and in p53-aberrant tumors (P = 6.15 x 10(-5)). 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 that the NQO1 genotype is a prognostic and predictive marker for breast cancer.
Keyword
- MEDICINE
- MEDICIN
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- ref (subject category)
- art (subject category)
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Fagerholm, Raine ...
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Hofstetter, Barb ...
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Tommiska, Johann ...
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Aaltonen, Kirsim ...
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Vrtel, Radek
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Syrjäkoski, Kirs ...
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show more...
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Kallioniemi, Ann ...
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Kilpivaara, Outi
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Mannermaa, Arto
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Kosma, Veli-Matt ...
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Uusitupa, Matti
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Eskelinen, Matti
-
Kataja, Vesa
-
Aittomäki, Krist ...
-
von Smitten, Kar ...
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Heikkilä, Päivi
-
Lukas, Jiri
-
Holli, Kaija
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Bartkova, Jirina
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Blomqvist, Carl
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Bartek, Jiri
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Nevanlinna, Heli
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show less...
- Articles in the publication
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Nature Genetics
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Uppsala University