. . "Kosma, Veli-Matti" . "RIV/61989592:15110/08:00009724" . "NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer"@en . "Bartkova, Ji\u0159ina" . "S, Z(MSM6198959216)" . "von Smitten, Karl" . "Fagerholm1, Rainer" . "Kilpivaara, Outi" . "22"^^ . . . "15110" . "Kataja, Vesa" . "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" . . "10"^^ . "7" . "Vrt\u011Bl, Radek" . "RIV/61989592:15110/08:00009724!RIV10-MSM-15110___" . . . "NQO1; oxidative stress; carcinogenesis; p53; breast cancer; treatment resistance"@en . . "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"@en . . . . "NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer" . . "Nevanlinna, Heli" . "381478" . "Holli, Kaija" . "40" . "1061-4036" . "NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer"@en . "2"^^ . "B\u00E1rtek, Ji\u0159\u00ED" . "Heikkil\u00E4, P\u00E4ivi" . . "[F44C377F6C1B]" . "NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer" . . . . . "Lukas, Ji\u0159\u00ED" . "Kallioniemi, Anne" . "Nature genetics" . "Syrj\u00E4koski, Kirsi" . "Blomqvist, Carl" . "Eskelinen, Matti" . "Mannermaa, Arto" . . "Hofstetter, Barbara" . "Aittom\u00E4ki, Kristiina" . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . . "Uusitupa, Matti" . . "Tommiska, Johanna" . "Aaltonen, Kirsimari" .