title: Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas.
abstract: Associations of transcript levels of oxidative stress-modifying genes SOD2, SOD3, NQO1 and NQO2 and their functional single nucleotide polymorphisms (SNPs) rs4880, rs1799895, rs2536512, rs699473, rs1800566 and rs1143684 with prognosis of breast cancer patients were studied. SNPs were assessed by allelic discrimination in a cohort of 321 breast cancer patients from the Czech Republic. Transcript levels were determined by real-time polymerase chain reaction (PCR) with absolute quantification in tumor and adjacent non-neoplastic control tissues. Both genotypes and transcript levels were then compared with available clinical data on patients. Patients carrying low activity allele Leu in NQO2 rs1143684 had a greater incidence of stage 0 or I disease (i.e., better prognosis) than patients with the Phe/Phe genotype. This association was more evident in patients without expression of progesterone receptors (p = 0.031). Patients carrying the Thr allele in SOD3 rs2536512 SNP had a significantly greater incidence of tumors expressing estrogen receptors than patients carrying the Ala/Ala genotype (p = 0.007). SOD3 transcript level was significantly higher in grade 1 or 2 tumors than in grade 3 tumors (p = 0.006). Patients carrying T allele in SOD3 rs699473 SNP had significantly poorer progression-free survival (PFS) than patients carrying the CC genotype (p = 0.038). The same applied to the subgroup of patients treated by hormonal regimens (p = 0.021). Patients carrying the high activity Ala/Ala genotype in SOD2 (rs4880) had significantly poorer PFS than Val allele carriers in the group treated by cyclophosphamide but not hormonal regimens (p = 0.004). Our results suggest that NQO2, SOD2 and SOD3 may significantly modify prognosis of breast cancer patients and that their significance should be further characterized.
authors.affiliation: Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
authors.forename: Miluse
authors.initials: M
authors.lastname: Hubackova
authors.forename: Radka
authors.initials: R
authors.lastname: Vaclavikova
authors.forename: Marie
authors.initials: M
authors.lastname: Ehrlichova
authors.forename: Marcela
authors.initials: M
authors.lastname: Mrhalova
authors.forename: Roman
authors.initials: R
authors.lastname: Kodet
authors.forename: Katerina
authors.initials: K
authors.lastname: Kubackova
authors.forename: David
authors.initials: D
authors.lastname: Vrána
authors.forename: Ivan
authors.initials: I
authors.lastname: Gut
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011808:Quinone Reductases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D000099156:Superoxide Dismutase 2
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C441642:SOD3 protein, human; C447479:NQO1 protein, human; C419642:NRH - quinone oxidoreductase2