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.
- MeSH
- chinonreduktasy biosyntéza genetika MeSH
- DNA nádorová krev genetika MeSH
- genetická transkripce MeSH
- jednonukleotidový polymorfismus MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- NAD(P)H dehydrogenasa (chinon) biosyntéza genetika MeSH
- nádorové biomarkery biosyntéza genetika MeSH
- nádory prsu krev enzymologie genetika patologie MeSH
- přežití bez známek nemoci MeSH
- superoxiddismutasa biosyntéza genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The aim of this study was to further clarify the recently reported role of NAD(P)H:quinone oxidoreductase 1 (NQO1) as a strong prognostic and predictive factor in breast cancer. METHODS: NQO1 transcript levels were monitored in mammary tumors by real-time polymerase chain reaction. NQO1 protein levels were immunohistochemically determined in formalin-fixed paraffin-embedded tissues. NQO1 polymorphism (Pro187Ser, rs1800566) was also assessed. Evaluation (N=52) and validation (N=53) sets were analyzed subsequently. RESULTS: Carriers of variant NQO1-Ser allele had significantly more frequently NQO1-negative protein expression (P=0.001) in both sets. NQO1 transcript levels in samples with negative protein expression were significantly lower than in those with positive NQO1 protein expression (P=0.007) in both sets. Patients with stages 0/I/II had more often positive NQO1 protein expression than patients with stages III/IV (P=0.022) in the evaluation set. Significant association between NQO1 protein expression and TP53 protein status was also found (P=0.037). However, both associations were not replicated by analysis of the validation set. Analysis of both sets combined did not show significant association of NQO1 protein expression either with stage (P=0.231) or with TP53 protein status (P>0.999). Thus, the results observed in the evaluation set were effects of small sample size. CONCLUSION: The role of NQO1 in human mammary gland carcinogenesis does not seem to be directly associated with classical clinico-pathological factors.
- MeSH
- genetická predispozice k nemoci MeSH
- imunohistochemie MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- NAD(P)H dehydrogenasa (chinon) genetika MeSH
- nádory prsu enzymologie genetika patologie MeSH
- prolin genetika MeSH
- regulace genové exprese u nádorů MeSH
- serin genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
