One of the most significant SNPs associated with recurrence, rs4639, is located in 39-UTR of NEIL2. Luciferase reporter assay results showed that hsa-mir-421 and hsa-mir-1200 miRNAs had similar inhibitory effects on both wildtype and variant rs4639 expression. Since either miRNAs showed similar inhibitory effects on both wildtype and variant genotypes, it is possible that rs4639 may not be the causative variant but functions as a tagging SNP for other polymorphisms that may contribute to bladder cancer recurrence by altering NEIL2 expression or function. Alternatively, the variant allele of this SNP may affect targeting by other miRNAs. Future fine mapping of the regions surrounding the most significant tagSNPs are needed to identify the causal genetic variations and their molecular mechanisms. We also identified a significant gene-dosage effect for the six tagging SNPs that showed significant main effects. Patients with the largest number of unfavorable genotypes had the highest risk of NMIBC recurrence, suggesting that additional risk genotypes within this key pathway were detrimental. This highlights the importance of assessing multiple SNPs within a shared pathway for clinical outcome assessment. In Doxorubicin summary, we showed that genetic polymorphisms of the oxidative stress pathway genes may modulate the risk of NMIBC recurrence and progression in BCG treated patients. Further, we have conducted a relatively comprehensive query of the oxidative stress pathway polymorphisms with detailed clinical information and analyses, which provided substantial evidence for the involvement of this pathway in the clinical outcomes of bladder cancer patients, particularly with BCG treatment. There are some limitations in this study. For example, only Caucasians were included. It would be interesting to exam these SNPs in minority populations. Additionally, sample size is not particularly large, although power calculation showed that our analysis had sufficient power to detect the main effects analyzed. Although our data are largely internally validated, future replication studies in independent populations are needed to validate some of the results and to translate the findings to clinical trials. A metagenome sequence sample is obtained by sequencing the DNA of a mixture of microorganisms from an environment of interest. Identification of the taxonomic affiliation of DNA sequences, either for individual reads or assembled contigs, is an essential step prior to further analysis, such as characterization of the functional and metabolic capabilities of the sequenced microbial community. Various taxonomic assignment methods exist, which can be divided into three categories: sequence composition-based, sequence alignment-based and hybrids; see, and respectively for examples. Sequence composition based methods use short substrings to represent a sequence as a vector of fixed length, which is used to assess similarity among sequences. Such a representation is known as a “genomic signature” and is more conserved between evolutionarily close species than distant species.