Polymorphisms In The Nitric-Oxide Synthase 2 Gene And Prostate Cancer Pathogenesis
Charlotta Ryk1, Petra de Verdier1, Emmie Montgomery1
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Redox Biology
|February 7, 2017
Summary
Polymorphisms in the nitric oxide synthase 2 (NOS2) gene are linked to prostate cancer risk and progression. Specific genetic variations may influence aggressive tumor development and patient outcomes.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Nitric oxide synthase (NOS) polymorphisms affect nitric oxide (NO) levels and are associated with various disease risks.
- The study focuses on single nucleotide polymorphisms (SNPs) and a (CCTTT)n microsatellite within the NOS2 gene.
Purpose of the Study:
- To investigate associations between NOS2 gene polymorphisms and prostate cancer.
- To explore the impact of these polymorphisms on prostate cancer pathogenesis, including tumor aggressiveness and patient survival.
Main Methods:
- Genotyping of 145 SNPs and a (CCTTT)n microsatellite in the NOS2 gene using Affymetrix 5.0 chip, DNA fragment analysis, and sequencing.
- Analysis of 3161 prostate cancer patients and 2149 controls from a Swedish population-based GWAS study.
- Correlation of genotypes with clinical data including tumor stage, Gleason score, PSA levels, metastasis, and cancer-specific death.
Main Results:
- Patients with longer (CCTTT)n repeats (LL) showed a decreased risk of highly aggressive tumors but a threefold increased risk of dying from prostate cancer compared to SS homozygotes.
- SNP alleles co-varying with the long (CCTTT)n allele were associated with lower risk of aggressive tumors and higher mortality risk.
- An increasing proportion of lymph node metastases was observed with longer (CCTTT)n allele lengths (p=0.033).
Conclusions:
- NOS2 polymorphisms may influence the risk of developing aggressive prostate cancer.
- These genetic variations could impact prostate cancer pathogenesis, potentially by altering intracellular nitric oxide levels.
- Further research is warranted to elucidate the precise mechanisms by which NOS2 polymorphisms affect prostate cancer outcomes.
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