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Research: LEE and COLLEAGUES,
Listed in Issue 173
Abstract
LEE and COLLEAGUES, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. leekyou@mail.nih.gov evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular nitric oxide (NO).
Background
Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in prostate carcinogenesis, potentially modulated by environmental exposures.
Methodology
We evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular NO: NOS2A [inducible nitric oxide synthase (NOS); -2892T>C, Ex16 + 14C>T (S608L), IVS16 + 88T>G and IVS20 + 524G>A] and NOS3 [endothelial NOS; IVS1-762C>T, Ex7-43C>T (D258D), IVS7-26A>G, Ex8-63G>T (E298D) and IVS15-62G>T]. Prostate cancer cases (n = 1320) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were frequency matched to controls (n = 1842), by age, race, time since initial screening and year of blood draw. An antioxidant score [range 3-12; low (3-7) versus high (8-12)] was created by summing the quartile levels of vitamin E, beta-carotene and lycopene, which were coded from 1 to 4, respectively.
Results
The global tests for all eight single-nucleotide polymorphisms (SNPs) (excluding NOS2A-2892T>C, with low minor allele frequency) were statistically significant for prostate cancer (P = 0.005), especially for aggressive cancer (stage III-IV or Gleason score > or = 7) (P = 0.01). The NOS2A IVS16 + 88 GT/TT was associated with increased prostate cancer risk (odds ratio = 1.24, 95% confidence interval = 1.00-1.54), whereas the IVS20 + 524 AG/GG was associated with decreased risk (0.77, 0.66-0.90). The NOS3 IVS7-26GG was associated with increased prostate cancer risk (1.33, 1.07-1.64). All these SNPs showed significant associations with aggressive cancer and not for non-aggressive cancer. In the evaluation of effect modification, the effect of the NOS2A IVS16 + 88 GT/TT on aggressive cancer was stronger among subjects with higher antioxidant intake (1.61, 1.18-2.19; P(interaction) = 0.01).
Conclusion
Our results suggest that NOS gene polymorphisms are genetic susceptibility factors for aggressive prostate cancer.
References
Lee KM, Kang D, Park SK, Berndt SI, Reding D, Chatterjee N, Chanock S, Huang WY and Hayes RB. Nitric oxide synthase gene polymorphisms and prostate cancer risk. Carcinogenesis. 30(4):621-5. Apr 2009. Source: NLM. PMC2664454 [Available on 04/01/10].
Comment
In view of the currently limited reliable options available for prostate cancer screening, apart from PSA measures, the above research, which, if replicated and verified by further research, could provide a genetic test for aggressive prostate cancer.
