Lack of association between NOS3 Glu298Asp and breast cancer risk: a case-control study.
ABSTRACT Nitric oxide (NO) plays a central role in the physiololgy and pathology of diverse tissues. Different studies provide data suggesting that the endothelial cell nitric oxide synthase (NOS3) expression in peritumoral microvessels might be a prognostic indicator in breast cancer patients. However, the putative contribution of common NOS3 germline variants to breast cancer risk remained unknown. A recent work comprising 269 breast cancer patients and 244 controls suggested that NOS3 Glu298Asp polymorphism is associated to breast cancer risk (OR=1.9). We performed an independent analysis of these results in 440 unrelated patients and 321 controls from Spanish population. Although our study was 90% powered to detect ORs >/=1.55, did not find any significant difference in the Glu298Asp allele distribution between cases and controls (P > 0.42). These putative reasons for this result are discussed.
- Value in Health 01/2010; 13(7). · 2.19 Impact Factor
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ABSTRACT: Genetic polymorphism of endothelial nitric oxide synthase (NOS3) rs1799983 (Glu298Asp) has been implicated to alter the risk of prostate cancer, but the results are controversial. Two investigators independently searched the PubMed, Cochrane Library, and Embase electronic databases up to September 30, 2013. Summary odds ratios (OR) and 95 % confidence interval (CI) for rs1799983 polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 11.0. A total of 7 independent studies, including 1,792 cases and 2,411 controls, were identified. Our analysis suggested that rs1799983 was associated with prostate cancer risk in overall population under dominant model (OR = 1.15, 95%CI = 1.01-1.30, P = 0.03) and allelic model (OR = 1.11, 95%CI = 1.00-1.22, P = 0.04). In the subgroup analysis, we detected no association between rs1799983 polymorphism and prostate risk in Caucasian population under all the genetic models. This meta-analysis showed the evidence that NOS3 rs1799983 polymorphism was associated with a risk of prostate cancer development in overall populations.Tumor Biology 04/2014; · 2.52 Impact Factor
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ABSTRACT: Breast cancer is the most frequent cancer type among women in western countries. In addition to established risk factors like hormone replacement therapy, oxidative stress may play a role in carcinogenesis through an unbalanced generation of reactive oxygen species that leads to genetic instability. The aim of this study is to assess the influence of common single nucleotide polymorphisms (SNPs) in candidate genes related to oxidative stress on postmenopausal breast cancer risk. We genotyped 109 polymorphisms (mainly tagging SNPs) in 22 candidate genes in 1,639 postmenopausal breast cancer cases and 1,967 controls (set 1) from the German population-based case-control study "MARIE". SNPs showing association in set 1 were tested in further 863 cases and 2,863 controls from MARIE (set 2) using a joint analysis strategy. Six polymorphisms evaluated in the combined set showed significantly modified breast cancer risk per allele in the joint analysis, including SNPs in CYBA (encoding a subunit of the NADPH oxidase: rs3794624), MT2A (metallothionein 2A: rs1580833), TXN (thioredoxin: rs2301241), and in TXN2 (thioredoxin 2: rs2267337, rs2281082, rs4821494). Associations with the CYBA rs3794624 (OR per allele: 0.93, 95% CI 0.87-0.99) and TXN rs2301241 variants (OR per allele: 1.05, 95% CI 1.00-1.10) were confirmed in the summary risk estimate analysis using up to three additional studies. We found some evidence for association of polymorphisms in genes of the thioredoxin system, CYBA, and MT2A with postmenopausal breast cancer risk. Summary evidence including independent datasets indicated moderate effects in CYBA and TXN that warrant confirmation in large independent studies.International Journal of Cancer 09/2011; 129(6):1467-76. · 6.20 Impact Factor