G894T and 4a/b Polymorphisms of NOS3 Gene are Not Associated with Cancer Risk: a Meta-analysis


Endothelial nitric oxide synthase (eNOS or NOS3) produces nitric oxide and genetic polymorphisms ofNOS3 gene play significant roles in various processes of carcinogenesis. The results from published studies onthe association between NOS3 G894T and NOS3 intron 4 (4a/b) polymorphisms and cancer risk are conflictingand inconclusive. However, i n order to assess this relationship more precisely, a meta-analysis was performedwith PubMed (Medline), EMBASE and Google web searches until February 2014 to select all published casecontroland cohort studies. Genotype distribution data were collected to calculate the pooled odd ratios (ORs) and95% confidence intervals (CIs) to evaluate the strength of association. A total of 10,546 cancer cases and 10,550controls were included from twenty four case-control studies for the NOS3 G894T polymorphism. The resultsindicated no significant association with cancer risk as observed in allelic (T vs G: OR=1.024, 95%CI=0.954to 1.099, p=0.508), homozygous (TT vs GG: OR=1.137, 95%CI=0.944 to 1.370, p=0.176), heterozygous (GT vsGG: OR=0.993, 95%CI=0.932 to 1.059, p=0.835), recessive (TT vs GG+GT: OR=1.100, 95%CI=0.936 to 1.293,p=0.249) and dominant (TT+GT vs GG: OR=1.012, 95%CI=0.927 to 1.105, p=0.789) genetic models. Similarly,a total of 3,449 cancer cases and 3,691 controls were recruited from fourteen case-control studies for NOS3 4a/bpolymorphism. Pooled results indicated no significant association under allelic (A vs B: OR=0.981, 95%CI=0.725to 1.329, p=0.902), homozygous (AA vs BB: OR=1.166, 95%CI=0.524 to 2.593, p=0.707), heterozygous (BA vsBB: OR=1.129, 95%CI=0.896 to 1.422, p=0.305), dominant (AA+BA vs BB: OR=1.046, 95%CI=0.779 to 1.405,p=0.763) and recessive (AA vs BB+BA: OR=1.196, 95%CI=0.587 to 2.439, p=0.622) genetic contrast models. Thismeta-analysis suggests that G894T and 4a/b polymorphisms of NOS3 gene are not associated with increased ordecreased risk of overall cancer.