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

  • Haque, Shafiul (Department of Biosciences, Jamia Millia Islamia (A Central University)) ;
  • Mandal, Raju K (Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University) ;
  • Akhter, Naseem (Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University) ;
  • Panda, Aditya K (Centre for Life Science, School of Natural Sciences, Central University of Jharkhand) ;
  • Hussain, Arif (School of Life Sciences, Manipal University) ;
  • Khan, Saif (Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il) ;
  • Lohani, Mohtashim (Department of Biosciences, Integral University)
  • Published : 2015.04.14


Endothelial nitric oxide synthase (eNOS or NOS3) produces nitric oxide and genetic polymorphisms of NOS3 gene play significant roles in various processes of carcinogenesis. The results from published studies on the association between NOS3 G894T and NOS3 intron 4 (4a/b) polymorphisms and cancer risk are conflicting and inconclusive. However, i n order to assess this relationship more precisely, a meta-analysis was performed with PubMed (Medline), EMBASE and Google web searches until February 2014 to select all published case-control and cohort studies. Genotype distribution data were collected to calculate the pooled odd ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of association. A total of 10,546 cancer cases and 10,550 controls were included from twenty four case-control studies for the NOS3 G894T polymorphism. The results indicated no significant association with cancer risk as observed in allelic (T vs G: OR=1.024, 95%CI=0.954 to 1.099, p=0.508), homozygous (TT vs GG: OR=1.137, 95%CI=0.944 to 1.370, p=0.176), heterozygous (GT vs GG: 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/b polymorphism. Pooled results indicated no significant association under allelic (A vs B: OR=0.981, 95%CI=0.725 to 1.329, p=0.902), homozygous (AA vs BB: OR=1.166, 95%CI=0.524 to 2.593, p=0.707), heterozygous (BA vs BB: 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. This meta-analysis suggests that G894T and 4a/b polymorphisms of NOS3 gene are not associated with increased or decreased risk of overall cancer.




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