The Relationship Between eNOS Polymorphisms With Age, Smoking, Body Mass Index, and Clinicopathologic Parameters in Patients With Breast Cancer in Comparison With a Control Group.

INTRODUCTION

Nitric oxide (NO) is a free radical involved in carcinogenesis and is synthesized by endothelial nitric oxide synthase (eNOS). Genetic changes in the eNOS enzyme affect its activity, and the nitric oxide produced by inhibiting apoptosis can lead to cancer cell proliferation and metastasis. In this study, in addition to investigating the relationship between genetic changes in eNOS gene and the risk of breast cancer, the relationship between genotypes of polymorphisms, age, smoking, body mass index, and clinopathologic parameters was also investigated.

MATERIAL AND METHODS

Three functional (Intron 4a/b, T786C, and G894T) and 1 tagging (G10T) polymorphisms of the eNOS gene were examined in 203 patients with breast cancer and 203 control subjects, and their genotypes were identified by restriction fragment length polymorphism polymerase chain reaction.

RESULTS

The T allele in G10T polymorphism increased the risk of breast cancer by 1.503-fold, whereas allele a in Intron 4, T allele in G894T, and C allele in T786C decreased its risk by 0.678-, 0.440-, and 0.525-fold, respectively. GG, GT (G10T), bb and ab (Intron4), GG and TT (G894T), and TT and CC (T786C) genotypes were significantly correlated with body mass index. There was a significant relationship between age and bb genotype, cigarette smoking and genotype ab (Intron 4), and estrogen receptor and GG (G10T) genotype. Tumor invasion factor was also significantly associated with TT (G10T), bb (Intron 4), and TT (T786C) genotypes.

CONCLUSION

Genetic changes in eNOS appear to have a dual role in breast cancer rate owing to changes in NO production and can be introduced as one of the genetic markers involved in breast cancer by evaluating the genotype of different populations.