Association of Common Polymorphisms in TNFA, NFkB1 and NFKBIA with Risk and Prognosis of Esophageal Squamous Cell Carcinoma.docVIP

Association of Common Polymorphisms in TNFA, NFkB1 and NFKBIA with Risk and Prognosis of Esophageal Squamous Cell Carcinoma Meenakshi Umar , Rohit Upadhyay , Shaleen Kumar , Uday Chand Ghoshal , Balraj Mittal 1 1¤ 2 3 1* 1 Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, 2 Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, 3 Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Abstract Background: Tumour necrosis factor-alpha (TNF-α) and nuclear factor of kappa light chain gene enhancer in activated B cells (NF-κB) play critical role in carcinogenesis processes like tumour initiation, proliferation, migration and invasion. Single nucleotide polymorphisms in TNF-α, NF-κB and its inhibitor IκB genes were shown to be associated with susceptibility and prognosis of several cancers; however, their role in esophageal squamous cell carcinoma (ESCC) is not well recognised. Therefore, in present study, we aimed to investigate association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of ESCC in northern Indian population. Methods: We genotyped 290 ESCC patients (including 162 followed up cases) and 311 mean age, gender and ethnicity matched controls for TNFA -308GA, NFkB1 -94ATTG ins/del and NFKBIA (-826CT and 3’UTRAG) polymorphisms using PCR alone or followed by RFLP and TaqMan assay. Results: TNFA -308GA genotype was associated with increased risk of ESCC specifically in females and in patients with regional lymph node involvement, while, NFKBIA -826CT+TT gen