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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3′UTRA>G) 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 genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3′UTRA>G polymorphisms, C-826G 3′UTR and T-826A3′UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3′UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to '0' risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients. Conclusion: TNFA-308 and NFKBIA (-826C>T and 3′UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.

Original languageEnglish
Article numbere81999
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - 4 Dec 2013
Externally publishedYes

Fingerprint

squamous cell carcinoma
Polymorphism
prognosis
genetic polymorphism
Genotype
genotype
tumor necrosis factor-alpha
Epithelial Cells
Esophageal Squamous Cell Carcinoma
Tumor Necrosis Factor-alpha
Genes
neoplasms
risk reduction
Risk analysis
Survival Analysis
nationalities and ethnic groups
metastasis
Restriction Fragment Length Polymorphisms
carcinogenesis
Haplotypes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of esophageal squamous cell carcinoma. / Umar, Meenakshi; Upadhyay, Rohit; Kumar, Shaleen; Ghoshal, Uday Chand; Mittal, Balraj.

In: PLoS One, Vol. 8, No. 12, e81999, 04.12.2013.

Research output: Contribution to journalArticle

Umar, Meenakshi ; Upadhyay, Rohit ; Kumar, Shaleen ; Ghoshal, Uday Chand ; Mittal, Balraj. / Association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of esophageal squamous cell carcinoma. In: PLoS One. 2013 ; Vol. 8, No. 12.
@article{6dc33b13f34d4cd49a21cd7f6cc591fe,
title = "Association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of esophageal squamous cell carcinoma",
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 -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3′UTRA>G) 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 genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3′UTRA>G polymorphisms, C-826G 3′UTR and T-826A3′UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3′UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to '0' risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients. Conclusion: TNFA-308 and NFKBIA (-826C>T and 3′UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.",
author = "Meenakshi Umar and Rohit Upadhyay and Shaleen Kumar and Ghoshal, {Uday Chand} and Balraj Mittal",
year = "2013",
month = "12",
day = "4",
doi = "10.1371/journal.pone.0081999",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of esophageal squamous cell carcinoma

AU - Umar, Meenakshi

AU - Upadhyay, Rohit

AU - Kumar, Shaleen

AU - Ghoshal, Uday Chand

AU - Mittal, Balraj

PY - 2013/12/4

Y1 - 2013/12/4

N2 - 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 -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3′UTRA>G) 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 genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3′UTRA>G polymorphisms, C-826G 3′UTR and T-826A3′UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3′UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to '0' risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients. Conclusion: TNFA-308 and NFKBIA (-826C>T and 3′UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.

AB - 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 -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3′UTRA>G) 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 genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3′UTRA>G polymorphisms, C-826G 3′UTR and T-826A3′UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3′UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to '0' risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients. Conclusion: TNFA-308 and NFKBIA (-826C>T and 3′UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.

UR - http://www.scopus.com/inward/record.url?scp=84891897522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891897522&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0081999

DO - 10.1371/journal.pone.0081999

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e81999

ER -