Oesophageal squamous cell carcinoma in high-risk Chinese populations: Possible role for vascular epithelial growth factor A

Asieh Golozar, Terri H. Beaty, Patti E. Gravitt, Ingo Ruczinski, You Lin Qiao, Jin Hu Fan, Ti Ding, Ze Zhong Tang, Arash Etemadi, Nan Hu, Paula L. Hyland, Lemin Wang, Chaoyu Wang, Sanford M. Dawsey, Neal D. Freedman, Christian C. Abnet, Alisa M. Goldstein, Philip R. Taylor

Research output: Contribution to journalArticle

Abstract

Background Mechanisms involved in wound healing play some role in carcinogenesis in multiple organs, likely by creating a chronic inflammatory milieu. This study sought to assess the role of genetic markers in selected inflammation-related genes involved in wound healing (interleukin (IL)-1a, IL-1b, IL-1 Receptor type I (IL-1Ra), IL-1 Receptor type II (IL-1Rb), tumour necrosis factor (TNF)-α, tumour necrosis factor receptor superfamily member (TNFRSF)1A, nuclear factor kappa beta (NF-kB)1, NF-kB2, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, hypoxia induced factor (HIF)-1α, vascular endothelial growth factor (VEGF)A and P-53) in risk to oesophageal squamous cell carcinoma (OSCC). Methods We genotyped 125 tag single nucleotide polymorphism (SNP)s in 410 cases and 377 age and sex matched disease-free individuals from Nutritional Intervention Trial (NIT) cohort, and 546 cases and 556 controls individually matched for age, sex and neighbourhood from Shanxi case-control study, both conducted in high-risk areas of north-central China (1985-2007). Cox proportional-hazard models and conditional logistic regression models were used for SNPs analyses for NIT and Shanxi, respectively. Fisher's inverse test statistics were used to obtain gene-level significance. Results Multiple SNPs were significantly associated with OSCC in both studies, however, none retained their significance after a conservative Bonferroni adjustment. Empiric p-values for tag SNPs in VEGFA in NIT were highly concentrated in the lower tail of the distribution, suggesting this gene may be influencing risk. Permutation tests confirmed the significance of this pattern. At the gene level, VEGFA yielded an empiric significance (P = 0.027) in NIT. We also observed some evidence for interaction between environmental factors and some VEGFA tag SNPs. Conclusion Our finding adds further evidence for a potential role for markers in the VEGFA gene in the development and progression of early precancerous lesions of oesophagus.

Original languageEnglish (US)
Pages (from-to)2855-2865
Number of pages11
JournalEuropean Journal of Cancer
Volume50
Issue number16
DOIs
StatePublished - Nov 2014

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Keywords

  • Genetic marker
  • Genetics
  • Inflammation
  • Inflammation-related events
  • Keywords Oesophageal squamous cell carcinoma
  • VEGFA
  • Vascular endothelial growth factor A
  • Wound-healing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Golozar, A., Beaty, T. H., Gravitt, P. E., Ruczinski, I., Qiao, Y. L., Fan, J. H., Ding, T., Tang, Z. Z., Etemadi, A., Hu, N., Hyland, P. L., Wang, L., Wang, C., Dawsey, S. M., Freedman, N. D., Abnet, C. C., Goldstein, A. M., & Taylor, P. R. (2014). Oesophageal squamous cell carcinoma in high-risk Chinese populations: Possible role for vascular epithelial growth factor A. European Journal of Cancer, 50(16), 2855-2865. https://doi.org/10.1016/j.ejca.2014.07.022