Asieh Golozar1, Terri H Beaty2, Patti E Gravitt2, Ingo Ruczinski3, You-Lin Qiao4, Jin-Hu Fan4, Ti Ding5, Ze-Zhong Tang5, Arash Etemadi6, Nan Hu6, Paula L Hyland6, Lemin Wang6, Chaoyu Wang6, Sanford M Dawsey6, Neal D Freedman6, Christian C Abnet6, Alisa M Goldstein6, Philip R Taylor6. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: agolozar@jhu.edu. 2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 4. Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China. 5. Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China. 6. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
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.
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.
Authors: Daniel Vallböhmer; Jeffrey H Peters; Hidekazu Kuramochi; Daniel Oh; Dong Yang; Daisuke Shimizu; Steven R DeMeester; Jeffrey A Hagen; Parakrama T Chandrasoma; Kathleen D Danenberg; Peter V Danenberg; Tom R DeMeester Journal: Arch Surg Date: 2006-05
Authors: W J Blot; J Y Li; P R Taylor; W Guo; S Dawsey; G Q Wang; C S Yang; S F Zheng; M Gail; G Y Li Journal: J Natl Cancer Inst Date: 1993-09-15 Impact factor: 13.506
Authors: J Y Li; P R Taylor; B Li; S Dawsey; G Q Wang; A G Ershow; W Guo; S F Liu; C S Yang; Q Shen Journal: J Natl Cancer Inst Date: 1993-09-15 Impact factor: 13.506