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Platelet Derived Growth Factor-B and Human Epidermal Growth Factor Receptor-2 Polymorphisms in Gall Bladder Cancer

  • Mishra, Kumudesh (Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences) ;
  • Behari, Anu (Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences) ;
  • Kapoor, Vinay Kumar (Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences) ;
  • Khan, M. Salman (Department of Biosciences, Integral University) ;
  • Prakash, Swayam (Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences) ;
  • Agrawal, Suraksha (Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences)
  • Published : 2015.09.02

Abstract

Gall bladder cancer (GBC) is a gastro-intestinal cancer with high prevalence among north Indian women. Platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) may play roles in the etiology of GBC through the inflammation-hyperplasia-dysplasia-carcinoma pathway. To study the association of PDGFB and HER2 polymorphisms with risk of GBC, 200 cases and 300 controls were considered. PDGFB +286A>G and +1135A>C polymorphisms were investigated with an amplification refractory mutation system and the HER2 $Ile^{655}Val$ polymorphism by restriction fragment length polymorphism. Significant risk associations for PDGFB +286 GG (OR=5.25) and PDGFB +1135 CC (OR=3.19) genotypes were observed for GBC. Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2 $Ile^{655}Val$ (OR=2.52) polymorphisms among female GBC cases. GBC cases with gall stones were predisposed to homozygous +286 GG and +1135 CC genotypes. Significant risk associations were found for ACIle (OR=1.48), GAVal (OR=1.70), GAIle (OR=2.00) haplotypes with GBC cases and GCIle haplotype with female GBC cases (OR=10.37, P=<0.0001). Pair-wise linkage disequilibrium revealed negative associations among variant alleles. On multi-dimensional reduction analysis, a three factor model revealed significant gene-gene interaction for PDGFB +286A>G, PDGFB +1135A>C and HER2 Ile165Val SNPs with GBC. Protein-protein interaction showed significant association of PDGFB and HER2 with the epidermal growth factor receptor signaling pathway.

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