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http://dx.doi.org/10.7314/APJCP.2015.16.14.5647

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.14, 2015 , pp. 5647-5654 More about this Journal
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.
Keywords
Gallbladder cancer; HER2; PDGFB; single nucleotide polymorphisms;
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