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

Mishra, Kumudesh; Behari, Anu; Kapoor, Vinay Kumar; Khan, M. Salman; Prakash, Swayam; Agrawal, Suraksha

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자료유형: 학술저널

저자정보: 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)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제14호

발행연도: 2015.1

수록면: 5,647 - 5,654 (8page)

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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.

#Gallbladder cancer #HER2 #PDGFB #single nucleotide polymorphisms

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Mishra, Kumudesh

소속기관 Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences