title: Platelet Derived Growth Factor-B and Human Epidermal Growth Factor Receptor-2 Polymorphisms in Gall Bladder Cancer.
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 Ile655Val 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 Ile655Val (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.
authors: Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India E-mail : suraksha@sgpgi.ac.in, sur_ksha_agrawal@yahoo.co.in.
authors: Kumudesh
authors: K
authors: Mishra
authors: Anu
authors: A
authors: Behari
authors: Vinay Kumar
authors: VK
authors: Kapoor
authors: M Salman
authors: MS
authors: Khan
authors: Swayam
authors: S
authors: Prakash
authors: Suraksha
authors: S
authors: Agrawal
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D012307:Risk Factors
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D066246:ErbB Receptors