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Polymorphism of Growth Factors and Survival in Gall Bladder Cancer
Vinay K. Kapoor*1, Kumudesh Mishra1, Anu Behari1, Salman Khan2, Suraksha Agrawal3
1Surgical Gastroenterology, SGPGIMS, Lucknow, UP, India; 2Biosciences, Integral University, Lucknow, India; 3Medical Genetics, SGPGIMS, Lucknow, India
Gall bladder cancer (GBC) is the commonest biliary tract cancer worldwide and the commonest gastrointestinal cancer in women in north India. Angiogenesis plays an important role in progression of cancer. Growth factors and their receptors are involved in tumor angiogenesis. Vascular endothelial factor (VEGF), platelet derived growth factor-B (PDGFB) and human epidermal growth factor receptor-2 (HER2) belong to the family of tyrosine kinase receptors. We evaluated the role of single nucleotide polymorphisms (SNPs) of VEGF, PDGFB and HER2 genes in survival of patients with GBC.
VEGF -1154 G>A and -2578 C>A, PDGFB +286 A>G and +1135 A>C polymorphisms were studied by amplification refractory mutation system (ARMS) polymerase chain reaction (PCR), VEGF +936 C>T and HER2 Ile635Val polymorphism by restriction fragment length polymorphism (RFLP) and VEGF -2549 Ins/Del by PCR in DNA extracted from the venous blood from 80 patients with GBC (stage I+II =35, stage III+IV = 45) who were operated before 2010 (to ensure at least 5 years follow up) and in whom follow up data were available.
Overall survival in 80 patients was mean 32.7+6.7 months and median 19.0+3.3 months. There was no association of VEGF, PDGFB and HER2 SNPs with stage (tumor depth, nodal spread and distant metastases). VEGF genotypes +936 CC and -1154 GA and PDGFB genotype +1135 AA showed significantly longer survival (Table); there was no correlation of survival with HER2 polymorphism.
VEGF and PDGFB polymorphisms may affect survival in GBC.
Growth factors polymorphisms and survival in gall bladder cancer (n=80)
| | | Survival | Survival | | | Growth factor | Genotype (no. of cases) | Mean+SE (95% CI) | Median+SE (95% CI) | p value | | VEGF+936 C>T | TT (n=11) | 14.0+4.5 (5.0-23.1) | 8.0+3.8 (0.4-15.5) | 0.026 | | | CT (n=20) | 18.4+3.9 (10.6-26.1) | 11.0+2.2 (6.6-15.3) | | | | CC (n=49) | 44.3+11.2 (22.3-66.2) | 24.0+3.4 (17.1-30.8) | | | VEGF-1154 G>A | AA (n=7) | 8.1+2.7 (2.7-13.5) | 7.0+2.6 (1.8-12.1) | 0.006 | | | GA (n=27) | 45.3+11.4 (22.9-67.7) | 30.0+4.3 (21.5-38.4) | | | | GG (n=46) | 20.7+2.9 (14.9-26.5) | 11.0+4.2 (2.7-19.3) | | | PDGF+1135 A>C | CC (n=39) | 22.7+7.0 (8.8-36.6) | 10.0+5.6 (0.0-21.0) | 0.024 | | | CA (n=28) | 25.4+3.5 (18.5-32.3) | 25.0+6.5 (12.0-37.9) | | | | AA (n=13) | 46.8+11.5 (24.2-69.5) | 30.0+9.8 (10.6-49.3) | |
 Survival curves
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