Impact of vascular endothelial growth factor gene-gene and gene-smoking interaction and haplotype combination on bladder cancer risk in Chinese population

Abstract

AimsTo investigate the association of single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) gene polymorphisms, additional gene- gene and gene- smoking interactions with bladder cancer risk.ResultsBladder cancer risk was significantly higher in carriers of the rs699947- A allele within VEGF gene than those with rs699947- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.70 (1.16–2.31), and higher in carriers of the rs833052- A allele of within VEGF gene than those with rs833052- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.65 (1.23–2.12). GMDR analysis indicated a potential interaction between rs2010963 and smoking on bladder cancer risk. Current smokers with rs2010963- GC+CC genotype within VEGF gene have the highest bladder cancer risk, compared to never smokers with rs2010963- GG genotype within VEGF gene, OR (95%CI) = 3.25 (1.71–4.83). Haplotype containing the rs2010963- C and rs833052- A alleles were associated with a statistically increased bladder cancer risk, OR (95%CI) = 2.21 (1.12–3.42).Materials and MethodsGeneralized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association of 6 SNPs within VEGF gene, additional gene- gene and gene- smoking interaction with bladder cancer risk.ConclusionsWe found that the A allele of rs699947 and the A allele of rs833052 within VEGF gene, interaction between rs2010963 and smoking, haplotype containing the rs2010963- C and rs833052- A alleles were all associated with increased bladder cancer risk.

Haplotype‐based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population

“…Furthermore, other contrasting results were reported; Ruhi Kapahi found a significant increase of AA genotype frequency in patients with breast cancer disease with 2.87‐fold risk . Same risk associations were reported with cervical cancer, thyroid carcinoma, bladder cancer, and breast cancer risk . But it's noteworthy that others studies failed to found any significant associations with different cancer type including gastric, bladder breast, renal, and Gallbladder cancer .…”

“…Considering +936C/T SNP, it's always reported to be in weak LD with both ‐2578C/A and ‐2549I/D polymorphisms …”

“…The linkage disequilibrium test showed a strong LD associations between -2578C/A and -2549I/D polymorphisms with (D'=0.94, Considering +936C/T SNP, it's always reported to be in weak LD with both -2578C/A and -2549I/D polymorphisms. 25 The reason for these discrepancies remains unclear. These could Firstly, this is a hospital-based case-control study, so the selection bias may not be avoidable and the subjects may not be representative of the general population.…”

Association of Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms With Gastric Cancer and Its Development, Prognosis, and Survival

“… 4 Vascular endothelial growth factor is known as a lymphangiogenic growth factor and plays an important role in tumor lymphangiogenesis via activation of the VEGF receptor. 5 Present data indicate that VEGF gene polymorphisms were associated with the risk of cancers, such as bladder cancer, 6 papillary thyroid carcinoma, 7 lung cancer, 8 hepatocellular carcinoma, 9 and renal cell carcinoma. 10 The VEGF pathway also plays a prominent role in the growth and progression of human cancer, including gastric cancer.…”

Molecular Markers of VEGF, TNF--α and TNF- β in Patients with Bladder Cancer in Stage T3N0M0 and their Relationship with the Degree of Tumor Neoplasia

“…Одним з основних факторів виживання і поширення пухлинних клітин є ангіогенез. На даний момент, накопичено безліч даних, що підтверджують участь VEGF (фактор росту ендотелію судин) і TNF (фактор некрозу пухлини), відповідальних за мітогенну активність клітин, у розвитку та прогресуванні злоякісних новоутворень і, отже, є перспективними мішенями при використанні таргетної терапії [2,3,4].…”