Genetic variation in the ADIPOQ gene and serum adiponectin increase the risk of bladder cancer.

Abstract

Bladder cancer (BC) is the 10th most common cancer worldwide. Genetic studies estimated 30% heritability in BC risk. Adiponectin is an adipocytokine that has important roles in the regulation of energy metabolism. Recent evidence suggests dysregulation of adiponectin levels in BC tissues. Serum level of adiponectin is influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. However, limited evidence is available regarding the association between adiponectin serum levels or SNPs in ADIPOQ and BC risk. This study aimed to assess whether adiponectin serum levels or SNPs in ADIPOQ may modify BC risk. In this case-control study, 114 BC patients were recruited along with 114 controls. Study subjects were genotyped for variations in ADIPOQ SNPs, namely rs17300539, rs266729, rs2241766, and rs1501299. Adiponectin levels were measured from the serum of study subjects. Our analysis showed that the G allele and the GG genotype of rs1501299 were significantly more frequent in BC patients compared to those in the control group (p-value < 0.05). Moreover, two ADIPOQ haplotypes containing the above G allele were associated with increased BC risk (p-value < 0.05). Multivariate analysis showed that increased serum adiponectin, smoking or age were all significant predictors of BC (p-value < 0.05). The data supports use of serum adiponectin and the G allele of rs1501299 SNP in ADIPOQ as potential biomarkers and/or targets in BC. To further validate findings in this study, larger populations of various ethnicities and/or genetic backgrounds are required. More investigations on the functional role of adiponectin in BC will also provide better understanding of potential targeting adiponectin for BC treatment.