ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma

Abstract

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell RCC (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Fasting serum adiponectin was lower in subjects carrying minor alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.

Evolving role of adiponectin in cancer-controversies and update

“…However, a more recent study found a positive association between APN levels and RCC risk, which appeared to vary with ethnicity 130 . This may highlight the complicated picture presented by different APN multimers in RCC.…”

Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes

“…However, we did not observe such association in our datasets although the SNP was not directly genotyped (proxy: rs3751812, R 2 =0.99, data described in text only). Another study specifically assessed three genetic variants in the adiponectin gene ( ADIPOQ ) in a case-control study, and nominal significant association was found for rs182052 (12). Neither rs182052 nor good proxies were genotyped in the discovery phase.…”

“…According to a recent twin study, a great proportion of variation in kidney cancer risk can be explained by inter-individual genetic difference (heritability=38%, 95% CI= 21–55%) (10), which indicates that additional genetic susceptibility loci are remained to be identified for RCC. Previous studies have suggested RCC risk associations with genetic polymorphisms in obesity-related genes such as FTO (11), ADIPOQ (12), and genes in the mTOR signaling pathways (13). However, independent validations are largely missing in previous studies.…”

Serum Adiponectin Level May be an Independent Predictor of Clear Cell Renal Cell Carcinoma

“…It is also possible that sometimes the expression of adiponectin in adipose tissues is tumor guided, considering that inflammatory conditions may affect gene expression and the function of human adipose tissue-derived mesenchymal stem cells 27 . Conversely, results from a genome-wide association study (GWAS) identified an rs718314 in inositol 1, 4, 5-triphosphate receptor, type 2 (ITPR2) gene which is both associated with RCC cancer risk and Waist-to-Hip Ratio, reminding us that obesity and RCC may have a parallel cause 28 . Additionally, our research group previously reported that a single nucleotide polymorphism (rs182052) in the adiponectin gene is significantly associated with ccRCC risk 28 , indicating that patients with ccRCC may have distinctive adipose metabolic characteristics due to special genetic backgrounds.…”