Abstract
Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.
Highlights
Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC)
Our study showed that subjects with a high total arsenic concentration in their urine had a high odds ratio (OR) for RCC8, even if they are exposed to low arsenic levels
Hypertension and diabetes were significantly associated with RCC with ORs of 2.76 (2.07–3.67) and 2.65 (1.80– 3.90), respectively
Summary
Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. Six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure. Chronic inflammation is a key player in the occurrence and development of RCC5 It can be caused by environmental exposure, obesity, tumorigenic pathogens, immune deregulation, and autoimmunity[6]. The aims of the study were to investigate the relationship between NLRP3 genotypes and the risk of RCC and explore whether NLRP3 gene polymorphisms could modify the risk between arsenic and RCC
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