Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma
Journal
Scientific Reports
Journal Volume
10
Journal Issue
1
Pages
6640
Date Issued
2020
Author(s)
Chung C.-J.
Bao B.-Y.
Lin Y.-C.
Huang Y.-L.
Shiue H.-S.
Ao P.-L.
Hsueh Y.-M.
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. ? 2020, The Author(s).
SDGs
Other Subjects
arsenic; cryopyrin; NLRP3 protein, human; allele; case control study; female; gene expression; gene frequency; genetic predisposition; genetics; haplotype; human; inflammation; kidney tumor; male; metabolism; middle aged; odds ratio; pathology; renal cell carcinoma; risk assessment; risk factor; single nucleotide polymorphism; urine; Alleles; Arsenic; Carcinoma, Renal Cell; Case-Control Studies; Female; Gene Expression; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Humans; Inflammation; Kidney Neoplasms; Male; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Odds Ratio; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors
Publisher
Nature Research
Type
journal article