Abstract
BackgroundOne-carbon metabolism is the basement of nucleotide synthesis and the methylation of DNA linked to cancer risk. Variations in one-carbon metabolism genes are reported to affect the risk of many cancers, including renal cancer, but little knowledge about this mechanism is known in Chinese population.MethodsEach subject donated 5 mL venous blood after signing the agreement. The study was approved by the Institutional Review Board of the Nanjing Medical University, Nanjing, China. 18 SNPs in six one-carbon metabolism-related genes (CBS, MTHFR, MTR, MTRR, SHMT1, and TYMS) were genotyped in 859 clear cell renal cell carcinoma (ccRCC) patients and 1005 cancer-free controls by the Snapshot.ResultsStrong associations with ccRCC risk were observed for rs706209 (P = 0.006) in CBS and rs9332 (P = 0.027) in MTRR. Compared with those carrying none variant allele, individuals carrying one or more variant alleles in these two genes had a statistically significantly decreased risk of ccRCC [P = 0.001, adjusted odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.06–0.90]. In addition, patients carrying one or more variant alleles were more likely to develop localized stage disease (P = 0.002, adjusted OR = 1.37, 95%CI = 1.11–1.69) and well-differentiated ccRCC (P<0.001, adjusted OR = 1.42, 95%CI = 0.87–1.68). In the subgroup analysis, individuals carrying none variant allele in older group (P = 0.007, adjusted OR = 0.67, 95%CI = 0.49–0.91), male group (P = 0.007, adjusted OR = 0.71, 95%CI = 0.55–0.92), never smoking group (P = 0.002, adjusted OR = 0.68, 95%CI = 0.53–0.88) and never drinking group (P<0.001, adjusted OR = 0.68, 95%CI = 0.53–0.88) had an increased ccRCC risk.ConclusionsOur results suggest that the polymorphisms of the one-carbon metabolism-related genes are associated with ccRCC risk in Chinese population. Future population-based prospective studies are required to confirm the results.
Highlights
Renal cell carcinoma (RCC), one lethal urologic cancer accounting for 2% of all cancer deaths, is the third most common cancer of the genitourinary tract, just next to prostate and bladder cancer [1]
Our results suggest that the polymorphisms of the one-carbon metabolism-related genes are associated with clear cell renal cell carcinoma (ccRCC) risk in Chinese population
One-carbon metabolism refers to a system of interdependent metabolic pathways facilitating the transfer of one-carbon units, which are the basement of nucleotide synthesis and the methylation of DNA
Summary
Renal cell carcinoma (RCC), one lethal urologic cancer accounting for 2% of all cancer deaths, is the third most common cancer of the genitourinary tract, just next to prostate and bladder cancer [1]. One-carbon metabolism refers to a system of interdependent metabolic pathways facilitating the transfer of one-carbon units, which are the basement of nucleotide synthesis and the methylation of DNA. Methylation is responsible for gene expression control, chromatin structure stability and the maintenance of genomic stability. One-carbon metabolism is the basement of nucleotide synthesis and the methylation of DNA linked to cancer risk. Variations in one-carbon metabolism genes are reported to affect the risk of many cancers, including renal cancer, but little knowledge about this mechanism is known in Chinese population
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