Functional Genetic Variants in SPHK1 Affect Susceptibility to Gastric Cancer in a Chinese Population.

Abstract

An escalating number of studies have provided identified evidence that sphingosine kinase 1 (SPHK1) plays an essential role in carcinogenesis. This present study was devised to seek the possible correlation of two tag single-nucleotide polymorphisms (SNPs) in SPHK1 (rs3744037 T>C, rs346801 C>T) with the susceptibility to gastric cancer (GC). This present case-control study was comprised of 710 patients with GC and 710 gender- and age-matched cancer-free individuals. The genotypes of the individuals were acquired by the TaqMan-MGB method. SPHK1 mRNA level was examined in 60 paired cancerous and noncancerous tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Our results suggested that the variant genotype T allele of SPHK1 rs346801 increased the GC risk in the study population [CT vs. CC, odds ratio (OR) = 1.385, 95% confidence interval (CI) = 1.096 - 1.751; TT vs. CC, OR = 2.502, 95% CI = 1.078 - 5.806; CT+TT vs. CC, OR = 1.434, 95% CI = 1.140 - 1.804]. Furthermore, in stratified analyses, rs346801 variant genotypes were associated with a conspicuous risk of GC in younger individuals (< 62 years), females, non-smokers, and individuals from rural areas. In addition, the carriers with variant genotype CT, TT, and CT+TT were observed to possess the higher SPHK1 messenger RNA levels than those with CC genotype in GC specimens. These results strongly demonstrated that the SPHK1 rs346801 C>T polymorphism may contribute to the susceptibility to gastric cancer in Chinese population and affect the expression of SPHK1 and, therefore, may act as a novel biomarker for predicting gastric cancer.