Telomere Length-related Genetic Variants Contribute To The Risk Of Esophageal Squamous Cell Carcinoma In Chinese Populations

Background and purpose:Human telomeres, consisting of TTAGGG repetitive sequences and some biding proteins, locate at the ends of chromosomes. In normal cells, telomeres would shorten gradually with cell replication. When telomeres shorten to the critical length, these normal cells woule undergo senescence or apoptosis. A single nucleotide polymorphism (SNP) is a single base variation with a frequency of more than1%in at least one population. In the genome, about90%of human variation is based on SNPs. A previous genome wide association stydy (GWAS) demonstrated that rs398652on14q21and rs621559on1p34.2were associated with telomere length in Caucasians. In addition, short telomere length has been associated with significantly increased cancer risk. However, the role of rs398652or rs621559on esophageal squamous cell carcinoma (ESCC) susceptibility is still unknown. Therefore, we investigated whether these polymorphisms have impact on telomere length and the risk of ESCC in Chinese populations.Methods:In this study, we screened1,550patients with ESCC and gender-and age-matched1,620controls. The blood genomic DNAs were extracted with commercial kits. rs398652or rs621559were genotyped in1,550patients with ESCC and1,620controls. Genotypes of these genetic polymorphisms were examined using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). The associations between rs398652or rs621559genotypes and ESCC risk were computed by the logistic regression model with SPSS software. According to genotyping results, telomere length was measured by quantitave real-time PCR with genomic DNA of550controls. Linear regression was conducted to analyze the association of the telomere length with the SNPs.Results and conclusions:After genotyping1,550ESCC patients and frequency-matched1,620controls, we found that increased risk of ESCC is associated with the rs398652G allele and the rs621559A allele significantly decreases ESCC risk. It has been shown that both rs398652and rs621559polymorphisms were significantly associated with ESCC risk in additive, recessive or dominant genetic models. On the basic of measuring telomere length of550healthy individuals, we observed that both rs398652and rs621559genetic variants are significantly associated with telomere length. Our results highlight the complexity of genetic regulation of telomere length and further support the important role of telomere in carcinogenesis.