The association between the TERT rs2736100 AC genotype and reduced risk of upper tract urothelial carcinomas in a Han Chinese population
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Xiaotian Yuan1,4,*, Yan Meng2,*, Ping Li3, Nan Ge2, Feng Kong2,4, Liu Yang2,4, Magnus Björkholm1,4, Shengtian Zhao2,4, Dawei Xu1,4
1Department of Medicine, Division of Haematology and Centre for Molecular Medicine (CMM), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden
2Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China
3Nursing School, Shandong University, Jinan, China
4Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China
*These authors have contributed equally to this work
Shengtian Zhao, email: [email protected]
Yan Meng, email: [email protected]
Keywords: cancer risk, SNP, telomerase, TERT, urothelial cell carcinoma
Received: December 22, 2015 Accepted: February 16, 2016 Published: February 27, 2016
Upper tract urothelial carcinomas (UTUCs) are originated from urothelium, and consist of renal pelvic carcinomas (RPCs) and ureter carcinomas (UCs). Most UTUCs have already become invasive when diagnosed and there is thus a need to identify high-risk populations for preventive intervention. Recent evidence has accumulated supporting common single nucleotide polymorphisms (SNPs) to be associated with increased risk of various malignancies. However, little is known about susceptibility loci in relation to UTUC development. We genotyped telomerase reverse transcriptase (TERT) rs2736100 variants, the SNP associated with a risk of multiple-types of cancer, in patients with UTUC (n = 212) and evaluated the relationship between the rs2736100 and UTUC risk by comparing to 289 healthy controls. Neither AA nor CC genotypes differed significantly between cases and controls, while the AC-carriers were associated with a reduced risk of UTUC compared to the homozygous AA (OR = 0.583; 95% CI: 0.388 - 0.875; P = 0.012) or AA + CC genotypes (0.613; 95% CI: 0.428 - 0.879; P = 0.010). Further analyses showed that the AC variant conferred a lower risk for early stage UTUCs or those with a wt TERT promoter. When UTUCs were sub-grouped into UCs and RPCs, the AC genotype still predicts a significantly lower risk for UC (P = 0.045, OR = 0.597, 95% CI: 0.370 - 0.963), while at a border line significance for RPC (P = 0.055, OR = 0.597, 95% CI: 0.324 - 0.976). Collectively, the rs2736100 AC variant predicts a reduced risk to develop UTUC.
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