title: The association between the TERT rs2736100 AC genotype and reduced risk of upper tract urothelial carcinomas in a Han Chinese population.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Haematology and Centre for Molecular Medicine (CMM), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.|Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Nursing School, Shandong University, Jinan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ge
authors.affiliation: Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China.|Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China.|Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Medicine, Division of Haematology and Centre for Molecular Medicine (CMM), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.|Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China.
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: Department of Urology and Central Research Laboratory, Shandong University Second Hospital, Jinan, China.|Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China.
authors.forename: Shengtian
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Division of Haematology and Centre for Molecular Medicine (CMM), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.|Karolinska Institutet-Shandong University Collaborative Laboratories for Cancer and Stem Cell Research, Jinan, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D065840:Protective Factors; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D014516:Ureteral Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: SNP; TERT; cancer risk; telomerase; urothelial cell carcinoma