Rs401681 polymorphism in TERT-CLPTM1L was associated with bladder cancer risk: A meta-analysis

Document Type: Original Article


1 Anhui Medical University, Hefei, Anhui, China (230032)

2 BGI-Shenzhen, Shenzhen, China (518000)

3 Department of Anatomy, School of Basic Medicine Science, Southern Medical University, Guangzhou, China (510000)

4 Department of Urology, Zhujiang Hospital, Southern Medical University, China

5 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China (510000)


Objective(s):Genome-wide association studies have identified a number of genetic variants of telomerase reverse transcriptase (TERT), cleft lip and palate transmembrane1-like (CLPTM1L) associated with the risk of bladder cancer. Rs401681 polymorphism in TERT-CLPTM1L was of special interest for bladder cancer risk, whereas the results were inconclusive.
Materials and Methods:Publications illustrating the association between rs401681 polymorphism and bladder cancer risk were collected from the Embase, PubMed and Google scholar. Three independent reviewers worked on the data extraction. The meta-analysis was performed by STATA 12.0. The odds ratio (OR) with 95% confidence interval (CI) was calcu‌lated for these data.
Results: Six case-control studies were retrieved reporting a total of 9196 bladder cancer patients and 42570 controls. The strength of the relevance between rs401681 polymorphism and bladder cancer risk was evaluated by Stata 12.0 software. Rs401681[C] allele was identified marginally                  associated with increased bladder cancer risk, with per allele OR of 1.132 (95% CI=1.080-1.187, Pheterogeneity=0.701); in the stratified analysis by ethnicity, the increased cancer risk was revealed in Asian and Caucasian groups. Moreover, we also revealed that rs401681 polymorphism was associated with an increased risk of bladder cancer in Asian population with three publications under allele model (OR=3.722, 95% CI=1.311-10.568, P=0.014), whereas a decreased risk was identified in homozygote model (OR=0.692, 95 % CI=0.513-0.934, P= 0.016) and recessive model (OR=0.728, 95% CI=0.541-0.980, P=0.036).                            
Conclusion: In summary, our study provided evidence that rs401681 polymorphism is associated with the risk of bladder cancer.


1. Zhang Y, Sun Y, Chen T, Hu H, Xie W, Qiao Z, et al. Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Int J Mol Sci 2014; 15:19330-19341.

2. Cancer Genome Atlas Research N. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507:315-322.

3. Wu S, Huang P, Li C, Huang Y, Li X, Wang Y, et al. Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study. Eur Urol 2014; 65:274-277.

4. Muller M, Heicappell R, Krause H, Sachsinger J, Porsche C, Miller K. Telomerase activity in malignant and benign renal tumors. Eur Urol 1999; 35:249-255.

5. Chong L, van Steensel B, Broccoli D, Erdjument-Bromage H, Hanish J, Tempst P, et al. A human telomeric protein. Science 1995; 270:1663-1667.

6. Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 2009; 41:221-227.

7. Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet 2008; 40:1407-1409.

8. Gudmundsson J, Besenbacher S, Sulem P, Gudbjartsson DF, Olafsson I, Arinbjarnarson S, et al. Genetic correction of PSA values using sequence variants associated with PSA levels. Sci Translat Med 2010; 2:62ra92.

9. Gago-Dominguez M, Jiang X, Conti DV, Castelao JE, Stern MC, Cortessis VK, et al. Genetic variations on chromosomes 5p15 and 15q25 and bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study. Carcinogenesis 2011; 32:197-202.

10. Law MH, Montgomery GW, Brown KM, Martin NG, Mann GJ, Hayward NK, et al. Meta-analysis combining new and existing data sets confirms that the TERT-CLPTM1L locus influences melanoma risk.  J Invest Dermatol 2012; 132:485-487.

11. Pooley KA, Tyrer J, Shah M, Driver KE, Leyland J, Brown J, et al. No association between TERT-CLPTM1L single nucleotide polymorphism rs401681 and mean telomere length or cancer risk. Cancer Epidemiol Biomarkers Prev 2010; 19:1862-1865.

12. Ma Z, Hu Q, Chen Z, Tao S, Macnamara L, Kim ST, et al. Systematic evaluation of bladder cancer risk-associated single-nucleotide polymorphisms in a Chinese population. Mol Carcinog 2013; 52:916-921.

13. Rothman N, Garcia-Closas M, Chatterjee N, Malats N, Wu X, Figueroa JD, et al. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet 2010; 42:978-984.

14. Gu J, Wu X. Genetic susceptibility to bladder cancer risk and outcome. Per Med 2011; 8:365-374.

15. Li C, Yin Z, Wu W, Li X, Zhou B. Genetic variants in TERT-CLPTM1L genetic region associated with several types of cancer: a meta-analysis. Gene 2013; 526:390-399.