TERT-CLPTM1L polymorphism rs401681 contributes to cancers risk: evidence from a meta-analysis based on 29 publications

Abstract

Background: Some common genetic variants of TERT-CLPTM1L gene, which encode key protein subunits of telomerase, have been suggested to play a crucial role in tumorigenesis. The TERT-CLPTM1L polymorphism rs401681 was of special interest for cancers risk but with inconclusive results.

Methodology/principal findings: We performed a comprehensive meta-analysis of 29 publications with a total of 91263 cases and 735952 controls. We assessed the strength of the association between rs401681 and overall cancers risk and performed subgroup analyses by cancer type, ethnicity, source of control, sample size and expected power. Rs401681 C allele was found to be associated with marginally increased cancers risk, with per allele OR of 1.04 (95%CI = 1.00-1.08, P(heterogeneity)<0.001) and an expected power of 1.000. Following further stratified analyses, the increased cancers risk were discovered in subgroups of lung, bladder, prostate, basal cell carcinomas and Asians, while a declined risk of pancreatic cancer and melanoma were detected.

Conclusions/significance: These findings suggested that rs401681 C allele was a low-penetrance risk allele for the development of cancers of lung, bladder, prostate and basal cell carcinoma, but a potential protective allele for melanoma and pancreatic cancer.

Figure 1. Literature search and study selection procedures for a meta-analysis of TERT-CLTPM1L polymorphism rs401681 and cancers risk.

Figure 2. ORs of overall cancer risks associated with rs401681 under the additive model by random effects.

For each data set, the OR and 95% CI was plotted with a box and a horizontal line. The symbol filled diamond indicates pooled OR and its 95% CI. Stacey1-3 represented studies for cancers of basal cell, squamous cell carcinomas and melanoma, respectively; Rafnar1-17 represented studies for basal cell, lung, bladder, prostate, cervical, breast, colorectal, melanoma, endometrial, kidney, lymphoma, multiple myeloma, ovarian, pancreatic, squamous cell, stomach and thyroid, respectively; Gago-Dominguez1-2 represented studies for bladder cancer in Caucasians and Asians, respectively; Pooley1-3 represented studies for breast, colorectal cancers and melanoma, respectively; Nan1-3 represented studies for melanoma, squamous cell and basal cell carcinomas, respectively.

Figure 3. Funnel plot analysis to detect publication bias for the TERT-CLMPT1L polymorphism rs401681 in the involved 52 data sets.