BACKGROUND: The rs2736100 single nucleotide polymorphism (SNP) is located in the 
intron 2 of human telomerase reverse transcriptase (hTERT) gene. Recent 
genome-wide association studies (GWAS) have consistently supported the strong 
association between this SNP and risk for multiple cancers. Given the important 
role of the hTERT gene and this SNP in cancer biology, we hypothesize that 
rs2736100 may also confer susceptibility to anti-cancer drug sensitivity. In 
this study we aim to investigate the correlation between the rs2736100 genotype 
and the responsiveness to anti-cancer agents in the NCI-60 cancer cell panel.
METHODS AND MATERIALS: The hTERT rs2736100 was genotyped in the NCI-60 cancer 
cell lines. The relative telomere length (RTL) of each cell line was quantified 
using real-time PCR. The genotype was then correlated with publically available 
drug sensitivity data of two agents with telomerase-inhibition activity: 
Geldanamycin (HSP90 inhibitor) and RHPS4/BRACO19 (G-quadruplex stabilizer) as 
well as additional 110 commonly used agents with established mechanism of 
action. The association between rs2736100 and mutation status of TP53 gene was 
also tested.
RESULTS: The C allele of the SNP was significantly correlated with increased 
sensitivity to RHPS4/BRACO19 with an additive effect (r = -0.35, p = 0.009) but 
not with Geldanamycin. The same allele was also significantly associated with 
sensitivity to antimitotic agents compared to other agents (p = 0.003). The 
highest correlation was observed between the SNP and paclitaxel (r = -0.36, p = 
0.005). The telomere length was neither associated with rs2736100 nor with 
sensitivity to anti-cancer agents. The C allele of rs2736100 was significantly 
associated with increased mutation rate in TP53 gene (p = 0.004).
CONCLUSION: Our data suggested that the cancer risk allele of hTERT rs2736100 
polymorphism may also affect the cancer cell response to both TERT inhibitor and 
anti-mitotic agents, which might be attributed to the elevated 
telomerase-independent activity of hTERT, as well as the increased risk for TP53 
gene mutagenesis conferred by the polymorphism. Detailed mechanisms need to be 
further investigated.