A functional promoter polymorphism in the TERT gene does not affect inherited susceptibility to breast cancer.

Telomere dysfunction is a key mechanism in cancer development. The human telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of the telomerase enzyme, which is necessary for the maintenance of telomere DNA length, chromosomal stability, and cellular immortality. In our attempt to identify functional polymorphisms in the TERT gene and their effect on breast cancer risk, we sequenced the promoter of the gene and identified three single nucleotide polymorphisms (SNPs) with a frequency of at least 10%. One of these SNPs, rs2853669 (—244 T > C), has been shown to affect telomerase activity and telomere length. Recently, this SNP has been suggested to affect familial breast cancer risk. In our case–control study using two large breast cancer sample series, including one with 841 cases with inherited susceptibility to breast cancer, we did not find any association with familial or sporadic breast cancer risk. This well-powered study excludes an effect of the functional —244 T > C SNP and two other correlated SNPs on breast cancer risk.