Association of the Telomerase Reverse Transcriptase rs10069690 Polymorphism with the Risk, Age at Onset and Prognosis of Triple Negative Breast Cancer.

ABSTRACT

Telomerase reverse transcriptase (TERT) plays a key role in the maintenance of telomere DNA length. The rs10069690 single nucleotide variant, located in intron 4 of TERT, was found to be associated with telomere length and the risk of estrogen receptor-negative but not-positive breast cancer. This study aimed at analysis of the association of rs10069690 genotype and TERT expression with the risk, age at onset, prognosis, and clinically and molecularly relevant subtypes of breast cancer. Accordingly, rs10069690 was genotyped in a hospital-based case-control study of 403 female breast cancer patients and 246 female controls of a Central European (Austrian) study population, and the mRNA levels of TERT were quantified in 106 primary breast tumors using qRT-PCR. We found that in triple-negative breast cancer patients, the minor rs10069690 TT genotype tended to be associated with an increased breast cancer risk (OR, 1.87; 95% CI, 0.75-4.71; p = 0.155) and was significantly associated with 11.7 years younger age at breast cancer onset (p = 0.0002), whereas the CC genotype was associated with a poor brain metastasis-free survival (p = 0.009). Overall, our data show that the rs10069690 CC genotype and a high TERT expression tended to be associated with each other and with a poor prognosis. Our findings indicate a key role of rs10069690 in triple-negative breast cancer.