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

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Telomere maintenance is crucial for cell stability, with telomerase reverse transcriptase (TERT) playing a central role.
• The TERT rs10069690 single nucleotide variant has been implicated in telomere length regulation and breast cancer risk, particularly in estrogen receptor-negative subtypes.
• Understanding genetic contributions to breast cancer subtypes is vital for improving diagnostics and treatment strategies.

Purpose of the Study:

• To investigate the association between the TERT rs10069690 genotype and TERT expression with breast cancer risk, age at onset, and prognosis.
• To analyze these associations across different clinically and molecularly relevant breast cancer subtypes.
• To elucidate the specific role of the rs10069690 variant in triple-negative breast cancer.

Main Methods:

• A hospital-based case-control study was conducted with 403 female breast cancer patients and 246 female controls from Austria.
• Genotyping for the rs10069690 single nucleotide variant was performed.
• Telomerase reverse transcriptase (TERT) mRNA levels were quantified in 106 primary breast tumors using quantitative reverse transcription PCR (qRT-PCR).

Main Results:

• In triple-negative breast cancer patients, the minor rs10069690 TT genotype showed a trend towards increased risk (OR, 1.87) and was significantly associated with an earlier age of onset (11.7 years younger, p=0.0002).
• The rs10069690 CC genotype was linked to poorer brain metastasis-free survival (p=0.009).
• A correlation was observed between the rs10069690 CC genotype, high TERT expression, and unfavorable prognosis.

Conclusions:

• The TERT rs10069690 variant plays a significant role in the development and progression of triple-negative breast cancer.
• Genotype rs10069690 influences TERT expression and is associated with key clinical parameters like age at onset and survival outcomes.
• These findings underscore the importance of TERT genetics in understanding aggressive breast cancer subtypes.