Breast Cancer: Targets and Therapy (Jan 2017)
Association between telomere length and CYP19 TTTA repetition polymorphism in healthy and breast cancer-diagnosed women
Abstract
Blanca Murillo-Ortiz,1 Sandra Martínez-Garza,1 David Suárez García,1 Rosa del Carmen Castillo Valenzuela,2 Juan Francisco García Regalado,2 Gerardo Cano Velázquez1 1Institute Mexican of Social Security, Department Oncology, Unit of Research in Clinical Epidemiology, 2Department of Medical Sciences, University of Guanajuato, León Guanajuato, Mexico Introduction: Several studies have reported an increase in breast cancer (BC) risk when patients are carriers of the CYP19 TTA polymorphism with ≥10 repeats; moreover, it has been reported that telomere length is associated with a higher susceptibility of developing cancer. Objective: The objective of this study was to understand the relationship between CYP19 TTTA repetition polymorphism and telomere length and its effects on serum estradiol, estrone and follicle-stimulating hormone (FSH). Materials and methods: A total of 180 postmenopausal healthy and 70 BC-diagnosed women were included. Telomere length was determined through real-time quantitative polymerase chain reaction, and aromatase polymorphism was analyzed through DNA; both samples were obtained from circulating leukocytes. Serum estrone, estradiol and FSH were determined by enzyme-linked immunosorbent assay. Results: Patients with a BC diagnosis showed >10 repetitions more frequently, compared with that of healthy women (50% vs 23%, Χ2 =11.44, p=0.0007). A significant difference in telomere length between healthy and BC women was observed (5,042.7 vs 2,256.7 pb, Z=4.88, p<0.001). CYP19 TTTA repeat polymorphism was associated with serum levels of estradiol and estrone in both groups, being higher in those with >10 repeats. Moreover, telomere length showed an inverse relationship with the number of repeats of the aromatase polymorphism in healthy women (R2=0.04, r= -0.24); in contrast, BC patients did not display this relationship. In addition, telomere length presented an inverse relationship with serum levels of estradiol and estrone in BC patients (p=0.02). Conclusion: Telomere length is shorter in BC patients than in healthy patients. The CYP19 TTTA repeat polymorphism is associated with serum levels of estradiol and estrone in both healthy women and BC patients, being higher in those with polymorphism carriers >10 repeats. Telomere length has an inverse correlation with the number of repeats of the aromatase polymorphism in healthy women but not in BC women. Estradiol and estrone levels in BC women have an inverse relationship with telomere length. Keywords: telomere length, CYP19 polymorphism, breast cancer
