Multiple genetic variants in telomere pathway genes and breast cancer risk

Jing Shen, Marilie D. Gammon, Hui Chen Wu, Mary Beth Terry, Qiao Wang, Patrick T. Bradshaw, Susan L. Teitelbaum, Alfred I. Neugut, Regina M. Santella

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Purpose: To explore the etiologic role of genetic variants in telomere pathway genes and breast cancer risk. Methods: A population-based case-control study, the Long Island Breast Cancer Study Project, was conducted, and 1,067 cases and 1,110 controls were included in the present study. Fifty-two genetic variants of nine telomere-related genes were genotyped. Results: Seven single nucleotide polymorphisms (SNP) showed significant case-control differences at the level of P < 0.05. The top three statistically significant SNPs under a dominant model were TERT-07 (rs2736109), TERT-54 (rs3816659), and POT1-03 (rs33964002). The odds ratios (OR) were 1.56 [95% confidence interval (95% CI), 1.22-1.99] for the TERT-07 G-allele, 1.27 (95% CI, 1.05-1.52) for the TERT-54 T-allele, and 0.79 (95% CI, 0.67-0.95) for the POT1-03 A-allele. TERT-67 (rs2853669) was statistically significant under a recessive model; theORof the CCgenotype was 0.69 (95% CI, 0.69-0.93) compared with the T-allele. However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P < 0.001 (0.05/52) except for TERT-07. When restricted to Caucasians (94% of the study subjects), a stronger association for the TERT-07 G-allele was observed with an OR of 1.60 (95% CI, 1.24-2.05; P = 0.0002). No effect modifications were found for variant alleles and menopausal status, telomere length, cigarette smoking, body mass index status, and family history of breast cancer risk. Conclusions: Four SNPs in the TERT and POT1 genes were significantly related with overall breast cancer risk. This initial analysis provides valuable clues for further exploration of the biological role of telomere pathway genes in breast cancer.

Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Issue number1
StatePublished - Jan 2010


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