title: Multiple genetic variants in telomere pathway genes and breast cancer risk.
abstract: OBJECTIVE
  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; the OR of the CC genotype 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.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168th Street, P&S 19-418, New York, NY 10032, USA. js2182@columbia.edu
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Wu
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000089804:Shelterin Complex; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins