title: Genetic variation in five genes important in telomere biology and risk for breast cancer.
abstract: Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C>T, -244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies.
authors.affiliation: Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. savagesh@mail.nih.gov
authors.forename: S A
authors.initials: SA
authors.lastname: Savage
authors.forename: S J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: J
authors.initials: J
authors.lastname: Lissowska
authors.forename: L A
authors.initials: LA
authors.lastname: Brinton
authors.forename: D
authors.initials: D
authors.lastname: Richesson
authors.forename: B
authors.initials: B
authors.lastname: Peplonska
authors.forename: A
authors.initials: A
authors.lastname: Bardin-Mikolajczak
authors.forename: W
authors.initials: W
authors.lastname: Zatonski
authors.forename: N
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: M
authors.initials: M
authors.lastname: Garcia-Closas
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D004273:DNA, Neoplasm; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins; D018570:Risk Assessment; D012307:Risk Factors; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2
chemical_list: D002352:Carrier Proteins; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; C440849:POT1 protein, human; D016601:RNA-Binding Proteins; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins; C104342:TEP1 protein, human; C059329:TERF1 protein, human; C504753:TERF2 protein, human; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; C509186:TERT protein, human; D019098:Telomerase