title: Telomere length and genetic variation in telomere maintenance genes in relation to ovarian cancer risk.
abstract: BACKGROUND
  Telomeres protect chromosomal ends, shorten with cellular division, and signal cellular senescence, but unchecked telomere attrition can lead to telomere dysfunction, upregulation of telomerase, and carcinogenesis. Shorter telomeres in peripheral blood leukocytes (PBL) have been associated with elevated cancer risk. Furthermore, genetic variants in and around the TERT gene have been implicated in carcinogenesis.
  
  
  METHODS
  We measured relative telomere length (RTL) in PBLs of 911 cases and 948 controls from the New England case-control (NECC) study, a population-based study of ovarian cancer. In addition, we assessed germ line genetic variation in five telomere maintenance genes among 2,112 cases and 2,456 controls from the NECC study and the Nurses' Health Study, a prospective cohort study. ORs and 95% CIs were estimated by logistic regression.
  
  
  RESULTS
  Overall, we observed no differences in telomere length between cases and controls. Compared with women with RTL in the longest tertile, women with RTL in the shortest tertile had no increase in risk (OR = 1.01, 95% CI: 0.80-1.28). However, several SNPs in the TERT gene, including rs2736122, rs4246742, rs4975605, rs10069690, rs2736100, rs2853676, and rs7726159, were significantly associated with ovarian cancer risk. We observed a significant gene-level association between TERT and ovarian cancer risk (P = 0.00008).
  
  
  CONCLUSIONS
  Our observations suggest that genetic variation in the TERT gene may influence ovarian cancer risk, but the association between average telomere length in PBLs and ovarian cancer remains unclear.
  
  
  CONCLUSIONS
  The role of telomeres in ovarian carcinogenesis remains unsettled and warrants further investigation.
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. kterry@partners.org
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Allison F
authors.initials: AF
authors.lastname: Vitonis
authors.forename: Jason
authors.initials: J
authors.lastname: Wong
authors.forename: Linda
authors.initials: L
authors.lastname: Titus-Ernstoff
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D019098:Telomerase / Q000097:blood / Q000235:genetics*; D016615:Telomere / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C509186:TERT protein, human; D019098:Telomerase