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Shorter telomere length is associated with increased ovarian cancer risk in both familial and sporadic cases
  1. Beatriz Martinez-Delgado1,2,
  2. Kira Yanowsky1,2,
  3. Lucia Inglada-Perez2,3,
  4. Miguel de la Hoya4,
  5. Trinidad Caldes4,
  6. Ana Vega2,5,
  7. Ana Blanco2,5,
  8. Teresa Martin6,
  9. Rogelio Gonzalez-Sarmiento7,
  10. Maria Blasco8,
  11. Mercedes Robledo2,3,
  12. Miguel Urioste1,2,
  13. Honglin Song9,
  14. Paul Pharoah9,10,
  15. Javier Benitez1,2
  1. 1Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  2. 2Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
  3. 3Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  4. 4Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain
  5. 5Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, IDIS, Santiago de Compostela, Spain
  6. 6Servicio de Oncología, Hospital Universitario de Salamanca, Salamanca, Spain
  7. 7IBMCC, Universidad de Salamanca-CSIC, Salamanca, Spain
  8. 8Telomeres and Telomerase Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
  9. 9Department of Oncology, University of Cambridge, Cambridge, UK
  10. 10Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  1. Correspondence to Dr Beatriz Martinez-Delgado, Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, Madrid 28029, Spain; bmartinez{at}cnio.es

Abstract

Background Alterations in telomere maintenance mechanisms leading to short telomeres underlie different genetic disorders of ageing and cancer predisposition syndromes. It is known that short telomeres and subsequent genomic instability contribute to malignant transformation, and it is therefore likely that people with shorter telomeres are at higher risk for different types of cancer. Recently, the authors demonstrated that the genes BRCA1 and BRCA2 are modifiers of telomere length (TL) in familial breast cancer. The present study analysed TL in peripheral blood leucocytes of hereditary and sporadic ovarian cancer cases, as well as in female controls, to evaluate whether TL contributes to ovarian cancer risk.

Methods TL was measured by quantitative PCR in 178 sporadic and 168 hereditary ovarian cases (46 BRCA1, 12 BRCA2, and 110 BRCAX) and compared to TL in 267 controls.

Results Both sporadic and hereditary cases showed significantly shorter age adjusted TLs than controls. Unconditional logistic regression analysis revealed an association between TL and ovarian cancer risk with a significant interaction with age (p<0.001). Risk was higher in younger women and progressively decreased with age, with the highest OR observed in women under 30 years of age (OR 1.56, 95% CI 1.34 to 1.81; p=1.0×10−18).

Conclusion These findings indicate that TL could be a risk factor for early onset ovarian cancer.

  • Ovarian cancer
  • BRCA1 and BRCA2 genes
  • Telomeres
  • risk factors
  • case-control study
  • cancer: breast
  • genome-wide
  • genetics
  • microarray
  • microRNA
  • genetic epidemiology
  • thyroid disease
  • clinical genetics
  • diagnostics
  • genetic screening/counselling
  • dermatology
  • cancer: endocrine
  • oncology
  • molecular genetics
  • cancer: head and neck

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Footnotes

  • Funding This work was supported by Genetic Counseling Programme in Hereditary Cancer (Junta de Castilla y León) grant number FIS PI10/00219 (RGS); the Spanish Association Against Cancer (AECC), FIS PI08-1120 and by Red Tematica de investigacion Cooperativa en Cancer grant number RETICC RD06/0020/1060 (JB), and RETICC 06/0020/0021 (TC and MH); by the Xunta de Galicia grant number 10PXIB 9101297PR and Fundación Mutua Madrileña (AV).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The ethics approval was provided by the ethics committee of the Instituto de Salud Carlos III, Spain.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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