Longer telomeres are associated with cancer risk in MMR-proficient hereditary non-polyposis colorectal cancer

PLoS One. 2014 Feb 3;9(2):e86063. doi: 10.1371/journal.pone.0086063. eCollection 2014.

Abstract

Aberrant telomere length measured in blood has been associated with increased risk of several cancer types. In the field of hereditary non-polyposis colorectal cancer (CRC), and more particularly in Lynch syndrome, caused by germline mutations in the mismatch repair (MMR) genes, we recently found that cancer-affected MMR gene mutation carriers had shorter telomeres and more pronounced shortening of telomere length with age than controls and unaffected MMR gene mutation carriers. Here we evaluate blood telomere length in MMR-proficient hereditary non-polyposis CRC, i.e. familial CRC type X (fCRC-X). A total of 57 cancer-affected and 57 cancer-free individuals from 34 Amsterdam-positive fCRC-X families were analyzed and compared to the data previously published on 144 cancer-affected and 100 cancer-free MMR gene mutation carriers, and 234 controls. Relative telomere length was measured using a monochrome multiplex quantitative PCR method, following strict measures to avoid sources of bias and adjusting by age. Despite the retrospective nature of our study, the results show that longer telomeres associate with cancer risk in fCRC-X, thus identifying different patterns of telomere length according to the status of the MMR system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colorectal Neoplasms, Hereditary Nonpolyposis / blood
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair / genetics*
  • Family Health
  • Female
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction / methods
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Telomere / genetics*
  • Telomere Homeostasis
  • Telomere Shortening

Grant support

This work has been funded by the Spanish Ministry of Economy (State Secretariat for Research, Development and Innovation) (grants SAF2012-38885 to LV and SAF2012-33636 to GC; and Ramón y Cajal contract to LV); L’Oréal-UNESCO “For Women in Science”; the Scientific Foundation Asociación Española Contra el Cáncer; the Catalan Government (grant 2009SGR290); and Carlos III Health Institute (fellowship to NS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.