Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families With and Without CDKN2A Mutations

PLoS One. 2013 Aug 19;8(8):e71121. doi: 10.1371/journal.pone.0071121. eCollection 2013.

Abstract

Introduction: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations.

Materials and methods: We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT.

Results: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02-7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction.

Discussion: Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Germ-Line Mutation
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Middle Aged
  • Mutation*
  • Phenotype
  • Pigmentation
  • Polymorphism, Single Nucleotide
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Sunlight
  • Telomere / ultrastructure

Substances

  • Cyclin-Dependent Kinase Inhibitor p16

Supplementary concepts

  • Melanoma, Cutaneous Malignant

Grant support

Paula Hyland was funded by the Cancer Prevention Fellowship Program, the Center for Cancer Training, National Cancer Institute, Bethesda, United States of America and the Health and Social Care, Northern Ireland, United Kingdom. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.