Long telomere length and a TERT-CLPTM1 locus polymorphism association with melanoma risk

Eur J Cancer. 2014 Dec;50(18):3168-77. doi: 10.1016/j.ejca.2014.09.017. Epub 2014 Oct 31.

Abstract

Telomere length has been associated with the development of cancer. Studies have shown that shorter telomere length may be related to a decreased risk of cutaneous melanoma. Furthermore, deregulation of the telomere-maintaining gene complexes, has been related to this oncogenic process. Some variants in these genes seem to be correlated with a change in telomerase expression. We examined the effect of 10 single nucleotide polymorphisms (SNPs) in the TERT gene (encoding telomerase), one SNP in the related TERT-CLPTM1L locus and one SNP in the TRF1 gene with telomere length, and its influence on melanoma risk in 970 Spanish cases and 733 Spanish controls. Genotypes were determined using KASP technology, and telomere length was measured by quantitative polymerase chain reaction (PCR) on DNA extracted from peripheral blood leucocytes. Our results demonstrate that shorter telomere length is associated with a decreased risk of melanoma in our population (global p-value, 2.69×10(-11)), which may be caused by a diminution of proliferative potential of nevi (melanoma precursor cells). We also obtained significant results when we tested the association between rs401681 variant (TERT-CLPTM1L locus) with melanoma risk (Odds ratio, OR; 95% confidence interval, CI=1.24 (1.08-1.43); p-value, 3×10(-3)). This is the largest telomere-related study undertaken in a Spanish population to date. Furthermore, this study represents a comprehensive analysis of some of the most relevant telomere pathway genes in relation to cutaneous melanoma susceptibility.

Keywords: Case–control study; Cutaneous melanoma; Susceptibility; TERT-CLPTM1 locus; Telomere length.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma, Cutaneous Malignant
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Skin Neoplasms / genetics*
  • Telomerase / genetics*
  • Telomere / genetics*
  • Telomeric Repeat Binding Protein 1 / genetics

Substances

  • CLPTM1 protein, human
  • Membrane Proteins
  • Telomeric Repeat Binding Protein 1
  • Telomerase