title: Long telomere length and a TERT-CLPTM1 locus polymorphism association with melanoma risk.
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.
authors.affiliation: Department of Hematology and Medical Oncology, Health Research Institute-INCLIVA, Valencia, Spain.
authors.forename: Marta J
authors.initials: MJ
authors.lastname: Llorca-Cardeñosa
authors.affiliation: Department of Hematology and Medical Oncology, Health Research Institute-INCLIVA, Valencia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Peña-Chilet
authors.affiliation: Dermatology Unit, La Paz Hospital, Madrid, Spain.
authors.forename: Matias
authors.initials: M
authors.lastname: Mayor
authors.affiliation: Dermatology Unit, La Paz Hospital, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gomez-Fernandez
authors.affiliation: Dermatology Unit, La Paz Hospital, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Casado
authors.affiliation: Dermatology Unit, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Martin-Gonzalez
authors.affiliation: Dermatology Unit, Dr. Negrin Hospital, Gran Canaria, Spain.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Carretero
authors.affiliation: Department of Hematology and Medical Oncology, Health Research Institute-INCLIVA, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.affiliation: Department of Medicine, University Jaume I of Castellon, Castellon, Spain.
authors.forename: Conrado
authors.initials: C
authors.lastname: Martinez-Cadenas
authors.affiliation: Department of Hematology and Medical Oncology, Health Research Institute-INCLIVA, Valencia, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.affiliation: Department of Hematology and Medical Oncology, Health Research Institute-INCLIVA, Valencia, Spain. Electronic address: gribasdespuig@gmail.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics; D000096142:Cutaneous Malignant Melanoma
chemical_list: C116466:CLPTM1 protein, human; D008565:Membrane Proteins; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase
keywords: Case–control study; Cutaneous melanoma; Susceptibility; TERT-CLPTM1 locus; Telomere length