title: On the interplay of telomeres, nevi and the risk of melanoma.
abstract: The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Clara
authors.initials: C
authors.lastname: Bodelon
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Julien
authors.initials: J
authors.lastname: Debbache
authors.forename: Donato
authors.initials: D
authors.lastname: Calista
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Fargnoli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarra
authors.forename: Ketty
authors.initials: K
authors.lastname: Peris
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdette
authors.forename: Laura
authors.initials: L
authors.lastname: Burke
authors.forename: Shenying
authors.initials: S
authors.lastname: Fang
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.forename: Christopher
authors.initials: C
authors.lastname: Amos
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D004416:Dysplastic Nevus Syndrome / Q000150:complications / Q000473:pathology; D004781:Environmental Exposure / Q000009:adverse effects / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D009506:Nevus / Q000150:complications* / Q000473:pathology; D010858:Pigmentation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012878:Skin Neoplasms / Q000150:complications* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects; D016615:Telomere / Q000235:genetics*; D055815:Young Adult