Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families with and without CDKN2A Mutations

Abstract

IntroductionRecent 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 MethodsWe measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT.ResultsWe 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.DiscussionOur 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.

Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study

“…12), recent and repeated observations by different epidemiologic studies have indicated longer LTL among individuals developing cancer (12,13,(38)(39)(40)(41)(42)(43)(44). Our present data seem to be in line with this latter hypothesis; however, they do not support LTL as a uniform and strong predictor of pancreas cancer risk.…”

“…Comparison of geometric mean LTL values at different levels of baseline variables or prospective (the blood was taken before diagnosis, in a cohort study), with the retrospective studies generally showing stronger associations than the prospective studies (12). It is worth emphasizing that in several recent publications, which include prospective studies, longer telomeres were found to be associated with an increase in cancer risk (12,13,(38)(39)(40)(41)(42)(43)(44)(45). For pancreatic cancer, only two studies on the relationship with LTL have been performed so far: one retrospective case-control study, which showed an inverse association between shorter LTL and pancreas cancer risk (14), and one prospective study that showed an association between longer LTL and increased pancreatic cancer risk (13).…”

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

“…It was proposed that shorter telomere length in nevi limits proliferation and promotes senescence, protecting against malignant transformation [41,86]. At variance with the aforementioned reports, Burke and colleagues suggested that telomere length can also be influenced by CDKN2A mutational status (a high-risk melanoma susceptibility gene), sun exposure and pigmentation phenotype and therefore cannot be considered a biomarker to predict melanoma risk per se [12]. Two seminal papers reported high frequency of TERT promoter mutations in familial and sporadic melanoma [50,53].…”

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

“…Furthermore, it has been shown that telomere length may be related with cancer risk and with genetic variants in genes encoding telomerase protein complex components, respectively [12][13][14][15][16][17][18][19][20].…”