Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, United States of America.
PLoS One. 2013 Aug 19;8(8):e71121. doi: 10.1371/journal.pone.0071121. eCollection 2013.
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.
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.
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.
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.
最近的证据表明，端粒长度与癌症风险之间存在关联。先前的研究表明，端粒较长与黑色素瘤风险增加以及痣的大小和数量增加有关。本研究的目的是检查在有和没有 CDKN2A 种系突变的易患黑色素瘤家族中，TL 是否改变了黑色素瘤的风险。
我们测量了 119 例皮肤恶性黑色素瘤（CMM）病例和 208 例无病个体血液 DNA 中的 TL。我们还对 TERT 中的 13 个标记 SNP 进行了基因分型。
我们发现较长的端粒与 CMM 风险增加相关（调整后的 OR = 2.81，95% CI = 1.02-7.72，P = 0.04）。较长 TL 与 CMM 风险的关联仅见于 CDKN2A-病例，而不见于 CDKN2A+病例。在 CMM 病例中，存在日光损伤与较短的端粒相关（P = 0.002）。TERT 中的一个 SNP，rs2735940，在经过 Bonferroni 校正后与 TL 显著相关（P = 0.002）。
我们的发现表明，TL 调节可能因 CDKN2A 突变状态、日晒和色素沉着表型而异。因此，TL 测量本身可能不是预测 CMM 风险的良好标志物。
