Rode Line, Nordestgaard Børge G, Bojesen Stig E
Department of Clinical Biochemistry and Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry and Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Int J Epidemiol. 2016 Oct;45(5):1634-1643. doi: 10.1093/ije/dyw179. Epub 2016 Aug 6.
Results regarding telomere length and cancer risk are conflicting. We tested the hypothesis that long telomeres are associated with increased risk of any cancer and specific cancer types in genetic and observational analyses.
Individuals (N = 95 568) from the Copenhagen City Heart Study and the Copenhagen General Population Study had the telomere length-associated genotypes rs7726159 (TERT), rs1317082 (TERC), and rs2487999 (OBFC1) determined, and 65 176 had telomere length measured. A total of 10 895 individuals had had a cancer diagnosis. Endpoints were any cancer and 25 specific cancer types. We conducted Cox regression analyses and logistic regression analyses. The three genotypes were combined as an allele sum.
Telomere length increased 67 base-pairs [95% confidence interval (CI) 61-74] per allele. In logistic regression models, the per-allele odds ratio (OR) for cancer was 1.05 (95% CI 1.03-1.07) for the allele sum, 1.05 (1.02-1.09) for rs7726159, 1.05 (1.02-1.08) for rs1317082 and 1.07 (1.02-1.12) for rs2487999. In contrast, the hazard ratio for any cancer was 1.01 (1.00-1.01) per 200-base-pair increase in telomere length in multivariable adjusted observational analysis. In genetic analyses according to specific cancer types, the per-allele odds ratio was 1.19 (1.12-1.27) for melanoma and 1.14 (1.06-1.22) for lung cancer.
Genetic determinants of long telomeres are associated with increased cancer risk, particularly melanoma and lung cancer. This genetic predisposition to enhanced telomere maintenance may represent a survival advantage for pre-cancerous cells, allowing for multiple cell divisions leading to cancer development.
关于端粒长度与癌症风险的研究结果相互矛盾。我们在基因分析和观察性分析中检验了长端粒与任何癌症及特定癌症类型风险增加相关的假设。
哥本哈根城市心脏研究和哥本哈根普通人群研究中的个体（N = 95568）测定了与端粒长度相关的基因型rs7726159（TERT）、rs1317082（TERC）和rs2487999（OBFC1），65176人测量了端粒长度。共有10895人被诊断患有癌症。终点指标为任何癌症和25种特定癌症类型。我们进行了Cox回归分析和逻辑回归分析。将这三种基因型合并为等位基因总和。
每个等位基因端粒长度增加67个碱基对[95%置信区间（CI）61 - 74]。在逻辑回归模型中，等位基因总和每增加一个等位基因患癌的比值比（OR）为1.05（95%CI 1.03 - 1.07），rs7726159为1.05（1.02 - 1.09），rs1317082为1.05（1.02 - 1.08），rs2487999为1.07（1.02 - 1.12）。相比之下，在多变量调整的观察性分析中，端粒长度每增加200个碱基对，任何癌症的风险比为1.01（1.00 - 1.01）。在根据特定癌症类型进行的基因分析中，黑色素瘤每个等位基因的比值比为1.19（1.12 - 1.27），肺癌为1.14（1.06 - 1.22）。
长端粒的基因决定因素与癌症风险增加相关，尤其是黑色素瘤和肺癌。这种增强端粒维持的遗传易感性可能代表癌前细胞的生存优势，允许进行多次细胞分裂从而导致癌症发展。
