Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, 2 Worts Causeway, Cambridge CB18RN, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1862-5. doi: 10.1158/1055-9965.EPI-10-0281. Epub 2010 Jun 22.
A recent study reported genetic variants in the TERT-CLPTM1L locus that were associated with mean telomere length, and with risk of multiple cancers.
We evaluated the association between single nucleotide polymorphism (SNP) rs401681 (C > T) and mean telomere length, using quantitative real-time PCR, in blood-extracted DNA collected from 11,314 cancer-free participants from the Sisters in Breast Screening study, the Melanoma and Pigmented Lesions Evaluative Study melanoma family study, and the SEARCH Breast, Colorectal, Melanoma studies. We also examined the relationship between rs401618 genotype and susceptibility to breast cancer (6,800 cases and 6,608 controls), colorectal cancer (2,259 cases and 2,181 controls), and melanoma (787 cases and 999 controls).
The "per T allele" change in mean telomere length (DeltaCt), adjusted for age, study plate, gender, and family was 0.001 [95% confidence intervals (CI), 0.01-0.02; P trend = 0.61]. The "per T allele" odds ratio for each cancer was 1.01 for breast cancer (95% CI, 0.96-1.06; P trend = 0.64), 1.02 for colorectal cancer (95% CI, 0.94-1.11; P trend = 0.66), and 0.99 for melanoma (95% CI, 0.84-1.15; P trend = 0.87).
We found no evidence that this SNP was associated with mean telomere length, or with risk of breast cancer, colorectal cancer, or melanoma.
Our results indicate that the observed associations between rs401681 and several cancer types might be weaker than previously described. The lack of an association in our study between this SNP and mean telomere length suggests that any association with cancer risk at this locus is not mediated through TERT.
最近的一项研究报告称，TERT-CLPTM1L 基因座的遗传变异与端粒平均长度相关，也与多种癌症的风险相关。
我们评估了单核苷酸多态性（SNP）rs401681（C>T）与定量实时 PCR 检测到的血液提取 DNA 中端粒平均长度之间的关联，该 SNP 来自于无癌症的 11314 名姐妹乳腺癌筛查研究、黑色素瘤和色素斑评价研究黑色素瘤家系研究，以及 SEARCH 乳腺、结直肠、黑色素瘤研究的参与者。我们还检查了 rs401618 基因型与乳腺癌（6800 例病例和 6608 例对照）、结直肠癌（2259 例病例和 2181 例对照）和黑色素瘤（787 例病例和 999 例对照）易感性之间的关系。
校正年龄、研究板、性别和家族后，端粒平均长度的 T 等位基因变化（DeltaCt）为 0.001[95%置信区间（CI），0.01-0.02；P 趋势=0.61]。每个癌症的 T 等位基因比值比为 1.01（95%CI，0.96-1.06；P 趋势=0.64）用于乳腺癌，1.02（95%CI，0.94-1.11；P 趋势=0.66）用于结直肠癌，0.99（95%CI，0.84-1.15；P 趋势=0.87）用于黑色素瘤。
我们没有发现该 SNP 与端粒平均长度或乳腺癌、结直肠癌或黑色素瘤风险相关的证据。
我们的研究结果表明，rs401681 与几种癌症类型之间的观察到的关联可能比以前描述的更弱。在我们的研究中，该 SNP 与端粒平均长度之间缺乏关联表明，该基因座与癌症风险的任何关联都不是通过 TERT 介导的。
