Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
Carcinogenesis. 2019 Jul 6;40(6):715-723. doi: 10.1093/carcin/bgz059.
Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study, based on arsenic-exposed 528 cases with basal cell carcinoma (BCC) of skin and 533 healthy controls, we investigated effect of telomere length, measured by real-time PCR, on the disease risk. We observed a statistically significant association between decreased telomere length and increased BCC risk [odds ratio (OR) = 5.92, 95% confidence interval (CI) = 3.92 to 9.01, P < 0.0001]. Due to confounder effect of arsenic exposure, in a two-sample Mendelian randomization (MR), telomere length associated single-nucleotide polymorphisms as instrument variables violated valid assumptions; however, one-sample MR adjusted for arsenic exposure indicated an increased risk of BCC with short telomeres. The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71 to 40.00, P < 0.0001), followed by those in medium exposure group and low exposure group. The combined effect of highest arsenic exposure and shortest telomeres on BCC risk (OR = 10.56, 95% CI = 5.14 to 21.70) showed a statistically significant departure from additivity (interaction contrast ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.
端粒长度本身是一种可遗传的特征，与包括癌症在内的多种疾病有关。在这项基于砷暴露的研究中，我们调查了实时 PCR 测量的端粒长度对疾病风险的影响，共纳入了 528 例基底细胞癌（BCC）患者和 533 名健康对照。我们观察到端粒长度缩短与 BCC 风险增加之间存在统计学显著关联[比值比（OR）=5.92，95%置信区间（CI）=3.92 至 9.01，P<0.0001]。由于砷暴露的混杂效应，在两样本孟德尔随机化（MR）中，作为工具变量的端粒长度相关单核苷酸多态性违反了有效假设；然而，调整了砷暴露的单样本 MR 表明，端粒较短会增加 BCC 的风险。砷暴露和端粒长度对 BCC 风险的交互作用具有统计学意义（P=0.02）。在基于砷暴露的每个三分位中，端粒较短的个体患 BCC 的风险增加，最高风险出现在暴露程度最高的组（OR=16.13，95%CI=6.71 至 40.00，P<0.0001），其次是中度暴露组和低暴露组。最高砷暴露和最短端粒长度对 BCC 风险的综合效应（OR=10.56，95%CI=5.14 至 21.70）表现出统计学上显著的偏离加性（交互对比比 6.56，P=0.03）。我们的结果表明，在存在砷暴露的情况下，端粒长度缩短使个体易患 BCC 的风险增加，而在砷暴露程度最高和端粒最短的个体中，这种效应具有协同作用。
