Xu Yifan, Xu Junfeng, Chancoco Haidee, Huang Maosheng, Torres Keila E, Gu Jian
Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2020 Mar 5;12(3):594. doi: 10.3390/cancers12030594.
Leukocyte telomere length (LTL) has been associated with the risks of several cancers in observational studies. Mendelian randomization (MR) studies, using genetic variants as instrumental variables, have also shown associations of genetically predicted LTL with cancer risks. In this study, we performed the first MR analysis on soft tissue sarcoma (STS) to investigate the causal relationship between LTL and the risk of STS.
Genotypes from eleven LTL-associated single nucleotide polymorphisms (SNPs) in 821 STS cases and 851 cancer-free controls were aggregated into a weighted genetic risk score (GRS) to predict LTL. Multivariate logistic regression was used to assess the association of STS risk with individual SNPs and aggregated GRS.
Four SNPs displayed evidence for an individual association between long LTL-conferring allele and increased STS risk: rs7675998 (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.02-1.43), rs9420907 (OR = 1.31, 95% CI = 1.08-1.59), rs8105767 (OR = 1.18, 95% CI = 1.02-1.37), and rs412658 (OR = 1.18, 95% CI = 1.02-1.36). Moreover, longer genetically predicted LTL, calculated as GRS, was strongly associated with an increased risk of STS (OR = 1.44, 95% CI = 1.18-1.75, < 0.001), and there was a significant dose-response association ( for trend <0.001 in tertile and quartile analyses). The association of longer LTL with higher STS risk was more evident in women than in men. In stratified analyses by major STS subtypes, longer LTL was significantly associated with higher risks of leiomyosarcoma and gastrointestinal stromal tumors.
Longer LTL is associated with increased risks of STS.
在观察性研究中，白细胞端粒长度（LTL）与多种癌症的风险相关。孟德尔随机化（MR）研究利用基因变异作为工具变量，也显示了基因预测的LTL与癌症风险之间的关联。在本研究中，我们首次对软组织肉瘤（STS）进行了MR分析，以研究LTL与STS风险之间的因果关系。
将821例STS病例和851例无癌对照中11个与LTL相关的单核苷酸多态性（SNP）的基因型汇总为加权遗传风险评分（GRS），以预测LTL。采用多变量逻辑回归评估STS风险与个体SNP及汇总GRS之间的关联。
四个SNP显示出携带长LTL等位基因与STS风险增加之间存在个体关联的证据：rs7675998（比值比（OR）=1.21，95%置信区间（CI）=1.02-1.43）、rs9420907（OR = 1.31，95% CI = 1.08-1.59）、rs8105767（OR = 1.18，95% CI = 1.02-1.37）和rs412658（OR = 1.18，95% CI = 1.02-1.36）。此外，以GRS计算的基因预测LTL越长，与STS风险增加密切相关（OR = 1.44，95% CI = 1.18-1.75，<0.001），并且存在显著的剂量反应关联（三分位数和四分位数分析中趋势的P<0.001）。LTL越长与STS风险越高的关联在女性中比在男性中更明显。在按主要STS亚型进行的分层分析中，较长的LTL与平滑肌肉瘤和胃肠道间质瘤的较高风险显著相关。
较长的LTL与STS风险增加相关。
