Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.
J Cancer Res Clin Oncol. 2023 Nov;149(16):14889-14900. doi: 10.1007/s00432-023-05193-0. Epub 2023 Aug 21.
Resistin, a novel pro-inflammatory protein implicated in inflammatory processes, has been suggested to play a role in colorectal development. However, evidence from observational studies has been inconsistent. Mendelian randomization may be a complementary method to examine this association.
We conducted a two-sample Mendelian randomization to estimate the association between genetically determined circulating resistin concentrations and risk of colorectal cancer (CRC). Protein quantitative trait loci (pQTLs) from the SCALLOP consortium were used as instrumental variables (IVs) for resistin. CRC genetic summary data was obtained from GECCO/CORECT/CCFR (the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry), and FinnGen (Finland Biobank). The inverse variance weighted method (IVW) was applied in the main analysis, and other robust methods were used as sensitivity analyses. Estimates for the association from the two data sources were then pooled using a meta-analysis approach.
Thirteen pQTLs were identified as IVs explaining together 7.80% of interindividual variation in circulating resistin concentrations. Based on MR analyses, genetically determined circulating resistin concentrations were not associated with incident CRC (pooled-IVW-OR per standard deviation of resistin, 1.01; 95% CI 0.96, 1.06; p = 0.67. Restricting the analyses to using IVs within or proximal to the resistin-encoding gene (cis-IVs), or to IVs located elsewhere in the genome (trans-IVs) provided similar results. The association was not altered when stratified by sex or CRC subsites.
We found no evidence of a relationship between genetically determined circulating resistin concentrations and risk of CRC.
抵抗素是一种新型的促炎蛋白，与炎症过程有关，被认为在结直肠发育中起作用。然而，观察性研究的证据并不一致。孟德尔随机化可能是检验这种关联的一种补充方法。
我们进行了两样本孟德尔随机化，以估计遗传决定的循环抵抗素浓度与结直肠癌（CRC）风险之间的关联。SCALLOP 联盟的蛋白质数量性状基因座（pQTL）被用作抵抗素的工具变量（IV）。CRC 遗传汇总数据来自 GECCO/CORECT/CCFR（结直肠癌遗传学和流行病学研究联盟、结直肠癌跨学科研究和结肠癌家族登记处）和 FinnGen（芬兰生物银行）。主要分析采用逆方差加权法（IVW），其他稳健方法作为敏感性分析。然后使用荟萃分析方法汇总来自两个数据源的关联估计值。
确定了 13 个 pQTL 作为 IV，共同解释了循环抵抗素浓度个体间变异的 7.80%。基于 MR 分析，遗传决定的循环抵抗素浓度与 CRC 事件无关（每标准偏差抵抗素的汇总-IVW-OR，1.01；95%CI 0.96，1.06；p=0.67）。将分析限制为使用位于抵抗素编码基因内或附近的 IV（顺式-IV）或位于基因组其他位置的 IV（反式-IV），得到了类似的结果。按性别或 CRC 亚部位分层时，关联没有改变。
我们没有发现遗传决定的循环抵抗素浓度与 CRC 风险之间存在关系的证据。
