Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.
Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.
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DOI：
10.1186/s12916-021-02193-0
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发表时间：
2022-01-11
期刊：
影响因子：
9.3
通讯作者：
Tsilidis KK
中科院分区：
文献类型：
--
作者：
Bouras E;Karhunen V;Gill D;Huang J;Haycock PC;Gunter MJ;Johansson M;Brennan P;Key T;Lewis SJ;Martin RM;Murphy N;Platz EA;Travis R;Yarmolinsky J;Zuber V;Martin P;Katsoulis M;Freisling H;Nøst TH;Schulze MB;Dossus L;Hung RJ;Amos CI;Ahola-Olli A;Palaniswamy S;Männikkö M;Auvinen J;Herzig KH;Keinänen-Kiukaanniemi S;Lehtimäki T;Salomaa V;Raitakari O;Salmi M;Jalkanen S;PRACTICAL consortium;Jarvelin MR;Dehghan A;Tsilidis KK
流行病学和实验证据已经将慢性炎症与癌症病因联系起来。目前尚不清楚特定炎症生物标志物的相关性是因果关系还是由于偏倚。为了检查循环细胞因子的遗传预测浓度是否与癌症发展相关，我们进行了双样本孟德尔随机化（MR）分析。多达31，112名欧洲血统的个体被纳入47种循环细胞因子的全基因组关联研究（GWAS）荟萃分析。单核苷酸多态性（SNPs）与细胞因子，位于或接近其编码基因（顺式），被用作工具变量。使用逆方差加权MR作为主要分析，在敏感性和共定位分析中评价MR假设，并对多重比较应用错误发现率（FDR）校正。五种癌症（乳腺癌、子宫内膜癌、肺癌、卵巢癌和前列腺癌）及其亚型的相应生殖系GWAS总结数据选自现有最大的癌症特异性GWAS（病例范围从子宫内膜癌的12，906例到乳腺癌的133，384例）。有证据表明巨噬细胞移动抑制因子与乳腺癌呈负相关（OR/SD = 0.88，95% CI 0.83 - 0.94），白细胞介素-1受体拮抗剂与子宫内膜癌（0.86，0.80 ~ 0.93），白细胞介素18与肺癌（0.87，0.81至0.93），和β-趋化因子-RANTES与卵巢癌（0.70，0.57 ~ 0.85）及γ-干扰素诱导的单核细胞因子与子宫内膜癌的正相关性（3.73，1.86 ~ 7.47）和皮肤T细胞趋化因子与肺癌的关系（1.51，1.22 ~ 1.87）。这些关联在敏感性分析中是相似的，并在共定位分析中得到支持。我们的研究增加了目前关于特定炎症生物标志物途径在癌症病因学中的作用的知识。需要进一步验证，以评估这些细胞因子作为预防癌症的药理学或生活方式靶点的潜力。在线版本包含补充材料，可通过10.1186/s12916-021-02193-0获得。
Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention. The online version contains supplementary material available at 10.1186/s12916-021-02193-0.
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影响因子：
14.9
作者：
Davies M;Nowotka M;Papadatos G;Dedman N;Gaulton A;Atkinson F;Bellis L;Overington JP
通讯作者：
Overington JP
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
6
作者：
Ignacio RMC;Lee ES;Wilson AJ;Beeghly-Fadiel A;Whalen MM;Son DS
通讯作者：
Son DS
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y