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8q24区域多个变异与癌症发病率之间关系的累积证据。

Cumulative evidence of relationships between multiple variants in 8q24 region and cancer incidence.

作者信息

Tong Yu, Tang Ying, Li Shiping, Zhao Fengyan, Ying Junjie, Qu Yi, Niu Xiaoyu, Mu Dezhi

机构信息

Department of Pediatrics.

Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education.

出版信息

Medicine (Baltimore). 2020 Jun 26;99(26):e20716. doi: 10.1097/MD.0000000000020716.

Abstract

Genome-wide association studies (GWAS) have identified multiple independent cancer susceptibility loci at chromosome 8q24. We aimed to evaluate the associations between variants in the 8q24 region and cancer susceptibility. A comprehensive research synopsis and meta-analysis was performed to evaluate associations between 28 variants in 8q24 and risk of 7 cancers using data from 103 eligible articles totaling 146,932 cancer cases and 219,724 controls. Results: 20 variants were significantly associated with risk of prostate cancer, colorectal cancer, thyroid cancer, breast cancer, bladder cancer, stomach cancer, and glioma, including 1 variant associated with prostate cancer, colorectal cancer, and thyroid cancer. Cumulative epidemiological evidence of an association was graded as strong for DG8S737 -8 allele, rs10090154, rs7000448 in prostate cancer, rs10808556 in colorectal cancer, rs55705857 in gliomas, rs9642880 in bladder cancer, moderate for rs16901979, rs1447295, rs6983267, rs7017300, rs7837688, rs1016343, rs620861, rs10086908 associated in prostate cancer, rs10505477, rs6983267 in colorectal cancer, rs6983267 in thyroid cancer, rs13281615 in breast cancer, and rs1447295 in stomach cancer, weak for rs6983561, rs13254738, rs7008482, rs4242384 in prostate cancer. Data from ENCODE suggested that these variants with strong evidence and other correlated variants might fall within putative functional regions. Our study provides summary evidence that common variants in the 8q24 are associated with risk of multiple cancers in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the mechanisms underlying variants in the 8q24 involved in various human cancers.

摘要

全基因组关联研究(GWAS)已在8号染色体q24区域确定了多个独立的癌症易感基因座。我们旨在评估8q24区域变异与癌症易感性之间的关联。利用来自103篇符合条件的文章的数据(共146,932例癌症病例和219,724例对照),进行了一项全面的研究综述和荟萃分析,以评估8q24区域的28个变异与7种癌症风险之间的关联。结果:20个变异与前列腺癌、结直肠癌、甲状腺癌、乳腺癌、膀胱癌、胃癌和神经胶质瘤的风险显著相关,其中1个变异与前列腺癌、结直肠癌和甲状腺癌相关。对于前列腺癌中的DG8S737 -8等位基因、rs10090154、rs7000448,结直肠癌中的rs10808556,神经胶质瘤中的rs55705857,膀胱癌中的rs9642880,关联的累积流行病学证据被评为强;对于前列腺癌中关联的rs16901979、rs1447295、rs6983267、rs7017300、rs7837688、rs1016343、rs620861、rs10086908,结直肠癌中的rs10505477、rs6983267,甲状腺癌中的rs6983267,乳腺癌中的rs13281615,胃癌中的rs1447295,关联的累积流行病学证据被评为中等;对于前列腺癌中的rs6983561、rs13254738、rs7008482、rs4242384,关联的累积流行病学证据被评为弱。来自ENCODE的数据表明,这些有充分证据的变异以及其他相关变异可能位于假定的功能区域内。在这项大规模研究综述和荟萃分析中,我们的研究提供了总结性证据,表明8q24中的常见变异与多种癌症的风险相关。需要进一步研究来探索8q24中涉及各种人类癌症的变异的潜在机制。

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