Genetics of Non-communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Eur J Pharmacol. 2020 Aug 15;881:173201. doi: 10.1016/j.ejphar.2020.173201. Epub 2020 May 19.
Caspase-8 plays is an essential enzyme in apoptosis pathway. Several investigation have been done to identify the relation between CASP8 polymorphisms and different human cancers, but, the findings are still debated. The aim of the current investigation is to assess if CASP8 rs3834129 (-652 6N insertion/deletion), rs1045485 G > C, rs3769818 G > A, rs6723097 A > C, rs3769821 T > C, rs13113 T > A, rs3769825 G > A, rs2293554 A > C, and rs10931936 C > T polymorphisms are linked to susceptibility of cancer. Our team has extracted the eligible studies up to July 4, 2019, from different sources. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between CASP8 polymorphisms and cancer susceptibility. Our results showed that the rs3834129 and rs1045485 polymorphisms meaningfully reduced the risk of cancer, while the rs3769818, rs3769821 and rs3769825 polymorphisms considerably increased cancer susceptibility. No association of rs6723097, rs13113, rs2293554 and rs10931936 polymorphisms was observed with cancer susceptibility. The CASP8 rs3834129 polymorphism reduced the risk of gastrointestinal, digestive tract, colorectal, breast and lung cancers. Furthermore, the cancer risk was decreased in Asian and Caucasian populations as well as population- and hospital-based studies due to this polymorphism. There was not any relation between this gene polymorphism and the risk of prostate and cervical cancer development. Regarding the CASP8 rs1045485 polymorphism, the reduced breast cancer risk along with the risk of cancer in Caucasians, population- and hospital-based studies were observed.
半胱天冬酶-8（Caspase-8）在细胞凋亡途径中起着至关重要的作用。已经进行了多项研究来确定 CASP8 多态性与不同人类癌症之间的关系，但研究结果仍存在争议。本研究旨在评估 CASP8 rs3834129（-652 6N 插入/缺失）、rs1045485 G>C、rs3769818 G>A、rs6723097 A>C、rs3769821 T>C、rs13113 T>A、rs3769825 G>A、rs2293554 A>C 和 rs10931936 C>T 多态性是否与癌症易感性有关。我们的团队从不同来源提取了截至 2019 年 7 月 4 日的合格研究。使用合并的优势比（OR）及其 95%置信区间（CI）来定量评估 CASP8 多态性与癌症易感性之间的关系。我们的结果表明，rs3834129 和 rs1045485 多态性显著降低了癌症的风险，而 rs3769818、rs3769821 和 rs3769825 多态性显著增加了癌症的易感性。rs6723097、rs13113、rs2293554 和 rs10931936 多态性与癌症易感性无关。CASP8 rs3834129 多态性降低了胃肠道、消化道、结直肠癌、乳腺癌和肺癌的风险。此外，由于这种多态性，亚洲人和高加索人群以及基于人群和医院的研究也降低了癌症风险。这种基因多态性与前列腺癌和宫颈癌发展的风险之间没有任何关系。关于 CASP8 rs1045485 多态性，观察到乳腺癌风险降低以及高加索人群、基于人群和医院的研究中的癌症风险降低。
