Zhang Zhizhong, Qiu Lixin, Wang Meilin, Tong Na, Li Jin, Zhang Zhengdong
Department of Molecular and Genetic Toxicology, Cancer Center of Nanjing Medical University, Nanjing, China.
Eur J Hum Genet. 2009 Oct;17(10):1294-303. doi: 10.1038/ejhg.2009.45. Epub 2009 Apr 1.
The potentially functional polymorphism, rs763110 (-844C>T), in the promoter region of the FAS ligand (FASL) gene, has been implicated in cancer risk, but individually published studies show inconclusive results. To derive a more precise estimation of the association between the FASL rs763110 and risk of cancer, we performed a meta-analysis of 19 published studies that included 11,105 cancer cases and 11,372 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Overall, the rs763110 CT and TT variant genotypes were associated with a significantly reduced cancer risk of all cancer types in different genetic models (homozygote comparison: OR=0.80, 95% CI: 0.68-0.95, P(heterogeneity)=0.001; heterozygote comparison: OR=0.82, 95% CI: 0.72-0.95, P(heterogeneity)<0.001; dominant model comparison: OR=0.82, 95% CI: 0.71-0.94, P(heterogeneity)<0.001; and recessive model comparison: OR=0.88, 95% CI: 0.81-0.96, P(heterogeneity)=0.074). In the stratified analyses, the risk remained for studies of the smoking-related cancers and Asian populations, or population-based studies in all the genetic models. Although some modest bias could not be eliminated, this meta-analysis suggests that the FASL rs763110 T allele has a possible protective effect on cancer risk.
FAS配体(FASL)基因启动子区域中具有潜在功能的多态性rs763110(-844C>T)与癌症风险有关,但个别已发表的研究结果尚无定论。为了更精确地估计FASL rs763110与癌症风险之间的关联,我们对19项已发表的研究进行了荟萃分析,这些研究包括11105例癌症病例和11372例对照。我们使用优势比(OR)和95%置信区间(CI)来评估关联强度。总体而言,在不同遗传模型中,rs763110的CT和TT变异基因型与所有癌症类型的癌症风险显著降低相关(纯合子比较:OR=0.80,95%CI:0.68-0.95,P(异质性)=0.001;杂合子比较:OR=0.82,95%CI:0.72-0.95,P(异质性)<0.001;显性模型比较:OR=0.82,95%CI:0.71-0.94,P(异质性)<0.001;隐性模型比较:OR=0.88,95%CI:0.81-0.96,P(异质性)=0.074)。在分层分析中,吸烟相关癌症和亚洲人群的研究或所有遗传模型中的基于人群的研究中,风险依然存在。尽管一些适度的偏倚无法消除,但这项荟萃分析表明FASL rs763110的T等位基因可能对癌症风险具有保护作用。