【佳学基因检测】癌症遗传易感性：多态性在候选基因中的作用

肿瘤基因检测哪家机构最好导读

根据知悉《JAMA》在 2008 May 28;299(20):2423-36发表了一篇题目为《癌症遗传易感性：多态性在候选基因中的作用》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Linda M Dong, John D Potter, Emily White, Cornelia M Ulrich, Lon R Cardon, Ulrike Peters等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

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肿瘤靶向治疗基因检测临床应用结果

背景：基因分型技术的持续进步和将 DNA 收集纳入观察性研究导致了越来越多的遗传关联研究。目的：评估候选基因关联研究对当前对癌症遗传易感性的理解的总体进展和贡献. 数据来源：我们系统地检查了截至 2008 年 3 月发表的遗传多态性和癌症风险的荟萃分析和汇总分析结果。研究选择：我们确定了 161 项荟萃分析和汇总分析，包括 18 个癌症部位和 99 个基因。分析必须满足以下标准：包括至少 500 个病例，以癌症风险作为结果，不关注 HLA 抗原遗传标记，并以英文发表。数据提取：癌症部位、基因名称、变异、点估计的信息95% 置信区间 (CI)、等位基因频率、研究和病例数、研究异质性检验和发表偏倚由 1 名研究者提取并由其他研究者进行审查。结果：这 161 项分析评估了 344 种基因变异癌症关联和每个调查关联平均包括 7.3 项研究和 3551 例（范围，508-19 729 例）。通过在给定的先验概率和统计功效下估计假阳性报告概率 (FPRP)，进一步评估了 98 (28%) 个具有统计学意义的关联 (P 值 <.05) 的汇总优势比 (OR)。在 0.001 的先验概率水平和检测 OR 为 1.5 的统计功效下，13 个基因变异癌症关联仍然值得注意（FPRP <0.2）。假设非常低的先验概率为 0.000001，类似于在全基因组关联研究中对随机选择的单核苷酸多态性假设的概率，并且检测 OR 为 1.5 的统计能力，4 个关联被认为是值得注意的，如 FPRP 所示值 <0.2：GSTM1 无效和膀胱癌（OR，1.5,95% CI，1.3-1.6,P = 1.9 x 10(-14)），NAT2 慢乙酰化和膀胱癌（OR，1.46,95% CI，1.26- 1.68,P = 2.5 x 10(-7))，MTHFR C677T 和胃癌 (OR, 1.52; 95% CI, 1.31-1.77; P = 4.9 x 10(-8))，以及 GSTM1 无效和急性白血病 (OR ，1.20,95% CI，1.14-1.25,P = 8.6 x 10(-15))。当用于确定统计功效的 OR 降至 1.2 时，4 个值得注意的关联中有 2 个仍然如此：GSTM1 无效与膀胱癌和急性白血病。结论：在对候选基因关联研究的回顾中，近三分之一的基因变异癌症关联具有统计学意义，其中编码代谢酶的基因变异是最一致和高度显着的关联。

肿瘤发生与复发转移国际数据库描述：

Context: Continuing advances in genotyping technologies and the inclusion of DNA collection in observational studies have resulted in an increasing number of genetic association studies.Objective: To evaluate the overall progress and contribution of candidate gene association studies to current understanding of the genetic susceptibility to cancer.Data sources: We systematically examined the results of meta-analyses and pooled analyses for genetic polymorphisms and cancer risk published through March 2008.Study selection: We identified 161 meta-analyses and pooled analyses, encompassing 18 cancer sites and 99 genes. Analyses had to meet the following criteria: include at least 500 cases, have cancer risk as outcome, not be focused on HLA antigen genetic markers, and be published in English.Data extraction: Information on cancer site, gene name, variant, point estimate and 95% confidence interval (CI), allelic frequency, number of studies and cases, tests of study heterogeneity, and publication bias were extracted by 1 investigator and reviewed by other investigators.Results: These 161 analyses evaluated 344 gene-variant cancer associations and included on average 7.3 studies and 3551 cases (range, 508-19 729 cases) per investigated association. The summary odds ratio (OR) for 98 (28%) statistically significant associations (P value <.05) were further evaluated by estimating the false-positive report probability (FPRP) at a given prior probability and statistical power. At a prior probability level of 0.001 and statistical power to detect an OR of 1.5, 13 gene-variant cancer associations remained noteworthy (FPRP <0.2). Assuming a very low prior probability of 0.000001, similar to a probability assumed for a randomly selected single-nucleotide polymorphism in a genome-wide association study, and statistical power to detect an OR of 1.5, 4 associations were considered noteworthy as denoted by an FPRP value <0.2: GSTM1 null and bladder cancer (OR, 1.5; 95% CI, 1.3-1.6; P = 1.9 x 10(-14)), NAT2 slow acetylator and bladder cancer (OR, 1.46; 95% CI, 1.26-1.68; P = 2.5 x 10(-7)), MTHFR C677T and gastric cancer (OR, 1.52; 95% CI, 1.31-1.77; P = 4.9 x 10(-8)), and GSTM1 null and acute leukemia (OR, 1.20; 95% CI, 1.14-1.25; P = 8.6 x 10(-15)). When the OR used to determine statistical power was lowered to 1.2, 2 of the 4 noteworthy associations remained so: GSTM1 null with bladder cancer and acute leukemia.Conclusion: In this review of candidate gene association studies, nearly one-third of gene-variant cancer associations were statistically significant, with variants in genes encoding for metabolizing enzymes among the most consistent and highly significant associations.