【佳學(xué)基因檢測(cè)】癌癥遺傳易感性：多態(tài)性在候選基因中的作用

腫瘤基因檢測(cè)哪家機(jī)構(gòu)賊好導(dǎo)讀

根據(jù)知悉《JAMA》在?2008 May 28;299(20):2423-36發(fā)表了一篇題目為《癌癥遺傳易感性：多態(tài)性在候選基因中的作用》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Linda M Dong,?John D Potter,?Emily White,?Cornelia M Ulrich,?Lon R Cardon,?Ulrike Peters等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究?jī)?nèi)容關(guān)鍵詞：

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腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果

背景：基因分型技術(shù)的持續(xù)進(jìn)步和將 DNA 收集納入觀察性研究導(dǎo)致了越來(lái)越多的遺傳關(guān)聯(lián)研究。目的：評(píng)估候選基因關(guān)聯(lián)研究對(duì)當(dāng)前對(duì)癌癥遺傳易感性的理解的總體進(jìn)展和貢獻(xiàn). 數(shù)據(jù)來(lái)源：我們系統(tǒng)地檢查了截至 2008 年 3 月發(fā)表的遺傳多態(tài)性和癌癥風(fēng)險(xiǎn)的薈萃分析和匯總分析結(jié)果。研究選擇：我們確定了 161 項(xiàng)薈萃分析和匯總分析，包括 18 個(gè)癌癥部位和 99 個(gè)基因。分析必須滿足以下標(biāo)準(zhǔn)：包括至少 500 個(gè)病例，以癌癥風(fēng)險(xiǎn)作為結(jié)果，不關(guān)注 HLA 抗原遺傳標(biāo)記，并以英文發(fā)表。數(shù)據(jù)提取：癌癥部位、基因名稱、變異、點(diǎn)估計(jì)的信息95% 置信區(qū)間 (CI)、等位基因頻率、研究和病例數(shù)、研究異質(zhì)性檢驗(yàn)和發(fā)表偏倚由 1 名研究者提取并由其他研究者進(jìn)行審查。結(jié)果：這 161 項(xiàng)分析評(píng)估了 344 種基因變異癌癥關(guān)聯(lián)和每個(gè)調(diào)查關(guān)聯(lián)平均包括 7.3 項(xiàng)研究和 3551 例（范圍，508-19 729 例）。通過(guò)在給定的先驗(yàn)概率和統(tǒng)計(jì)功效下估計(jì)假陽(yáng)性報(bào)告概率 (FPRP)，進(jìn)一步評(píng)估了 98 (28%) 個(gè)具有統(tǒng)計(jì)學(xué)意義的關(guān)聯(lián) (P 值 <.05) 的匯總優(yōu)勢(shì)比 (OR)。在 0.001 的先驗(yàn)概率水平和檢測(cè) OR 為 1.5 的統(tǒng)計(jì)功效下，13 個(gè)基因變異癌癥關(guān)聯(lián)仍然值得注意（FPRP <0.2）。假設(shè)非常低的先驗(yàn)概率為 0.000001，類似于在全基因組關(guān)聯(lián)研究中對(duì)隨機(jī)選擇的單核苷酸多態(tài)性假設(shè)的概率，并且檢測(cè) OR 為 1.5 的統(tǒng)計(jì)能力，4 個(gè)關(guān)聯(lián)被認(rèn)為是值得注意的，如 FPRP 所示值 <0.2：GSTM1 無(wú)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 無(wú)效和急性白血病 (OR ，1.20,95% CI，1.14-1.25,P = 8.6 x 10(-15))。當(dāng)用于確定統(tǒng)計(jì)功效的 OR 降至 1.2 時(shí)，4 個(gè)值得注意的關(guān)聯(lián)中有 2 個(gè)仍然如此：GSTM1 無(wú)效與膀胱癌和急性白血病。結(jié)論：在對(duì)候選基因關(guān)聯(lián)研究的回顧中，近三分之一的基因變異癌癥關(guān)聯(lián)具有統(tǒng)計(jì)學(xué)意義，其中編碼代謝酶的基因變異是賊一致和高度顯著的關(guān)聯(lián)。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)際數(shù)據(jù)庫(kù)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.