據(jù)3月26日《美國醫(yī)學(xué)協(xié)會期刊》（JAMA）上的一則研究顯示,，那些攜帶某種特定類型純合性（即具有2種完全相同拷貝的同一基因,，它們分別遺傳自父母親）的人可能具有更大的罹患癌癥的可能性。
在過去的研究中，文章的作者觀察到生殖系（某個體的那些可以將其遺傳物質(zhì)傳遞給后代的細胞）雜合性（具有兩個不同形式的某特定基因，它們分別來自父母親）在癌癥病人中與對照組相比，其發(fā)生率很低,。這向人們提出了這樣一個問題，即純合性是否在癌癥的易感性方面扮演著某種角色,。
美國克里夫蘭臨床基金會的Charis Eng及其同事開展了一項研究,，旨在確定一個攜帶三種不同類型實質(zhì)腫瘤的大型病患人群中的生殖系雜合性的發(fā)生頻率，并與以人群為基礎(chǔ)的對照組的發(fā)生頻率進行比較,。這一研究包括將生殖系DNA及相應(yīng)的腫瘤DNA進行基因分析,，而腫瘤DNA是從385名罹患癌癥的病人（147名乳腺癌病人、116名前列腺癌病人及122名頭頸部癌癥病人）體內(nèi)分離出來的,。
研究人員表示,，“我們的數(shù)據(jù)來自三種（并在第四種腫瘤中同樣得到證實）不同的實質(zhì)腫瘤。與對照組相比,，這些數(shù)據(jù)證明在某些特別遺傳標(biāo)記處的生殖系的純合性與這些癌癥具有相關(guān)性…重要的是,，我們在一種不同類型的實質(zhì)腫瘤（即肺癌）中獨立地驗證了我們的觀測結(jié)果,，即在與祖先匹配的對照人群比較時發(fā)現(xiàn)，癌癥病例的生殖系純合性的頻率有所增加,。”
文章的作者寫道：“我們在這里所觀測到的結(jié)果應(yīng)該在這些實質(zhì)性的腫瘤中進行驗證,，并且應(yīng)該在其它類型惡性腫瘤中進行探索。如果我們的數(shù)據(jù)能夠被充分獨立地復(fù)制的話,，那么除了高外顯率癌癥易感性基因之外,，在未來的癌癥風(fēng)險評估及處理中，應(yīng)考慮生殖系雜合性以低外顯率等位基因方式存在于某些特定位點會增加罹患癌癥的可能性,。另外,，如果我們知道在那些相同位點的生殖系純合性/雜合性的相對發(fā)生頻率的話，通過進一步的研究及精細的結(jié)構(gòu)分析,，我們有可能利用這些數(shù)據(jù)來預(yù)測在某一腫瘤的特定基因位點失去雜合性的可能性,。”（來源：EurekAlert!中文版）
生物谷推薦原始出處：
（JAMA），299(12):1437-1445,，Guillaume Assié,，Charis Eng
Frequency of Germline Genomic Homozygosity Associated With Cancer Cases
Guillaume Assié, MD, PhD; Thomas LaFramboise, PhD; Petra Platzer, PhD; Charis Eng, MD, PhD
JAMA. 2008;299(12):1437-1445.
Context Cancer is a multigenic disease resulting from both germline susceptibility and somatic events. While studying loss of heterozygosity (LOH) in cancer tissues, we anecdotally observed a low frequency of heterozygosity in cancer patients compared with controls, raising the question whether homozygosity could play a role in cancer predisposition.
Objectives To determine the frequency of germline homozygosity in a large series of patients with 3 different types of solid tumors compared with population-based controls.
Design, Setting, and Patients Germline and corresponding tumor DNA isolated from 385 patients with carcinomas (147 breast, 116 prostate, and 122 head and neck carcinomas) were subjected to whole genome (345-microsatellite marker) LOH analysis.
Main Outcome Measures Frequency of homozygosity at microsatellite markers in cancer cases vs controls and frequency of somatic LOH in cancers at loci with the highest homozygosity.
Results We identified 16 loci in common among the 3 cancer types, with significantly increased germline homozygosity frequencies in the cancer patients compared with controls (P < .001). In the cases who happened to be germline heterozygous at these 16 loci, we found a mean (SD) LOH frequency of 58% (4.2%) compared with 50% (7.5%) at 197 markers without increased germline homozygosity (P < .001). Across the genome, this relationship holds as well (r = 0.46; 95% confidence interval, 0.37-0.53; P < .001). We validated the association of specific loci with high germline homozygosity frequencies in an independent, single-nucleotide polymorphism–based, public data set of 205 lung carcinomas from white individuals (P < .05 to P < .001) as well as the correlation between genome-wide germline homozygosity and LOH frequencies (r = 0.21; 95% confidence interval, 0.18-0.24; P < .001).
Conclusions In our study of 4 different types of solid tumors (our data for 3 types validated in a fourth type), increased germline homozygosity occurred at specific loci. When the germline was heterozygous at these loci, high frequencies of LOH/allelic imbalance occurred at these loci in the corresponding carcinomas.
