据3月26日《美国医学协会期刊》（JAMA）上的一则研究显示，那些携带某种特定类型纯合性（即具有2种完全相同拷贝的同一基因，它们分别遗传自父母亲）的人可能具有更大的罹患癌症的可能性。
在过去的研究中，文章的作者观察到生殖系（某个体的那些可以将其遗传物质传递给后代的细胞）杂合性（具有两个不同形式的某特定基因，它们分别来自父母亲）在癌症病人中与对照组相比，其发生率很低。这向人们提出了这样一个问题，即纯合性是否在癌症的易感性方面扮演着某种角色。
美国克里夫兰临床基金会的Charis Eng及其同事开展了一项研究，旨在确定一个携带三种不同类型实质肿瘤的大型病患人群中的生殖系杂合性的发生频率，并与以人群为基础的对照组的发生频率进行比较。这一研究包括将生殖系DNA及相应的肿瘤DNA进行基因分析，而肿瘤DNA是从385名罹患癌症的病人（147名乳腺癌病人、116名前列腺癌病人及122名头颈部癌症病人）体内分离出来的。
研究人员表示，“我们的数据来自三种（并在第四种肿瘤中同样得到证实）不同的实质肿瘤。与对照组相比，这些数据证明在某些特别遗传标记处的生殖系的纯合性与这些癌症具有相关性…重要的是，我们在一种不同类型的实质肿瘤（即肺癌）中独立地验证了我们的观测结果，即在与祖先匹配的对照人群比较时发现，癌症病例的生殖系纯合性的频率有所增加。”
文章的作者写道：“我们在这里所观测到的结果应该在这些实质性的肿瘤中进行验证，并且应该在其它类型恶性肿瘤中进行探索。如果我们的数据能够被充分独立地复制的话，那么除了高外显率癌症易感性基因之外，在未来的癌症风险评估及处理中，应考虑生殖系杂合性以低外显率等位基因方式存在于某些特定位点会增加罹患癌症的可能性。另外，如果我们知道在那些相同位点的生殖系纯合性/杂合性的相对发生频率的话，通过进一步的研究及精细的结构分析，我们有可能利用这些数据来预测在某一肿瘤的特定基因位点失去杂合性的可能性。”（来源：EurekAlert!中文版）
生物谷推荐原始出处：
（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.
