生物谷报道：科学家们最近发现了好几种前列腺癌的遗传风险因子，这使我们彻底了解了这种使美国黑人深受其害且在世界范围内居男性癌患首位的疾病的病因。三组研究人员在《自然-遗传学》杂志上公布了他们的研究结果，他们分别是哈佛大学和南加州大学的科学家组成其中一组，另一组由冰岛的解码基因公司组成，最后一组由美国国立卫生研究所的一部分国立癌症研究所组成。
研究人员之一，南加州大学Keck医学院的院长Brian Henderson博士在周日说到：“这项研究的重要性在于这是我们第一次发现了前列腺癌遗传基础的真正证据。”Henderson补充到：“这也是我们第一次洞察了这种疾病的病因，因此我们可以做一些相关的工作。”
研究中研究人员检验了数千位有或没有前列腺癌的男性的遗传信息。研究者们介绍了这七个遗传风险因子――一些人所含有的特殊的DNA序列而另外的人却没有――聚集在人类8号染色体上一个相对较小的区域，而且它们能够可靠的预测一个人患前列腺癌的概率有多大。其中的五个是最新发现的，其余两个证实了以前的发现。
研究者们说准确的找到这些遗传风险因子是向试图解释美国黑人比白人有更高的发病率方面迈出了重要的一步。黑人男性较之白人有两倍的危险死于这种疾病，而且在这项研究中几乎所有的风险因子在黑人中出现的频率更高。Henderson说黑人中这种疾病的高发病率在某种程度上暗示了这种疾病应该存在遗传基础。
研究人员说通过寻找一个人是否具有遗传风险因子，这项研究结果可以衍生出为具有高危险的人进行分类的方法，从而能够对这种疾病进行早期诊断。
Figure 1. Schematic view of the linkage and association results, marker density and LD structure in a region on chromosome 8q24.21.
(a) Linkage scan results for chromosome 8q from 871 Icelandic individuals with prostate cancer in 323 extended families (see ref. 3 for a detailed description). The interval between the two dashed horizontal lines corresponds to the admixture signal reported by ref. 4 that is associated with prostate cancer. (b) Single-marker (blue circles), two-marker (red circles) and LD-block haplotype (green circles) association results for all Icelandic individuals with prostate cancer (n = 1,453), using 1,660 SNPs from the HumanHap300 chip along with marker rs16901979, distributed over a 10-Mb region. Shown are P values <0.1, corrected for relatedness. (c) Association results from b, shown in greater detail, for a 1.4-Mb interval on 8q24.21. Filled black circles represent all 225 SNPs used in the association analysis of the 1.4-Mb interval, and the orange boxes denote the recombination hotspots (see main text for details). (d) Pairwise correlation coefficient (r 2) from the CEU HapMap population for the 1.4-Mb region in c; the blue boxes at the bottom indicate the location of the FAM84B (NSE2), AF268618 (POU5FLC20) and MYC (c-MYC) genes and the AW183883 EST previously described3. A scale for r 2 is shown at right.
原文出处：
Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24
Julius Gudmundsson, Patrick Sulem, Andrei Manolescu, Laufey T Amundadottir, Daniel Gudbjartsson, Agnar Helgason, Thorunn Rafnar, Jon T Bergthorsson, Bjarni A Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R Benediktsdottir, Margret Jakobsdottir, Jianfeng Xu, Thorarinn Blondal, Jelena Kostic, Jielin Sun, Shyamali Ghosh, Simon N Stacey, Magali Mouy, Jona Saemundsdottir, Valgerdur M Backman, Kristleifur Kristjansson, Alejandro Tres, Alan W Partin, Marjo T Albers-Akkers, Javier Godino-Ivan Marcos, Patrick C Walsh, Dorine W Swinkels, Sebastian Navarrete, Sarah D Isaacs, Katja K Aben, Theresa Graif, John Cashy, Manuel Ruiz-Echarri, Kathleen E Wiley, Brian K Suarez, J Alfred Witjes, Mike Frigge, Carole Ober, Eirikur Jonsson, Gudmundur V Einarsson, Jose I Mayordomo, Lambertus A Kiemeney, William B Isaacs, William J Catalona, Rosa B Barkardottir, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong & Kari Stefansson
Published online: 01 April 2007 | doi:10.1038/ng1999
Abstract | Full text | PDF (255K) | Supplementary Information
Multiple regions within 8q24 independently affect risk for prostate cancer
Christopher A Haiman, Nick Patterson, Matthew L Freedman, Simon R Myers, Malcolm C Pike, Alicja Waliszewska, Julie Neubauer, Arti Tandon, Christine Schirmer, Gavin J McDonald, Steven C Greenway, Daniel O Stram, Loic Le Marchand, Laurence N Kolonel, Melissa Frasco, David Wong, Loreall C Pooler, Kristin Ardlie, Ingrid Oakley-Girvan, Alice S Whittemore, Kathleen A Cooney, Esther M John, Sue A Ingles, David Altshuler, Brian E Henderson & David Reich
Published online: 01 April 2007 | doi:10.1038/ng2015
Abstract | Full text | PDF (555K) | Supplementary Information
Genome-wide association study of prostate cancer identifies a second risk locus at 8q24
Meredith Yeager, Nick Orr, Richard B Hayes, Kevin B Jacobs, Peter Kraft, Sholom Wacholder, Mark J Minichiello, Paul Fearnhead, Kai Yu, Nilanjan Chatterjee, Zhaoming Wang, Robert Welch, Brian J Staats, Eugenia E Calle, Heather Spencer Feigelson, Michael J Thun, Carmen Rodriguez, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Fredrick R Schumacher, Edward Giovannucci, Walter C Willett, Geraldine Cancel-Tassin, Olivier Cussenot, Antoine Valeri, Gerald L Andriole, Edward P Gelmann, Margaret Tucker, Daniela S Gerhard, Joseph F Fraumeni Jr, Robert Hoover, David J Hunter, Stephen J Chanock & Gilles Thomas
Published online: 01 April 2007 | doi:10.1038/ng2022
Abstract | Full text | PDF (386K) | Supplementary Information
作者简介：
David Reich Lab
KARI STEFANSSON
Kari Stefansson, M.D., Dr. Med., is president and CEO of deCode Genetics in Reykjavik, Iceland. He was previously Professor of Neurology, Pathology (Neuropathology), and Neuroscience at Harvard Medical School, and Chief of the Division of Neuropathology at Beth Israel Hospital in Boston. Stefansson received both an M.D. and Dr. Med. from the School of Medicine at the University of Iceland. He trained in neurology and neuropathology at the University of Chicago where he joined the faculty in 1983; when he left the University in 1993 to join the faculty at Harvard, he was Professor of Neurology and Pathology (Neuropathology) and a member of the Committees on Immunology and Neurobiology.
deCode Genetics is a genomics company that searches for disease genes in the Icelandic population. Until recently, the understanding of the genetic basis of human disease was fairly limited and was confined to classic genetic diseases such as hemophilia and cystic fibrosis. Although research into genetic disease established the concept that certain DNA sequence variations could have a huge impact on individual health, this principle could not be extended to more mainstream diseases such as cancer or diabetes. With the advent of the DNA sequencing and mapping technologies (sequencing is the establishment of the order of nucleotides along a piece of DNA; mapping assigns an order to large genomic fragments so that they can be efficiently sequenced), scientists are now able to more closely study genetic variations between individuals.
The hunt for disease genes begins by choosing a target disease such as osteoporosis or schizophrenia, whose genetic contribution in unknown. Family groups are then identified in which these disease genes are statistically more prevalent than in the general populations. Blood samples are collected from these individuals and their DNA is analyzed in order to identify regions of the genome that are linked to the disease.
The Icelandic population offers an unparalleled opportunity to study disease genetics for the following reasons:
Genetically homogeneous population
Genealogy of population since 1800 available to deCode, including health records.
Broad representation of genetically based diseases, for example, certain cancers, Multiple Sclerosis and cardiovascular disease.
