生物谷報道：科學(xué)家們最近發(fā)現(xiàn)了好幾種前列腺癌的遺傳風(fēng)險因子，這使我們徹底了解了這種使美國黑人深受其害且在世界范圍內(nèi)居男性癌患首位的疾病的病因,。三組研究人員在《自然-遺傳學(xué)》雜志上公布了他們的研究結(jié)果，他們分別是哈佛大學(xué)和南加州大學(xué)的科學(xué)家組成其中一組,，另一組由冰島的解碼基因公司組成，最后一組由美國國立衛(wèi)生研究所的一部分國立癌癥研究所組成,。
研究人員之一,，南加州大學(xué)Keck醫(yī)學(xué)院的院長Brian Henderson博士在周日說到：“這項研究的重要性在于這是我們第一次發(fā)現(xiàn)了前列腺癌遺傳基礎(chǔ)的真正證據(jù)。”Henderson補(bǔ)充到：“這也是我們第一次洞察了這種疾病的病因,，因此我們可以做一些相關(guān)的工作。”
研究中研究人員檢驗了數(shù)千位有或沒有前列腺癌的男性的遺傳信息,。研究者們介紹了這七個遺傳風(fēng)險因子――一些人所含有的特殊的DNA序列而另外的人卻沒有――聚集在人類8號染色體上一個相對較小的區(qū)域,，而且它們能夠可靠的預(yù)測一個人患前列腺癌的概率有多大。其中的五個是最新發(fā)現(xiàn)的,，其余兩個證實了以前的發(fā)現(xiàn),。
研究者們說準(zhǔn)確的找到這些遺傳風(fēng)險因子是向試圖解釋美國黑人比白人有更高的發(fā)病率方面邁出了重要的一步。黑人男性較之白人有兩倍的危險死于這種疾病,，而且在這項研究中幾乎所有的風(fēng)險因子在黑人中出現(xiàn)的頻率更高,。Henderson說黑人中這種疾病的高發(fā)病率在某種程度上暗示了這種疾病應(yīng)該存在遺傳基礎(chǔ)。
研究人員說通過尋找一個人是否具有遺傳風(fēng)險因子,，這項研究結(jié)果可以衍生出為具有高危險的人進(jìn)行分類的方法,，從而能夠?qū)@種疾病進(jìn)行早期診斷。
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.
原文出處：
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
作者簡介：
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.
