英国和美国两个科研小组分别在新一期《自然遗传学》杂志上宣布，他们发现了导致睾丸癌的基因变异。这是医学界第一次找到睾丸癌的遗传致病因素。
英国癌症研究所科研小组报告说，他们比较了730名睾丸癌患者和健康男性的基因组信息，发现分别位于5号、6号和12号染色体内的3个基因，无论哪一个发生变异，人患睾丸癌的风险都会显著增加。如果3个基因均变异，那么患睾丸癌的风险会高达健康男性的4倍。
美国宾夕法尼亚大学医学院科研小组发现的是其中的两个基因变异。两个研究小组在《自然遗传学》上介绍说，他们将继续进行“基因搜查”，寻找与睾丸癌有关的更多的基因变异。
睾丸癌是中青年男性最常见的癌症之一，大多数都可以治愈。英美科学家的研究成果将有助于开发针对睾丸癌的更好的治疗方法。此外，借助基因诊断，医学研究人员将来有望早期筛查出睾丸癌患病风险高的人，大大提高早期诊断和预防的效率。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics 31 May 2009 | doi:10.1038/ng.394
A genome-wide association study of testicular germ cell tumor
Elizabeth A Rapley1, Clare Turnbull1, Ali Amin Al Olama2, Emmanouil T Dermitzakis3, Rachel Linger1, Robert A Huddart4, Anthony Renwick1, Deborah Hughes1, Sarah Hines1, Sheila Seal1, Jonathan Morrison2, Jeremie Nsengimana5, Panagiotis Deloukas3, The UK Testicular Cancer Collaboration6, Nazneen Rahman1, D Timothy Bishop5, Douglas F Easton2 & Michael R Stratton1,3
We conducted a genome-wide association study for testicular germ cell tumor (TGCT), genotyping 307,666 SNPs in 730 cases and 1,435 controls from the UK and replicating associations in a further 571 cases and 1,806 controls. We found strong evidence for susceptibility loci on chromosome 5 (per allele OR = 1.37 (95% CI = 1.19–1.58), P = 3 10-13), chromosome 6 (OR = 1.50 (95% CI = 1.28–1.75), P = 10-13) and chromosome 12 (OR = 2.55 (95% CI = 2.05–3.19), P = 10-31). KITLG, encoding the ligand for the receptor tyrosine kinase KIT, which has previously been implicated in the pathogenesis of TGCT and the biology of germ cells, may explain the association on chromosome 12.
1 Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
2 Cancer Research UK, Genetic Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK.
3 The Wellcome Trust Sanger Institute, Hinxton, UK.
4 Academic Radiotherapy Unit, Institute of Cancer Research, Sutton, Surrey, UK.
5 Section of Epidemiology & Biostatistics, Leeds Institute of Molecular Medicine, Leeds, UK.
6 A full list of members is listed in the Supplementary Note online.
Nature Genetics 31 May 2009 | doi:10.1038/ng.393
Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer
Peter A Kanetsky1,2, Nandita Mitra1,2, Saran Vardhanabhuti1, Mingyao Li1, David J Vaughn2,3, Richard Letrero2,4, Stephanie L Ciosek2,4, David R Doody5, Lauren M Smith4, JoEllen Weaver6, Anthony Albano7, Chu Chen5,8, Jacqueline R Starr5,8,9, Daniel J Rader10,11, Andrew K Godwin6, Muredach P Reilly10,11, Hakon Hakonarson7, Stephen M Schwartz5,8 & Katherine L Nathanson2,4
Testicular germ cell tumors (TGCT) have been expected to have a strong underlying genetic component. We conducted a genome-wide scan among 277 TGCT cases and 919 controls and found that seven markers at 12p22 within KITLG (c-KIT ligand) reached genome-wide significance (P < 5.0 10-8 in discovery). In independent replication, TGCT risk was increased threefold per copy of the major allele at rs3782179 and rs4474514 (OR = 3.08, 95% CI = 2.29–4.13; OR = 3.07, 95% CI = 2.29–4.13, respectively). We found associations with rs4324715 and rs6897876 at 5q31.3 near SPRY4 (sprouty 4; P < 5.0 10-6 in discovery). In independent replication, risk of TGCT was increased nearly 40% per copy of the major allele (OR = 1.37, 95% CI = 1.14–1.64; OR = 1.39, 95% CI = 1.16–1.66, respectively). All of the genotypes were associated with both seminoma and nonseminoma TGCT subtypes. These results demonstrate that common genetic variants affect TGCT risk and implicate KITLG and SPRY4 as genes involved in TGCT susceptibility.
1 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
2 Abramson Cancer Center, Divisions of Hematology-Oncology and Medical Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
3 Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
4 Division of Medical Genetics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
5 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
6 Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
7 Center for Applied Genomics and Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
8 Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
9 Department of Pediatrics, School of Medicine, University of Washington, Seattle, Washington, USA.
10 Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
11 Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
