一个国际研究小组11日报告说，他们发现了与恶性前列腺癌患病风险相关的基因变异。尽管这项成果的临床应用仍比较有限，但将来有潜力与其他患病风险因素一道用来尽早预测哪类男性更易患恶性前列腺癌。
在此之前，研究已确认有大批基因与前列腺癌发病相关。为进一步筛选与恶性前列腺癌相关的基因，研究人员对4849名已发生扩散的恶性前列腺癌患者以及12205名病情发展缓慢的前列腺癌患者的遗传信息进行了对比分析。结果发现，一种名为rs4054823的基因如果发生变异，患恶性前列腺癌的风险将提高25％。
这项研究成果11日发表在美国《国家科学院学报》网络版上。领导这一研究的美国韦克福雷斯特大学教授徐剑锋说，这项研究表明，人类基因组中的某些基因变异确实会提高男性患恶性癌的风险。如果将来能够发现更多患病风险因素，医生就能尽早确定男性患恶性前列腺癌的具体风险。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS January 11, 2010, doi: 10.1073/pnas.0914061107
Inherited genetic variant predisposes to aggressive but not indolent prostate cancer
Jianfeng Xua,b,1, Siqun Lilly Zhenga,b, Sarah D. Isaacsc, Kathleen E. Wileyc, Fredrik Wiklundd, Jielin Suna,b, A. Karim Kadera,e, Ge Lia,b, Lina D. Purcella,b, Seong-Tae Kima,b, Fang-Chi Hsua,b,f, P?r Statting, Jonas Hugossonh, Jan Adolfssoni, Patrick C. Walshc, Jeffrey M. Trentj, David Dugganj, John Carptenj, Henrik Gr?nbergd,1 and William B. Isaacsc,1
aCenter for Cancer Genomics;
bCenter for Human Genomics, and Departments of
eUrology and
fBiostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157;
cDepartment of Urology, Johns Hopkins Medical Institutions, Baltimore, MD 21205;
dDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden SE 171–77;
gDepartment of Surgical and Perioperative sciences, Urology and Andrology, Ume? University Hospital, Ume?, Sweden S-90187;
hDepartment of Urology, Sahlgrenska University Hospital, G?teborg, Sweden S-413 45;
iOncological Center, Department of Clinical Innovation and Technology, Karolinska Institutet, Stockholm, Sweden SE 171–77; and
j Translational Genomics Research Institute, Phoenix, AZ 85004
Autopsy studies suggest that most aging men will develop lesions that, if detected clinically, would be diagnosed as prostate cancer (PCa). Most of these cancers are indolent and remain localized; however, a subset of PCa is aggressive and accounts for more than 27,000 deaths in the United States annually. Identification of factors specifically associated with risk for more aggressive PCa is urgently needed to reduce overdiagnosis and overtreatment of this common disease. To search for such factors, we compared the frequencies of SNPs among PCa patients who were defined as having either more aggressive or less aggressive disease in four populations examined in the Genetic Markers of Susceptibility (CGEMS) study performed by the National Cancer Institute. SNPs showing possible associations with disease severity were further evaluated in an additional three independent study populations from the United States and Sweden. In total, we studied 4,829 and 12,205 patients with more and less aggressive disease, respectively. We found that the frequency of the TT genotype of SNP rs4054823 at 17p12 was consistently higher among patients with more aggressive compared with less aggressive disease in each of the seven populations studied, with an overall P value of 2.1 × 10?8 under a recessive model, exceeding the conservative genome-wide significance level. The difference in frequency was largest between patients with high-grade, non–organ-confined disease compared with those with low-grade, organ-confined disease. This study demonstrates that inherited variants predisposing to aggressive but not indolent PCa exist in the genome, and suggests that the clinical potential of such variants as potential early markers for risk of aggressive PCa should be evaluated.
