一個國際研究小組11日報告說,，他們發(fā)現(xiàn)了與惡性前列腺癌患病風(fēng)險相關(guān)的基因變異,。盡管這項成果的臨床應(yīng)用仍比較有限，但將來有潛力與其他患病風(fēng)險因素一道用來盡早預(yù)測哪類男性更易患惡性前列腺癌,。
在此之前,，研究已確認有大批基因與前列腺癌發(fā)病相關(guān)。為進一步篩選與惡性前列腺癌相關(guān)的基因,，研究人員對4849名已發(fā)生擴散的惡性前列腺癌患者以及12205名病情發(fā)展緩慢的前列腺癌患者的遺傳信息進行了對比分析,。結(jié)果發(fā)現(xiàn)，一種名為rs4054823的基因如果發(fā)生變異,，患惡性前列腺癌的風(fēng)險將提高25％,。
這項研究成果11日發(fā)表在美國《國家科學(xué)院學(xué)報》網(wǎng)絡(luò)版上。領(lǐng)導(dǎo)這一研究的美國韋克福雷斯特大學(xué)教授徐劍鋒說,，這項研究表明,，人類基因組中的某些基因變異確實會提高男性患惡性癌的風(fēng)險。如果將來能夠發(fā)現(xiàn)更多患病風(fēng)險因素,，醫(yī)生就能盡早確定男性患惡性前列腺癌的具體風(fēng)險,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
