Rennert Hanna, Zeigler-Johnson Charnita, Mittal Rama Devi, Tan Ying-cai, Sadowl Caren M, Edwards Joshua, Finley Matthew J, Mandhani Anil, Mital Balraj, Rebbeck Timothy R
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10021, USA.
Urology. 2008 Aug;72(2):456-60. doi: 10.1016/j.urology.2007.11.139. Epub 2008 Apr 24.
Prostate cancer (PC) varies widely by geographic location and ethnicity. American men have a high PC risk but most have localized disease. In contrast, Asian Indians have a low PC risk but most are diagnosed with metastatic disease. Epidemiological and genetic data suggest an important role of genetic susceptibility in PC. Most studies were performed in whites. Substantially less is known about gene variation-associated PC in low-risk populations. The objective of this study was to investigate the role of RNASEL and MSR1 in Asian-Indian men with advanced PC.
We genotyped DNA samples obtained from 113 cases and 245 age-matched controls (Northern India).
For RNASEL, we identified 8 variants (7 novel and 1 previously published, D541E), including 4 exonic, 3 intronic, and 1 change in the 3'-noncoding region. Of these, we detected a novel 4-bp truncation mutation (Val51ArgfsX2) in 2 controls. For MSR1, we identified 4 novel variants (2 intronic and 2 exonic) and 2 previously reported variants (P275A and promoter -4,637 A>G). We also genotyped 3 common MSR1 variations (promoter -14,742 A>G, IVS5-59 C>A, and IVS7 delinsTTA). We found no associations among any of the sequence variations and PC. Three major haplotypes account for most of all MSR1 haplotypes in Asian Indians. Haplotype frequencies were not significantly different between cases and controls.
Our results do not support a role for RNASEL, or MSR1 mutations in advanced Asian-Indian PC. This study warrants additional investigations of these genes in etiology particularly among individuals from diverse ethnic and geographic groups.
前列腺癌(PC)在地理位置和种族上差异很大。美国男性患PC的风险较高,但大多数为局限性疾病。相比之下,亚洲印度男性患PC的风险较低,但大多数被诊断为转移性疾病。流行病学和遗传学数据表明遗传易感性在PC中起重要作用。大多数研究是在白人中进行的。对于低风险人群中与基因变异相关的PC了解甚少。本研究的目的是调查RNASEL和MSR1在患有晚期PC的亚洲印度男性中的作用。
我们对从113例患者和245例年龄匹配的对照(印度北部)获得的DNA样本进行了基因分型。
对于RNASEL,我们鉴定出8个变异(7个新变异和1个先前发表的D541E),包括4个外显子变异、3个内含子变异和1个3'-非编码区的变化。其中,我们在2例对照中检测到一个新的4碱基截断突变(Val51ArgfsX2)。对于MSR1,我们鉴定出4个新变异(2个内含子变异和2个外显子变异)和2个先前报道的变异(P275A和启动子-4637 A>G)。我们还对3个常见的MSR1变异(启动子-14742 A>G、IVS5-59 C>A和IVS7 delinsTTA)进行了基因分型。我们发现任何序列变异与PC之间均无关联。三个主要单倍型占亚洲印度人所有MSR1单倍型的大部分。病例组和对照组之间的单倍型频率无显著差异。
我们的结果不支持RNASEL或MSR1突变在晚期亚洲印度人PC中起作用。本研究有必要对这些基因在病因学方面进行进一步研究,特别是在来自不同种族和地理群体的个体中。