Xu Jianfeng, Sun Jielin, Kader A Karim, Lindström Sara, Wiklund Fredrik, Hsu Fang-Chi, Johansson Jan-Erik, Zheng S Lilly, Thomas Gilles, Hayes Richard B, Kraft Peter, Hunter David J, Chanock Stephen J, Isaacs William B, Grönberg Henrik
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Prostate. 2009 Oct 1;69(14):1565-72. doi: 10.1002/pros.21002.
Multiple DNA sequence variants in the form of single-nucleotide polymorphisms (SNPs) have been found to be reproducibly associated with prostate cancer (PCa) risk.
Absolute risk for PCa among men with various numbers of inherited risk alleles and family history of PCa was estimated in a population-based case-control study in Sweden (2,893 cases and 1,781 controls), and a nested case-control study from the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial in the U.S. (1,172 cases and 1,157 controls).
Increased number of risk alleles and positive family history were independently associated with PCa risk. Considering men with 11 risk alleles (mode) and negative family history as having baseline risk, men who had >or=14 risk alleles and positive family history had an odds ratio (OR) of 4.92 [95% confidence interval (CI): 3.64-6.64] in the Swedish study. These associations were confirmed in the U.S. population. Once a man's SNP genotypes and family history are known, his absolute risk for PCa can be readily calculated and easily interpreted. For example, 55-year-old men with a family history and >or=14 risk alleles have a 52% and 41% risk of being diagnosed with PCa in the next 20 years in the Swedish and U.S. populations, respectively. In comparison, without knowledge of genotype and family history, these men had an average population absolute risk of 13%.
This risk prediction model may be used to identify men at considerably elevated PCa risk who may be selected for chemoprevention.
已发现多种单核苷酸多态性（SNP）形式的DNA序列变异与前列腺癌（PCa）风险存在可重复性关联。
在瑞典一项基于人群的病例对照研究（2893例病例和1781例对照）以及美国前列腺、肺、结肠和卵巢（PLCO）癌症筛查试验的巢式病例对照研究（1172例病例和1157例对照）中，估计了具有不同数量遗传风险等位基因和PCa家族史男性患PCa的绝对风险。
风险等位基因数量增加和家族史阳性与PCa风险独立相关。在瑞典的研究中，将具有11个风险等位基因（众数）且家族史阴性的男性视为具有基线风险，那么具有≥14个风险等位基因且家族史阳性的男性的优势比（OR）为4.92[95%置信区间（CI）：3.64 - 6.64]。这些关联在美国人群中得到了证实。一旦了解了男性的SNP基因型和家族史，其患PCa的绝对风险就能很容易地计算出来并易于解读。例如，在瑞典和美国人群中，有家族史且≥14个风险等位基因的55岁男性在未来20年被诊断为PCa的风险分别为52%和41%。相比之下，在不了解基因型和家族史的情况下，这些男性的平均人群绝对风险为13%。
这种风险预测模型可用于识别PCa风险显著升高的男性，这些男性可能会被选作化学预防的对象。
