Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Eur Urol. 2014 Jan;65(1):169-76. doi: 10.1016/j.eururo.2012.07.027. Epub 2012 Jul 20.
A rare but recurrent missense mutation (G84E, rs138213197) in the gene homeobox B13 (HOXB13) was recently reported to be associated with hereditary prostate cancer.
To explore the prevalence and penetrance of HOXB13 G84E in a general population.
DESIGN, SETTING, AND PARTICIPANTS: G84E and 14 additional HOXB13 polymorphisms were genotyped in two population-based, Swedish, case-control samples (Cancer of the Prostate in Sweden [CAPS] and Stockholm-1) comprising 4693 controls and 5003 prostate cancer cases. CAPS collected data on patients and population controls nationally between 2001 and 2003. Stockholm-1 collected data on biopsy-positive patients and biopsy-negative controls in the Stockholm area between 2005 and 2007.
The outcome was pathologically verified prostate cancer. Relative and absolute risks among HOXB13 G84E mutation carriers were explored, as was the combined impact on disease risk of G84E and a polygenic score based on 33 established, common, low-risk variants.
HOXB13 G84E was observed in 1.3% of population controls and was strongly associated with prostate cancer risk (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2-5.4; Stockholm-1: OR: 3.5; 95% CI, 2.4-5.2). The strongest association was observed for young-onset (OR: 8.6; 95% CI, 5.1-14.0) and hereditary (OR: 6.6; 95% CI, 3.3-12.0) prostate cancer. Haplotype analyses supported that G84E is a founder mutation. G84E carriers have an estimated 33% (95% CI, 23-46) cumulative risk to age 80 yr of prostate cancer, compared to 12% (95% CI, 11-13) among noncarriers. For G84E carriers within the top quartile of a polygenic score of established susceptibility variants, the cumulative risk was estimated at 48% (95% CI, 36-64).
HOXB13 G84E is prevalent in >1% of the Swedish population and is associated with a 3.5-fold increased risk of prostate cancer. One-third of G84E carriers will be diagnosed with prostate cancer, which has implications for surveillance in mutation carriers.
最近有研究报道，在家盒 B13（HOXB13）基因中存在一种罕见但反复出现的错义突变（G84E，rs138213197），与遗传性前列腺癌有关。
探索 HOXB13 G84E 在一般人群中的流行率和外显率。
设计、地点和参与者：在两个基于人群的瑞典病例对照样本（瑞典前列腺癌研究[CAPS]和斯德哥尔摩-1）中，对 G84E 和另外 14 种 HOXB13 多态性进行了基因分型，这两个样本包含 4693 名对照和 5003 名前列腺癌病例。CAPS 于 2001 年至 2003 年期间在全国范围内收集了患者和人群对照的数据。斯德哥尔摩-1 于 2005 年至 2007 年期间在斯德哥尔摩地区收集了活检阳性患者和活检阴性对照的数据。
结局是经病理证实的前列腺癌。探讨了 HOXB13 G84E 突变携带者的相对和绝对风险，以及 G84E 与基于 33 个已确立的常见低风险变异的多基因评分对疾病风险的综合影响。
在人群对照中观察到 HOXB13 G84E 占 1.3%，与前列腺癌风险强烈相关（CAPS：比值比[OR]：3.4；95%置信区间[CI]，2.2-5.4；斯德哥尔摩-1：OR：3.5；95% CI，2.4-5.2）。在发病年龄较轻（OR：8.6；95% CI，5.1-14.0）和遗传性（OR：6.6；95% CI，3.3-12.0）前列腺癌中观察到最强的相关性。单体型分析支持 G84E 是一个起源突变。与非携带者相比，G84E 携带者估计在 80 岁时累积患前列腺癌的风险为 33%（95% CI，23-46），而携带者为 12%（95% CI，11-13）。在已确立易感性变异的多基因评分最高四分位数的 G84E 携带者中，累积风险估计为 48%（95% CI，36-64）。
HOXB13 G84E 在瑞典人群中超过 1%，与前列腺癌风险增加 3.5 倍相关。三分之一的 G84E 携带者将被诊断为前列腺癌，这对突变携带者的监测有影响。
