Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Prostate. 2013 May;73(6):634-41. doi: 10.1002/pros.22604. Epub 2012 Nov 5.
Prostate cancer (PC) is the most frequently diagnosed non-skin malignancy in men in the Western world, yet few disease-associated mutations have been found. Recently, a low frequency recurring mutation in the HOXB13 gene was reported among both hereditary PC families and men from the general population.
We determined the distribution and frequency of the G84E HOXB13 variant in 1,310 incipient PC cases and 1,259 age-mated controls from a population-based, case-control study of PC.
The G84E mutation was more frequent in cases than controls (1.3% vs. 0.4%, respectively), and men with the HOXB13 G84E variant had a 3.3-fold higher relative risk of PC compared with noncarriers (95% CI, 1.21-8.96). There was a stronger association between the G84E variant and PC among men with no first-degree relative with PC (OR, 4.04; 95% CI, 1.12-14.51) compared to men with a family history of PC (OR, 1.49; 95% CI, 0.30-7.50; P = 0.36 for interaction). We observed some evidence of higher risk estimates associated with the variant for men with higher versus lower Gleason score (OR, 4.13; 95% CI, 1.38-12.38 vs. OR, 2.71; 95% CI, 0.88-8.30), and advanced versus local stage (OR, 4.47; 95% CI, 1.28-15.57 vs. OR, 2.98; 95% CI, 1.04-8.49), however these differences were not statistically different.
These results confirm the association of a rare HOXB13 mutation with PC in the general population and suggest that this variant may be associated with features of more aggressive disease.
在西方世界，前列腺癌（PC）是男性中最常见的非皮肤恶性肿瘤，但发现的与疾病相关的突变很少。最近，在遗传性 PC 家族和普通人群中的男性中，HOXB13 基因中出现了一种低频反复突变。
我们在一项基于人群的 PC 病例对照研究中，确定了 1310 例初发 PC 病例和 1259 例年龄匹配对照中 HOXB13 G84E 变体的分布和频率。
突变在病例中比对照组更常见（分别为 1.3%和 0.4%），携带 HOXB13 G84E 变体的男性患 PC 的相对风险是未携带者的 3.3 倍（95%CI，1.21-8.96）。与有家族史的 PC 男性相比，无一级亲属患有 PC 的男性中，G84E 变体与 PC 的相关性更强（OR，4.04；95%CI，1.12-14.51）。与家族史为 PC 的男性相比（OR，1.49；95%CI，0.30-7.50；P=0.36 交互作用），我们观察到该变体与 Gleason 评分较高的男性风险估计值较高的一些证据（OR，4.13；95%CI，1.38-12.38 与 OR，2.71；95%CI，0.88-8.30）和晚期与局部阶段（OR，4.47；95%CI，1.28-15.57 与 OR，2.98；95%CI，1.04-8.49），但这些差异无统计学意义。
这些结果证实了罕见的 HOXB13 突变与普通人群中 PC 的关联，并表明该变体可能与更具侵袭性疾病的特征相关。
