Confirmation of the HOXB13 G84E germline mutation in familial prostate cancer.
Confirmation of the HOXB13 G84E germline mutation in familial prostate cancer.
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DOI：
10.1158/1055-9965.epi-12-0495
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Smith JR
中科院分区：
文献类型：
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作者：
Breyer JP;Avritt TG;McReynolds KM;Dupont WD;Smith JR
最近一项针对家族性和早发性前列腺癌的研究报告了欧洲血统男性中反复出现的罕见 HOXB13 种系突变。该基因位于 17q21 遗传性前列腺癌连锁区间内。我们在范德比尔特大学的一项家族性前列腺癌病例对照研究中评估了 HOXB13 的 G84E 种系突变 (rs138213197)，以独立评估该突变与家族性前列腺癌的关联。我们对 928 名家族性前列腺癌先证者和 930 名没有前列腺癌个人或家族史的对照先证者进行了基因分型。我们的研究证实了欧洲血统受试者中 HOXB13 的 G84E 突变与前列腺癌风险之间的关联。我们在 16 个家族病例和两个对照中观察到了突变，每个病例都是杂合子。突变携带者患前列腺癌的优势比为 7.9 (95% CI 1.8 – 34.5, P = 0.0062)。在所有家族病例先证者中，携带率为1.9%，在≥3个受影响家系的先证者中，携带率为2.7%。在一项由 268 名没有其他前列腺癌家族史的欧洲血统先证者组成的单独病例系列中，携带率为 1.5%。 HOXB13 的种系突变 G84E 是一种罕见但反复发生的突变，与欧洲血统男性患前列腺癌的风险升高相关，其效应大小大于先前在全基因组关联研究中验证的风险变异所观察到的效应大小。这项研究独立证实了种系 HOXB13 突变与家族性前列腺癌的关联。
A recent study of familial and early onset prostate cancer reported a recurrent rare germline mutation of HOXB13 among men of European descent. The gene resides within the 17q21 hereditary prostate cancer linkage interval. We evaluated the G84E germline mutation (rs138213197) of HOXB13 in a case-control study of familial prostate cancer at Vanderbilt University to independently evaluate the association of the mutation with familial prostate cancer. We genotyped 928 familial prostate cancer probands, and 930 control probands without a personal or family history of prostate cancer. Our study confirmed the association between the G84E mutation of HOXB13 and risk of prostate cancer among subjects of European descent. We observed the mutation in 16 familial cases and in two controls, each as heterozygotes. The odds ratio for prostate cancer was 7.9 (95% CI 1.8 – 34.5, P = 0.0062) among carriers of the mutation. The carrier rate was 1.9% among all familial case probands, and 2.7% among probands of pedigrees with ≥ 3 affected. In a separate case series of 268 probands of European descent with no additional family history of prostate cancer, the carrier rate was 1.5%. The germline mutation G84E of HOXB13 is a rare but recurrent mutation associated with elevated risk of prostate cancer in men of European descent, with an effect size that is greater than observed for previously validated risk variants of genome wide association studies. This study independently confirms the association of a germline HOXB13 mutation with familial prostate cancer.