Inherited NBN Mutations and Prostate Cancer Risk and Survival
Inherited NBN Mutations and Prostate Cancer Risk and Survival
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DOI：
10.4143/crt.2018.532
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发表时间：
2019-07-01
影响因子：
4.6
通讯作者：
Sasiadek, Maria Malgorzata
中科院分区：
文献类型：
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作者：
Rusak, Bogna;Kluzniak, Wojciech;Sasiadek, Maria Malgorzata
目的探讨NBN的4个创始等位基因对前列腺癌风险和生存的影响。材料与方法对5189名前列腺癌患者和6152名对照者进行了四种复发性NBN变异（657del5、R215W、I171V和E185Q）的基因分型。结果5189例未筛选病例中有74例检测到NBN 657del5突变，6152例对照中有35例检测到NBN 657del5突变（优势比[OR]为2.5;p < 0.001）。在657del5缺失携带者中，癌症风险仅限于具有相同基因的E185Q变体GG基因型的男性。在GG基因型男性中，与657del5相关的OR为4.4（95%可信区间[CI]， 2.4 - 8.0）。在其他E185Q基因型的男性中，与657del5相关的OR为1.4 (95% CI, 0.8 ~ 2.4)，相互作用显著（同质性p=0.006）。中位随访109个月后，657del5突变携带者的死亡率高于非携带者（风险比[HR]， 1.6; p=0.001）。657del5仅在E185Q为GG基因型的背景下对生存产生不良影响（HR, 1.9; p=0.0004）。结论nbn657del5基因突变与前列腺癌预后不良有关。这种突变的致病性，就前列腺癌的风险和生存而言，是由同一基因（E185Q）的错义变体修饰的。
PurposeThe purpose of this study was to establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival.Materials and MethodsFive thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q).ResultsThe NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004).ConclusionThe NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).