Oliveira Cristiane, Lourenço Gustavo Jacob, Rinck-Junior José Augusto, de Moraes Aparecida Machado, Lima Carmen Silvia Passos
Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Rua Alexander Fleming, 181, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP 13083-970, Brazil.
Med Oncol. 2017 Feb;34(2):19. doi: 10.1007/s12032-016-0868-z. Epub 2017 Jan 3.
Cutaneous melanoma (CM) cells are resistant to apoptosis, and steroid hormones are involved in this process through regulation of TP53, MDM2, BAX, and BCL2 expression. We analyzed herein sex differences in outcomes of CM patients associated with TP53 c.215G>C, MDM2 c.309T>G, BAX c.-248G>A, and BCL2 c.-717C>A polymorphisms. DNA from 121 men and 116 women patients was analyzed by polymerase chain reaction and enzymatic digestion assays. At 60 months of follow-up, shorter progression-free survival (PFS) was seen in males with MDM2 GG + BCL2 AA (20.0 vs. 62.6%, P = 0.0008) genotype. Men carriers of the genotype had poor PFS (HR 3.78, 95% CI 1.30-11.0) than others. For women, shorter PFS was associated with TP53 GC or CC (61.4 vs. 80.8%, P = 0.01) and TP53 GC or CC + MDM2 TG or GG (59.1 vs. 85.4%, P = 0.01) genotypes at the same time. Women carriers of the genotypes had poor PFS (HR 2.46, 95% CI 1.19-5.09; HR 9.49, 95% CI 1.14-78.50) than others, respectively. Our data present, for the first time, preliminary evidence that inherited abnormalities on TP53, MDM2 and BCL2 genes, enrolled in apoptosis pathways, have a pivotal role in differences of outcomes in women and men with CM.
皮肤黑色素瘤（CM）细胞对凋亡具有抗性，类固醇激素通过调节TP53、MDM2、BAX和BCL2的表达参与这一过程。我们在此分析了与TP53 c.215G>C、MDM2 c.309T>G、BAX c.-248G>A和BCL2 c.-717C>A多态性相关的CM患者预后的性别差异。通过聚合酶链反应和酶切分析对121名男性和116名女性患者的DNA进行了分析。在60个月的随访中，MDM2 GG + BCL2 AA（20.0%对62.6%，P = 0.0008）基因型的男性无进展生存期（PFS）较短。该基因型的男性携带者的PFS比其他人差（风险比3.78，95%置信区间1.30 - 11.0）。对于女性，较短的PFS同时与TP53 GC或CC（61.4%对80.8%，P = 0.01）以及TP53 GC或CC + MDM2 TG或GG（59.1%对85.4%，P = 0.01）基因型相关。这些基因型的女性携带者的PFS分别比其他人差（风险比2.46，95%置信区间1.19 - 5.09；风险比9.49，95%置信区间1.14 - 78.50）。我们的数据首次提供了初步证据，表明参与凋亡途径的TP53、MDM2和BCL2基因的遗传异常在CM女性和男性的预后差异中起关键作用。
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