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Medical Oncology

, 34:19 | Cite as

Polymorphisms in apoptosis-related genes in cutaneous melanoma prognosis: sex disparity

  • Cristiane Oliveira
  • Gustavo Jacob Lourenço
  • José Augusto Rinck-Junior
  • Aparecida Machado de Moraes
  • Carmen Silvia Passos LimaEmail author
Original Paper

Abstract

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.

Keywords

Cutaneous melanoma Apoptosis Genetic polymorphism Prognosis 

Notes

Acknowledgements

This study was funding by São Paulo Research Foundation (FAPESP) Grant Nos. #2009/12602-0 and #2010/18904-5.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests.

Ethical standard

The study was approved according to the institutional review board guidelines (number 424/2006) and according to the Declaration of Helsinki, where all subjects provided written informed consent.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Cristiane Oliveira
    • 1
  • Gustavo Jacob Lourenço
    • 1
  • José Augusto Rinck-Junior
    • 1
  • Aparecida Machado de Moraes
    • 1
  • Carmen Silvia Passos Lima
    • 1
    Email author
  1. 1.Department of Internal Medicine, Faculty of Medical SciencesUniversity of CampinasCampinasBrazil

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