Influence of functional variants Asp312Asn and Lys751Gln of Xeroderma Pigmentosum Group D (XPD) and Glutathione S-transferase Mu 1 (GSTM1) and Theta 1 (GSTT1) genes on cutaneous melanoma susceptibility and prognosis

Exp Dermatol. 2019 May;28(5):631-635. doi: 10.1111/exd.13914.

Abstract

We aimed to evaluate whether variants in repair (XPD Asp312Asn, XPD Lys751Gln) and detoxification (GSTM1, GSTT1) genes alter risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Genotyping was performed in 229 CM patients and 258 controls. Individuals with XPD 312Asp/Asn or Asn/Asn plus GSTT1 null genotype were under 2.00 (95% CI: 1.06-3.79), and XPD 312Asn/Gln haplotype was under 1.44-fold (95% CI: 0.99-2.08) increased risks to CM than others. Individuals with GSTM1 plus GSTT1 null genotype had 9.61-fold (95% CI: 2.28-40.38) increased risk of metastatic CM. At 60 months of follow-up, patients with XPD 751Gln/Gln plus GSTT1 null and GSTM1 null plus GSTT1 null genotype presented 7.36 and 3.05 more chances of evolving to death in multivariate Cox analysis, respectively. In conclusion, our data indicate, for the first time, that specific variant combinations of XPD, GSTM1 and GSTT1 may increase susceptibility to CM and influence patients' clinicopathological features and survival.

Keywords: DNA repair; melanoma; polymorphism; prognosis; risk.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asparagine / genetics
  • Aspartic Acid / genetics
  • Cell Survival
  • Disease-Free Survival
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Glutamine / genetics
  • Glutathione Transferase / genetics*
  • Humans
  • Lysine / genetics
  • Melanoma / genetics*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Skin Neoplasms / genetics*
  • Treatment Outcome
  • Xeroderma Pigmentosum / diagnosis*
  • Xeroderma Pigmentosum / genetics*

Substances

  • Glutamine
  • Aspartic Acid
  • Asparagine
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Lysine

Supplementary concepts

  • Xeroderma Pigmentosum, Complementation Group D