Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients

Macarena Gomez Lira, Lisa Provezza, Giovanni Malerba, Luigi Naldi, Giuseppe Remuzzi, Luigino Boschiero, Alberto Forni, Carlo Rugiu, Stefano Piaserico, Mauro Alaibac, Alberto Turco, Giampiero Girolomoni, Gianpaolo Tessari

Research output: Contribution to journalArticlepeer-review

Abstract

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P =0.017]. Homozygosity for allele GSTP1 Val105 was lower in cases [OR 0.3 (0.1-0.8); P =0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P =0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A+B, OR 3.1 (1.4-6.8); P =0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val462 genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val462, show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P =0.03], especially SCC [OR 6.5 (1.4-34.4); P =0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val462 are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.

Original languageEnglish
Pages (from-to)958-965
Number of pages8
JournalExperimental Dermatology
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 2006

Keywords

  • CYP1A1
  • GlutathioneS-transferase
  • Non-melanomaskin cancer
  • Polymorphisms
  • Transplantrecipients

ASJC Scopus subject areas

  • Dermatology

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