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

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.